Trial Outcomes & Findings for Adalimumab vs. Conventional Immunosuppression for Uveitis Trial (NCT NCT03828019)

NCT ID: NCT03828019

Last Updated: 2025-05-16

Results Overview

Corticosteroid-sparing success is defined as achieving inactive uveitis for two consecutive visits \>= 28 days apart while on \<= 7.5 mg/day of corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging. Steroid dose and uveitis activity from visit months 6,8,10 and 12 were included in the analysis. Generalized estimating equations were used to fit logistic regression models to compare the cumulative proportion of corticosteroid sparing between the two treatment groups over time while accounting for correlation between replicate measurements on the same individual with an unstructured covariance matrix. Results were reported at 6 months (primary outcome) and 12 months (secondary outcome).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 227 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2025-05-16

Participant Flow

Unit of analysis: Eyes with uveitis

Participant milestones

Measure	Adalimumab (ADA) Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to tumor necrosis factor (TNF-α), which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CIN) Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm twice a day (BID); max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Overall Study STARTED	114 214	113 220
Overall Study Primary Outcome 6 Months	112 211	105 204
Overall Study COMPLETED	109 206	98 190
Overall Study NOT COMPLETED	5 8	15 30

Reasons for withdrawal

Measure	Adalimumab (ADA) Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to tumor necrosis factor (TNF-α), which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CIN) Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm twice a day (BID); max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Overall Study Withdrawal by Subject	3	8
Overall Study Lost to Follow-up	1	6
Overall Study Incarcerated	1	0
Overall Study Adverse Event	0	1

Baseline Characteristics

Adalimumab vs. Conventional Immunosuppression for Uveitis Trial

Baseline characteristics by cohort

Measure	Adalimumab (ADA) n=214 Eyes with uveitis Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=220 Eyes with uveitis Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.	Total n=434 Eyes with uveitis Total of all reporting groups
Age, Continuous	44 years n=5 Participants	44 years n=7 Participants	44 years n=5 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	78 Participants n=7 Participants	153 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	35 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	15 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	96 Participants n=5 Participants	98 Participants n=7 Participants	194 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	4 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	21 Participants n=5 Participants	20 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) White	81 Participants n=5 Participants	82 Participants n=7 Participants	163 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Region of Enrollment United States	91 Participants n=5 Participants	101 Participants n=7 Participants	192 Participants n=5 Participants
Region of Enrollment United Kingdom	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Region of Enrollment Australia	14 Participants n=5 Participants	9 Participants n=7 Participants	23 Participants n=5 Participants
Duration of uveitis at baseline	0.9 years n=5 Participants	0.9 years n=7 Participants	0.9 years n=5 Participants
Uveitis diagnostic class at baseline Intermediate	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Uveitis diagnostic class at baseline Anterior and intermediate uveitis	20 Participants n=5 Participants	12 Participants n=7 Participants	32 Participants n=5 Participants
Uveitis diagnostic class at baseline Birdshot chorioretinitis	23 Participants n=5 Participants	26 Participants n=7 Participants	49 Participants n=5 Participants
Uveitis diagnostic class at baseline Multifocal choroiditis with panuveitis	10 Participants n=5 Participants	9 Participants n=7 Participants	19 Participants n=5 Participants
Uveitis diagnostic class at baseline Serpiginous choroiditis	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Uveitis diagnostic class at baseline Punctate inner choroiditis	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Uveitis diagnostic class at baseline Sympathetic ophthalmia	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Uveitis diagnostic class at baseline Vogt-Koyanagi-Harada disease early stage	7 Participants n=5 Participants	6 Participants n=7 Participants	13 Participants n=5 Participants
Uveitis diagnostic class at baseline Vogt-Koyanagi-Harada disease late stage	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Uveitis diagnostic class at baseline Isolated retinal vasculitis or panuveitis with retinal vasculitis	28 Participants n=5 Participants	23 Participants n=7 Participants	51 Participants n=5 Participants
Uveitis diagnostic class at baseline Isolated choroiditis or panuveitis with choroiditis	10 Participants n=5 Participants	15 Participants n=7 Participants	25 Participants n=5 Participants
NEI-VFQ-25	72 units on a scale n=5 Participants	73 units on a scale n=7 Participants	73 units on a scale n=5 Participants
EQ-5D health related quality of life	0.93 units on a scale n=5 Participants	0.84 units on a scale n=7 Participants	0.85 units on a scale n=5 Participants
Short-Form Health Survey- 36 item Physical component	52 units on a scale n=5 Participants	54 units on a scale n=7 Participants	54 units on a scale n=5 Participants
Short-Form Health Survey- 36 item Mental component	53 units on a scale n=5 Participants	52 units on a scale n=7 Participants	52 units on a scale n=5 Participants
Best Corrected Visual Acuity (BCVA)	81 Standard letters EDTRS eye chart n=5 Participants	81 Standard letters EDTRS eye chart n=7 Participants	81 Standard letters EDTRS eye chart n=5 Participants
Eye lens status Eye is phakic ( natural lens) with no opacity	102 Eyes with uveitis n=214 Eyes with uveitis	87 Eyes with uveitis n=220 Eyes with uveitis	189 Eyes with uveitis n=434 Eyes with uveitis
Eye lens status Eye is phakic (natural lens) with opacity/cataract	76 Eyes with uveitis n=214 Eyes with uveitis	89 Eyes with uveitis n=220 Eyes with uveitis	165 Eyes with uveitis n=434 Eyes with uveitis
Eye lens status Eye is pseudophakic (Interocular lens placed)	33 Eyes with uveitis n=214 Eyes with uveitis	42 Eyes with uveitis n=220 Eyes with uveitis	75 Eyes with uveitis n=434 Eyes with uveitis
Eye lens status Eye is aphakic (natural lens removed)	3 Eyes with uveitis n=214 Eyes with uveitis	2 Eyes with uveitis n=220 Eyes with uveitis	5 Eyes with uveitis n=434 Eyes with uveitis
Retinal thickness at the center subfield	255 um n=214 Eyes with uveitis	247 um n=220 Eyes with uveitis	252 um n=434 Eyes with uveitis
Immunotherapy at baseline On no immunotherapy at baseline	90 Participants n=5 Participants	88 Participants n=7 Participants	178 Participants n=5 Participants
Immunotherapy at baseline On one immunotherapy drug at baseline	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
On corticosteroids greater than of equal to 30 mg at baseline On less than 30 mg corticosteroids	29 Participants n=5 Participants	27 Participants n=7 Participants	56 Participants n=5 Participants
On corticosteroids greater than of equal to 30 mg at baseline On greater than or equal to 30 mg corticosteriods	85 Participants n=5 Participants	85 Participants n=7 Participants	170 Participants n=5 Participants
On corticosteroids greater than of equal to 30 mg at baseline missing steroid treatment data at BL	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: Participants with follow-up data through the 6 month visit or had an event (corticosteroid sparing success) before they were lost to follow-up

Corticosteroid-sparing success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart while on <= 7.5 mg/day of corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging. Steroid dose and uveitis activity from visit months 6,8,10 and 12 were included in the analysis. Generalized estimating equations were used to fit logistic regression models to compare the cumulative proportion of corticosteroid sparing between the two treatment groups over time while accounting for correlation between replicate measurements on the same individual with an unstructured covariance matrix. Results were reported at 6 months (primary outcome) and 12 months (secondary outcome).

Outcome measures

Measure	Adalimumab (ADA) n=112 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=105 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Corticosteroid-sparing Treatment Success Within the First 6 Months After Randomization	0.69 Cumulative proportion of participants Interval 0.6 to 0.77	0.54 Cumulative proportion of participants Interval 0.44 to 0.64

SECONDARY outcome

Timeframe: 12 months

Population: Participants with follow-up data through the 12 month visit or had an event (corticosteroid sparing success) before they were lost to follow-up

Corticosteroid-sparing success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart while on <= 7.5 mg/day of corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging. Steroid dose and uveitis activity from visit months 6,8,10 and 12 were included in the analysis. Generalized estimating equations were used to fit logistic regression models to compare the cumulative proportion of corticosteroid sparing between the two treatment groups over time while accounting for correlation between replicate measurements on the same individual with an unstructured covariance matrix. Results were reported at 6 months (primary outcome) and 12 months (secondary outcome).

Outcome measures

Measure	Adalimumab (ADA) n=111 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=100 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Corticosteroid-sparing Treatment Success Within the First 12 Months After Randomization	0.86 Cumulative proportion of participants Interval 0.78 to 0.92	0.77 Cumulative proportion of participants Interval 0.67 to 0.84

SECONDARY outcome

Timeframe: 6 months

Population: Participants with follow-up through the 6 months visit or had an event (discontinued corticosteroids) before lost to follow-up

Corticosteroid discontinuation success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart after discontinuing corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging. Steroid dose and uveitis activity from visit months 6,8,10 and 12 were included in the analysis. Generalized estimating equations were used to fit logistic regression models to compare the cumulative proportion of corticosteroid discontinuation between the two treatment groups over time while accounting for correlation between replicate measurements on the same individual with an unstructured covariance matrix. Results were reported at 6 months and 12 months.

Outcome measures

Measure	Adalimumab (ADA) n=112 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=105 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Corticosteroid Discontinuation Success by 6 Months	0.15 Cumulative proportion of participants Interval 0.09 to 0.24	0.11 Cumulative proportion of participants Interval 0.06 to 0.18

SECONDARY outcome

Timeframe: 12 months

Corticosteroid discontinuation success is defined as achieving inactive uveitis for two consecutive visits >= 28 days apart after discontinuing corticosteroids. Uveitis status (active vs inactive) is determined by the study ophthalmologist after reviewing the eye exam and imaging. Steroid dose and uveitis activity from visit months 6,8,10 and 12 were included in the analysis. Generalized estimating equations were used to fit logistic regression models to compare the cumulative proportion of corticosteroid discontinuation between the two treatment groups over time while accounting for correlation between replicate measurements on the same individual with an unstructured covariance matrix. Results were reported at 6 months and 12 months.

Outcome measures

Measure	Adalimumab (ADA) n=109 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=98 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Corticosteroid Discontinuation Success by 12 Months	0.55 Cumulative proportion of participants Interval 0.45 to 0.64	0.40 Cumulative proportion of participants Interval 0.3 to 0.5

SECONDARY outcome

Timeframe: 12 months

Population: Participants with follow up treatment data

Corticosteroid dose was collected at baseline and months 1,2,3,4,5,6,8,10, and 12. Mean corticosteroid dose per day was estimated with a negative binomial model at 12 months.

Outcome measures

Measure	Adalimumab (ADA) n=113 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Corticosteroid Exposure Over 12 Months	11.8 mg/day of steroid use over 12 months Interval 10.5 to 13.2	13.8 mg/day of steroid use over 12 months Interval 12.3 to 15.4

SECONDARY outcome

Timeframe: 12 months

Population: All participants

Mean change in best-corrected visual acuity from baseline to 12 months. Participants' visual acuity was measured by certified examiners with best refractive correction in place. Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity (85 letters is 20/20 vision). Visual acuity data was collected at baseline and months 1,2,3,4,5,6,8,10, and 12 and estimated at 12 months with a mixed model.

Outcome measures

Measure	Adalimumab (ADA) n=212 Eyes with uveitis Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=214 Eyes with uveitis Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Best Corrected Visual Acuity Change at 12 Months	3.6 Standard letters ETDRS eye chart Interval 1.3 to 5.8	3.2 Standard letters ETDRS eye chart Interval 1.7 to 4.6

SECONDARY outcome

Timeframe: 12 months

Population: Participants with follow up retinal thickness data at enrollment and the 12 month visit

Macular edema is defined as central retinal thickness greater than or equal to 300 micrometers as measured by a masked grader's review of OCT images. Greater retinal thickness is associated with poorer vision. Outcome measure is the odds ratio comparing macular edema at 12 months to baseline macular edema. Macular edema was measured at baseline and months 3, 6, and 12. The odds ratio at 12 months was estimated with a mixed model.

Outcome measures

Measure	Adalimumab (ADA) n=198 Eyes with uveitis Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=188 Eyes with uveitis Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Macular Edema Over 12 Months of Follow up	0.34 Odds ratio Interval 0.23 to 0.51	0.63 Odds ratio Interval 0.42 to 0.94

SECONDARY outcome

Timeframe: 12 months

Population: Participants with follow up after the baseline visit

Incidence of infections over 12 months of follow-up. Participants were asked about occurrences since the previous visit of infections requiring antibiotic or antiviral treatment. Data was collected at months 1,2,3,4,5,6,8,10, and 12. The rate of infections at 12 months was estimated with a negative binomial model.

Outcome measures

Measure	Adalimumab (ADA) n=113 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Incidence of Infections at 12 Months	0.40 Number of infections per person year Interval 0.27 to 0.61	0.37 Number of infections per person year Interval 0.24 to 0.57

SECONDARY outcome

Timeframe: 12 months

Population: Participants with follow-up that did not have elevated levels of AST or ALT at baseline

Cumulative percent of participants having elevated levels of aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than twice the upper level of normal by 12 months. Elevated levels of AST and ALT may indicate decline in liver function. Lab values of AST and ALT were measured at baseline and months 1,2,3,4,5,6,8,10, and 12 and the cumulative percent of participants with elevated lab values by 12 months was estimated by Kaplan Meier methods.

Outcome measures

Measure	Adalimumab (ADA) n=111 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Elevated Levels of AST or ALT (Hepatoxicity) by 12 Months.	2 Cumulative percent of participants Interval 0.0 to 5.0	10 Cumulative percent of participants Interval 4.0 to 16.0

SECONDARY outcome

Timeframe: 12 months

Population: Participants with follow-up that did not have elevated creatine at the time of enrollment

Cumulative percent of participants having elevated creatine values (creatine greater than 30% above baseline or creatine > 1.5 mg/dL) by 12 months. Increases in creatine levels may indicate decreased kidney function. Lab values of creatine were measured at baseline and months 1,2,3,4,5,6,8,10, and 12 and the cumulative percent of participants with elevated creatine at 12 months was estimated by Kaplan Meier methods.

Outcome measures

Measure	Adalimumab (ADA) n=111 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Elevated Creatine (Nephrotoxicity) by 12 Months	13 Cumulative percent of participants Interval 6.0 to 18.0	14 Cumulative percent of participants Interval 7.0 to 20.0

SECONDARY outcome

Timeframe: 12 months

The EQ-5D (EuroQol Group - 5 Dimension questionnaire) is a participant reported validated questionnaire that measures the patient's health status in five dimensions of health: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. The range of questionnaire index scores is -0.59 to 1 where score of 1 indicates best possible health. The outcome measure is the odds of having EQ-5D score of 1 (perfect health) at 12 months compared to the odds of having EQ-5d score = 1 at the baseline visit. Participants completed the EQ-5D questionnaire at baseline and months 3, 6 and 12. General estimating equations with a log link were used to assess the odds ratio at 12 months.

Outcome measures

Measure	Adalimumab (ADA) n=113 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
EQ-5D (Health Utility)	0.89 Odds ratio Interval 0.6 to 1.32	1.17 Odds ratio Interval 0.78 to 1.74

SECONDARY outcome

Timeframe: 12 months

Standard Form 36 item (SF-36) questionnaire is a validated participant reported measure of health related-quality of life.

The physical component summary (PCS) is a score derived from the SF-36 that reflects a person's physical well-being.

Range of scores is 0 to 100. Higher scores indicated better physical health. The minimally important clinical difference is 3-5 points.

Outcome measure is the change in physical health score from baseline to 12 months. Participants completed the questionnaire at baseline and months 3, 6, and 12. The mean change from baseline at 12 months was estimated with a mixed model.

Outcome measures

Measure	Adalimumab (ADA) n=113 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
General Health-related Quality of Life -Physical Component (SF-36)	-0.29 Difference in score on a scale Interval -2.01 to 1.42	-1.68 Difference in score on a scale Interval -3.27 to -0.08

SECONDARY outcome

Timeframe: 12 months

Standard Form 36 item (SF-36) questionnaire is a validated participant reported measure of health related-quality of life.

The mental health component summary (MCS) is a score derived from the SF-36 that reflects a person's mental health and well-being. Range of scores is 0 to 100. Higher scores indicate better mental health. The minimally important clinical difference is 3-5 points. Outcome measure is the change in mental health score from baseline to 12 months. Participants completed the questionnaire at baseline and months 3, 6, and 12. The change from baseline at 12 months was estimated with a mixed model.

Outcome measures

Measure	Adalimumab (ADA) n=113 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Quality of Life Mental Health Component Standard Form 36 Item (SF-36)	1.56 Difference in score on a scale Interval -0.55 to 3.67	0.97 Difference in score on a scale Interval -1.19 to 3.13

SECONDARY outcome

Timeframe: 12 months

Vision-related quality of life was measured by the vision targeted subscale (excluding general health) from the National Eye Institute Visual Functioning Questionnaire 25 item (VFQ-25). The VFQ-25 is a validated, participant reported measure of the aspects of visual functioning that are most important for persons who have chronic eye diseases. Higher scores indicate better vision. Scores range from 0 to 100. Meaningful difference is 4-6 points. Participants completed the VFQ-25 at baseline and months 3, 6 and 12. The outcome is the change in VFQ-25 from baseline to 12 months estimated with a mixed model.

Outcome measures

Measure	Adalimumab (ADA) n=113 Participants Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 Participants Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Vision-related Quality of Life	6.7 Difference in score on a scale Interval 4.7 to 8.7	5.1 Difference in score on a scale Interval 2.9 to 7.3

SECONDARY outcome

Timeframe: 12 months

Population: Participants with phakic (no prior cataract surgery at baseline) eyes and follow up information

Cumulative percent of uveitis eyes having cataract surgery by 12 months. Whether the patient had cataract surgery in the prior time period was determined at baseline and months 1,2,3,4,5,6,8,10,12 and the cumulative percent of eyes having cataract surgery by12 months was estimated by Kaplan-Meier methods.

Outcome measures

Measure	Adalimumab (ADA) n=176 Eyes with uveitis Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=172 Eyes with uveitis Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Cataract Surgery at 12 Months	2 Cumulative percent of eyes Interval 0.0 to 5.0	11 Cumulative percent of eyes Interval 4.0 to 17.0

Adverse Events

Adalimumab (ADA)

Serious events: 16 serious events

Other events: 108 other events

Deaths: 0 deaths

Conventional Immunosuppression (CON)

Serious events: 13 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Measure	Adalimumab (ADA) n=113 participants at risk Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 participants at risk Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Cardiac disorders Atrial fibrillation	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Cardiac disorders Cardiovascular disorder	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	1.8% 2/110 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Cardiac disorders Myocardial infarction	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Eye disorders Cataract	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Eye disorders Iris bombe	0.88% 1/113 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Eye disorders retinal detachment	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Eye disorders Uveitis glaucoma	1.8% 2/113 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Eye disorders Visual acuity reduced	3.5% 4/113 • Number of events 4 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Abdominal pain	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Enteritis	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	1.8% 2/110 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Inflammatory bowel disease	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Hepatobiliary disorders Cholecystitis	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Infections and infestations Appendicitis	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Infections and infestations Cellulitis	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Infections and infestations Pneumonia	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	1.8% 2/110 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Metabolism and nutrition disorders Hyperkalemia	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ocular lymphoma	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Renal and urinary disorders Nephrolithiasis	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Pregnancy, puerperium and perinatal conditions Miscarriage	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Social circumstances Miscarriage of partner	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.00% 0/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Investigations Intraocular pressure increased	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	1.8% 2/110 • Number of events 2 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Eye disorders Vitreous hemorrahage	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Injury, poisoning and procedural complications Post cataract surgery vision loss	0.88% 1/113 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	0.91% 1/110 • Number of events 1 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.

Other adverse events

Measure	Adalimumab (ADA) n=113 participants at risk Adalimumab administered by subcutaneous injection at dosage and frequency specified below; total duration of treatment is 12 months. Adults (≥ 18 years of age) and adolescents ≥30 kg: 80 mg as initial dose; one week later by 40 mg then 40 mg every two weeks. Adolescents \<30 kg: 40 mg as initial dose; one week later 20 mg then 20 mg every 2 weeks. Adalimumab (ADA): Adalimumab is a fully-human monoclonal antibody to TNF-α, which is approved by the U.S. FDA for the treatment of non-infectious intermediate, posterior, and panuveitides in adults and children 2 years of age and older.	Conventional Immunosuppression (CON) n=110 participants at risk Conventional immunosuppressive agent selected by study ophthalmologist at dose and frequency specified below;12 month treatment duration. Azathioprine: initially 2 mg/kg/day; max dose 200 mg/day. Methotrexate initially 15mg/wk; max dose 25 mg/wk. Mycophenolate initially 1 gm BID; max dose1.5 gm BID. Cyclosporine (Sandimmune - dose 2.5 mg/kg BID and Neoral dose 2 mg/kg BID. Tacrolimus initially 1 mg BID; max dose 3 mg BID. Conventional immunosuppression (CON): The study ophthalmologist will select amongst the permissible drugs (methotrexate, mycophenolate mofetil or azathioprine for antimetabolites; cyclosporine or tacrolimus for calcineurin inhibitors) taking into account the side effect profile of each drug with respect to subject's clinical situation.
Eye disorders Epiretinal membrane	15.0% 17/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	18.2% 20/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Abdominal pain	40.7% 46/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	43.6% 48/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders mouth ulcer	18.6% 21/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	20.9% 23/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Diahrrhea	37.2% 42/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	41.8% 46/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Gingival swelling	20.4% 23/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	21.8% 24/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Nausea	37.2% 42/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	47.3% 52/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Vomiting	13.3% 15/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	16.4% 18/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
General disorders Fatigue	67.3% 76/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	79.1% 87/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
General disorders Impaired healing	24.8% 28/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	40.0% 44/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Infections and infestations Covid-19 infection	9.7% 11/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	15.5% 17/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Infections and infestations Upper respiratory infection	7.1% 8/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	1.8% 2/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Metabolism and nutrition disorders Appetite disorder	33.6% 38/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	41.8% 46/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Metabolism and nutrition disorders Fat redistribution	26.5% 30/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	27.3% 30/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Metabolism and nutrition disorders Fluid retension	40.7% 46/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	46.4% 51/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Musculoskeletal and connective tissue disorders Muscular weekness	38.9% 44/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	48.2% 53/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Musculoskeletal and connective tissue disorders Myalgia	68.1% 77/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	76.4% 84/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Nervous system disorders Dizziness	5.3% 6/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	4.5% 5/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Nervous system disorders Headache	67.3% 76/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	70.9% 78/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Nervous system disorders Tremor	38.1% 43/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	54.5% 60/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Psychiatric disorders Depression/anxiety	53.1% 60/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	60.9% 67/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Psychiatric disorders Insomnia	68.1% 77/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	71.8% 79/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Skin and subcutaneous tissue disorders Easy bruising	48.7% 55/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	53.6% 59/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Skin and subcutaneous tissue disorders Acne	28.3% 32/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	32.7% 36/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Skin and subcutaneous tissue disorders Alopecia	33.6% 38/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	47.3% 52/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Skin and subcutaneous tissue disorders Hair growth abnormal	18.6% 21/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	20.9% 23/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Skin and subcutaneous tissue disorders Rash	30.1% 34/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	29.1% 32/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Skin and subcutaneous tissue disorders Swelling face	45.1% 51/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	60.9% 67/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.
Gastrointestinal disorders Gastric reflux disease	46.0% 52/113 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.	58.2% 64/110 • From enrollment through the 12 months visit (end of treatment) non-serious events were reported on the monthly or bimonthly case report form. Non serious events were analyzed by counting persons who ever reported the event over the 12 month study. Serious adverse events were reported by the clinical site as the event occurred or the site became aware of the event. Adverse event information was available only for participants (ADA N = 113, CID N= 110) who continued in the study past enrollment. Non serious adverse events were collected in both systemic and non-systemic forms. The events were collected systematically (check off list) by asking participants if they experienced any occurrence of a specific diagnosis, event, or side effect symptom on the case report form at each clinic visit. Non-systemic data was collected by asking if the patient experienced any other event or diagnosis. Serious adverse event collection was non systematic via an expediated serious adverse event form.

Additional Information

Elizabeth E. Sugar

JHSPH Center for Clinical Trials

Phone: 410-614-7837

Email: esugar2@jhu.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place