Trial Outcomes & Findings for A Double Blind Study in Pediatric Subjects With Chronic Plaque Psoriasis, Studying Adalimumab vs. Methotrexate (NCT NCT01251614)

NCT ID: NCT01251614

Last Updated: 2017-09-25

Results Overview

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in PASI score at Week 16.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 114 participants
• Primary outcome timeframe: Baseline and Week 16
• Results posted on: 2017-09-25

Participant Flow

Participants were enrolled at 38 sites in Belgium, Canada, Chile, Czech Republic, Germany, Hungary, Italy, Mexico, Netherlands, Poland, Spain, Switzerland, and Turkey.

Participants were randomized to receive adalimumab 0.8 mg/kg, adalimumab 0.4 mg/kg, or methotrexate (MTX) in a 1:1:1 ratio and were stratified according to prior history of etanercept treatment.

Participant milestones

Measure	Methotrexate Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Participants who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.	Adalimumab 0.4 mg/kg In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.	Adalimumab 0.8 mg/kg In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.
Overall Study STARTED	37	39	38
Overall Study Entered Period B	13	18	23
Overall Study Entered Period C	8	11	19
Overall Study Entered Period D	36	36	36
Overall Study COMPLETED	34	26	30
Overall Study NOT COMPLETED	3	13	8

Reasons for withdrawal

Measure	Methotrexate Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Participants who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.	Adalimumab 0.4 mg/kg In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.	Adalimumab 0.8 mg/kg In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.
Overall Study Adverse Event	1	0	1
Overall Study Lack of Efficacy	1	9	4
Overall Study Clearing of Psoriatic Lesions	1	0	0
Overall Study Pregnancy	0	0	2
Overall Study Loss of Disease Control	0	1	0
Overall Study Withdrawal by Subject	0	2	1
Overall Study Lost to Follow-up	0	1	0

Baseline Characteristics

A Double Blind Study in Pediatric Subjects With Chronic Plaque Psoriasis, Studying Adalimumab vs. Methotrexate

Baseline characteristics by cohort

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Participants who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.	Total n=114 Participants Total of all reporting groups
Age, Continuous	13.4 years STANDARD_DEVIATION 3.49 • n=5 Participants	12.6 years STANDARD_DEVIATION 4.43 • n=7 Participants	13.0 years STANDARD_DEVIATION 3.29 • n=5 Participants	13.0 years STANDARD_DEVIATION 3.76 • n=4 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	18 Participants n=7 Participants	21 Participants n=5 Participants	65 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	21 Participants n=7 Participants	17 Participants n=5 Participants	49 Participants n=4 Participants
Race/Ethnicity, Customized White	34 Participants n=5 Participants	34 Participants n=7 Participants	35 Participants n=5 Participants	103 Participants n=4 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized American Indian/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race/Ethnicity, Customized Mutli Race	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Psoriasis Area and Severity Index (PASI)	19.2 units on a scale STANDARD_DEVIATION 10.02 • n=5 Participants	16.9 units on a scale STANDARD_DEVIATION 5.76 • n=7 Participants	18.9 units on a scale STANDARD_DEVIATION 10.03 • n=5 Participants	18.3 units on a scale STANDARD_DEVIATION 8.78 • n=4 Participants
Physician's Global Assessment of Psoriasis Cleared	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Physician's Global Assessment of Psoriasis Minimal	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Physician's Global Assessment of Psoriasis Mild	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Physician's Global Assessment of Psoriasis Moderate	19 Participants n=5 Participants	18 Participants n=7 Participants	17 Participants n=5 Participants	54 Participants n=4 Participants
Physician's Global Assessment of Psoriasis Marked	17 Participants n=5 Participants	15 Participants n=7 Participants	17 Participants n=5 Participants	49 Participants n=4 Participants
Physician's Global Assessment of Psoriasis Severe	0 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in PASI score at Week 16.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16	32.4 percentage of participants	43.6 percentage of participants	57.9 percentage of participants

PRIMARY outcome

Timeframe: Week 16

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories:

• 0 (Cleared): No evidence of scaling, erythema, or plaque elevation;
• 1 (Minimal): Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation;
• 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation;
• 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation;
• 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation;
• 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation.

The percentage of participants achieving a score of clear (0) or minimal (1) is reported.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of "Cleared" (0) or "Minimal" (1) at Week 16	40.5 percentage of participants	41.0 percentage of participants	60.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

A PASI 90 response is at least a 90% reduction (improvement) from Baseline in PASI score at Week 16.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a PASI 90 Response at Week 16	21.6 percentage of participants	30.8 percentage of participants	28.9 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Non-responder imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

A PASI 100 response is a 100% reduction (improvement) from Baseline in PASI score at Week 16.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a PASI 100 Response at Week 16	2.7 percentage of participants	10.3 percentage of participants	18.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: Last observation carried forward (LOCF) imputation was used, the analysis was conducted in the intent-to-treat (ITT) population; only participants with Baseline and at least one post-baseline value are included.

The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

Outcome measures

Measure	Methotrexate n=36 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16	-5.0 units on a scale Standard Deviation 7.11	-4.9 units on a scale Standard Deviation 6.16	-6.6 units on a scale Standard Deviation 6.22

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population; only participants with Baseline and at least one post-baseline value are included.

The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best).

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16	1.9 units on a scale Standard Deviation 10.41	9.5 units on a scale Standard Deviation 12.25	10.8 units on a scale Standard Deviation 15.38

SECONDARY outcome

Timeframe: Period C, Week 16

Population: Non-responder imputation was used, the analysis was conducted in the ITT population who entered Period C.

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over < 5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.

Outcome measures

Measure	Methotrexate n=8 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=11 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=19 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Upon Re-Treatment in Period C	62.5 percentage of participants	27.3 percentage of participants	52.6 percentage of participants

SECONDARY outcome

Timeframe: Period B (36 weeks) and Period D (52 weeks)

Population: This analysis was conducted in the ITT population who entered period B, no imputation was used.

Loss of disease control was defined as a worsening of PGA scores in comparison to Week 16 of Period A by at least 2 grades after treatment withdrawal. The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. Scores range from 0 (no evidence of scaling, erythema, or plaque elevation) to 5 (very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation).

Participants who did not lose disease control in period B continued off drug into period D and were observed off-drug until they finally lost disease control or until the end of the 52 weeks of period D.

Outcome measures

Measure	Methotrexate n=13 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=18 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=23 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Time to Loss of Disease Control for Participants Who Entered Period B	184 days Interval 84.0 to 335.0	217 days Interval 56.0 to 551.0	118 days Interval 79.0 to 194.0

SECONDARY outcome

Timeframe: Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period D, Week 16	77.8 percentage of participants	38.9 percentage of participants	50.0 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period A, Week 4	8.1 percentage of participants	20.5 percentage of participants	28.9 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period A, Week 8	8.1 percentage of participants	35.9 percentage of participants	44.7 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period A, Week 11	18.9 percentage of participants	30.8 percentage of participants	47.4 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period C, Week 0	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period C, Week 16	62.5 percentage of participants	27.3 percentage of participants	52.6 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period D, Week 0	30.6 percentage of participants	19.4 percentage of participants	38.9 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period D, Week 28	69.4 percentage of participants	50.0 percentage of participants	63.9 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period D, Week 40	69.4 percentage of participants	50.0 percentage of participants	61.1 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time Period D, Week 52	75.0 percentage of participants	50.0 percentage of participants	55.6 percentage of participants

SECONDARY outcome

Timeframe: Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; 1 (Minimal): Occasional fine scale over <5% of lesions, faint erythema, minimal plaque elevation; 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation.

The percentage of participants achieving a score of clear (0) is reported.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period D, Week 16	25.0 percentage of participants	11.1 percentage of participants	25.0 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period A, Week 4	0.0 percentage of participants	2.6 percentage of participants	2.6 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period A, Week 8	0.0 percentage of participants	12.8 percentage of participants	5.3 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period A, Week 11	0.0 percentage of participants	10.3 percentage of participants	10.5 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period A, Week 16	8.1 percentage of participants	12.8 percentage of participants	18.4 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period C, Week 0	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period C, Week 16	25.0 percentage of participants	9.1 percentage of participants	15.8 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period D, Week 0	8.3 percentage of participants	5.6 percentage of participants	11.1 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period D, Week 28	33.3 percentage of participants	16.7 percentage of participants	22.2 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period D, Week 40	33.3 percentage of participants	16.7 percentage of participants	27.8 percentage of participants
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time Period D, Week 52	41.7 percentage of participants	25.0 percentage of participants	25.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

A PASI 50 response is at least a 50% reduction (improvement) from Baseline in PASI score.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period A, Week 4	16.2 percentage of participants	41.0 percentage of participants	52.6 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period A, Week 8	40.5 percentage of participants	56.4 percentage of participants	65.8 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period A, Week 11	51.4 percentage of participants	61.5 percentage of participants	71.1 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period A, Week 16	54.1 percentage of participants	66.7 percentage of participants	78.9 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period C, Week 0	62.5 percentage of participants	90.9 percentage of participants	52.6 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period C, Week 16	87.5 percentage of participants	90.9 percentage of participants	89.5 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period D, Week 0	52.8 percentage of participants	63.9 percentage of participants	75.0 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period D, Week 16	91.7 percentage of participants	69.4 percentage of participants	88.9 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period D, Week 28	88.9 percentage of participants	72.2 percentage of participants	86.1 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period D, Week 40	91.7 percentage of participants	63.9 percentage of participants	83.3 percentage of participants
Percentage of Participants Who Achieved a PASI 50 Response Over Time Period D, Week 52	91.7 percentage of participants	66.7 percentage of participants	77.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

A PASI 75 response is at least a 75% reduction (improvement) from Baseline in PASI score.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period A, Week 4	0.0 percentage of participants	15.4 percentage of participants	23.7 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period A, Week 8	13.5 percentage of participants	38.5 percentage of participants	47.4 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period A, Week 11	21.6 percentage of participants	43.6 percentage of participants	60.5 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period C, Week 0	37.5 percentage of participants	18.2 percentage of participants	21.1 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period C, Week 16	75.0 percentage of participants	54.5 percentage of participants	78.9 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period D, Week 0	30.6 percentage of participants	27.8 percentage of participants	50.0 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period D, Week 16	86.1 percentage of participants	50.0 percentage of participants	61.1 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period D, Week 28	80.6 percentage of participants	58.3 percentage of participants	77.8 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period D, Week 40	77.8 percentage of participants	52.8 percentage of participants	75.0 percentage of participants
Percentage of Participants Who Achieved a PASI 75 Response Over Time Period D, Week 52	86.1 percentage of participants	47.2 percentage of participants	72.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

A PASI 90 response is at least a 90% reduction (improvement) from Baseline in PASI score.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period A, Week 4	0.0 percentage of participants	5.1 percentage of participants	5.3 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period A, Week 8	2.7 percentage of participants	20.5 percentage of participants	23.7 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period A, Week 11	2.7 percentage of participants	28.2 percentage of participants	28.9 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period C, Week 0	0.0 percentage of participants	0.0 percentage of participants	10.5 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period C, Week 16	62.5 percentage of participants	27.3 percentage of participants	57.9 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period D, Week 0	25.0 percentage of participants	16.7 percentage of participants	36.1 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period D, Week 16	63.9 percentage of participants	36.1 percentage of participants	38.9 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period D, Week 28	55.6 percentage of participants	33.3 percentage of participants	41.7 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period D, Week 40	55.6 percentage of participants	36.1 percentage of participants	47.2 percentage of participants
Percentage of Participants Who Achieved a PASI 90 Response Over Time Period D, Week 52	66.7 percentage of participants	33.3 percentage of participants	44.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: Non-responder imputation was used, the analysis was conducted in the ITT population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

A PASI 100 response is a 100% reduction (improvement) from Baseline in PASI score.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period A, Week 4	0.0 percentage of participants	0.0 percentage of participants	2.6 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period A, Week 8	0.0 percentage of participants	5.1 percentage of participants	5.3 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period A, Week 11	0.0 percentage of participants	5.1 percentage of participants	10.5 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period C, Week 0	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period C, Week 16	25.0 percentage of participants	9.1 percentage of participants	15.8 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period D, Week 0	8.3 percentage of participants	5.6 percentage of participants	11.1 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period D, Week 16	13.9 percentage of participants	11.1 percentage of participants	25.0 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period D, Week 28	27.8 percentage of participants	13.9 percentage of participants	19.4 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period D, Week 40	30.6 percentage of participants	13.9 percentage of participants	22.2 percentage of participants
Percentage of Participants Who Achieved a PASI 100 Response Over Time Period D, Week 52	41.7 percentage of participants	25.0 percentage of participants	22.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52

Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population.

PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis).

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percent Change From Baseline in PASI Score Over Time Period A, Week 4	-14.0 percent change Standard Deviation 36.71	-36.9 percent change Standard Deviation 38.62	-48.3 percent change Standard Deviation 33.96
Percent Change From Baseline in PASI Score Over Time Period A, Week 8	-30.6 percent change Standard Deviation 45.89	-48.8 percent change Standard Deviation 44.74	-60.3 percent change Standard Deviation 35.98
Percent Change From Baseline in PASI Score Over Time Period A, Week 11	-36.6 percent change Standard Deviation 51.69	-51.4 percent change Standard Deviation 50.19	-62.8 percent change Standard Deviation 38.02
Percent Change From Baseline in PASI Score Over Time Period A, Week 16	-42.8 percent change Standard Deviation 54.24	-52.4 percent change Standard Deviation 51.79	-65.6 percent change Standard Deviation 39.44
Percent Change From Baseline in PASI Score Over Time Period C, Week 0	-59.0 percent change Standard Deviation 20.61	-65.3 percent change Standard Deviation 12.16	-45.8 percent change Standard Deviation 39.64
Percent Change From Baseline in PASI Score Over Time Period C, Week 16	-87.1 percent change Standard Deviation 16.47	-74.5 percent change Standard Deviation 17.79	-69.3 percent change Standard Deviation 69.79
Percent Change From Baseline in PASI Score Over Time Period D, Week 0	-41.8 percent change Standard Deviation 54.99	-46.8 percent change Standard Deviation 49.27	-61.5 percent change Standard Deviation 42.96
Percent Change From Baseline in PASI Score Over Time Period D, Week 16	-82.3 percent change Standard Deviation 31.38	-66.9 percent change Standard Deviation 33.51	-74.5 percent change Standard Deviation 37.44
Percent Change From Baseline in PASI Score Over Time Period D, Week 28	-81.0 percent change Standard Deviation 35.86	-65.8 percent change Standard Deviation 36.99	-81.5 percent change Standard Deviation 22.06
Percent Change From Baseline in PASI Score Over Time Period D, Week 40	-83.0 percent change Standard Deviation 31.94	-64.6 percent change Standard Deviation 37.46	-82.1 percent change Standard Deviation 23.99
Percent Change From Baseline in PASI Score Over Time Period D, Week 52	-86.3 percent change Standard Deviation 28.92	-58.7 percent change Standard Deviation 53.21	-80.1 percent change Standard Deviation 24.17

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52

Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population with available data at baseline.

The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

Outcome measures

Measure	Methotrexate n=36 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Change From Baseline in CDLQI Over Time Period A, Week 4	-2.9 units on a scale Standard Deviation 5.24	-3.9 units on a scale Standard Deviation 5.22	-4.9 units on a scale Standard Deviation 5.80
Change From Baseline in CDLQI Over Time Period A, Week 8	-4.0 units on a scale Standard Deviation 6.44	-4.1 units on a scale Standard Deviation 6.29	-5.5 units on a scale Standard Deviation 5.66
Change From Baseline in CDLQI Over Time Period C, Week 0	-6.1 units on a scale Standard Deviation 4.55	-4.7 units on a scale Standard Deviation 9.08	-6.1 units on a scale Standard Deviation 6.92
Change From Baseline in CDLQI Over Time Period C, Week 4	-9.8 units on a scale Standard Deviation 3.92	-5.5 units on a scale Standard Deviation 7.24	-7.0 units on a scale Standard Deviation 6.63
Change From Baseline in CDLQI Over Time Period D, Week 0	-5.6 units on a scale Standard Deviation 7.55	-5.5 units on a scale Standard Deviation 5.95	-6.8 units on a scale Standard Deviation 6.70
Change From Baseline in CDLQI Over Time Period D, Week 11	-8.5 units on a scale Standard Deviation 5.37	-6.8 units on a scale Standard Deviation 7.07	-7.4 units on a scale Standard Deviation 6.21
Change From Baseline in CDLQI Over Time Period D, Week 28	-8.3 units on a scale Standard Deviation 5.93	-6.8 units on a scale Standard Deviation 7.91	-8.4 units on a scale Standard Deviation 6.72
Change From Baseline in CDLQI Over Time Period D, Week 52	-8.4 units on a scale Standard Deviation 6.08	-6.6 units on a scale Standard Deviation 8.12	-8.2 units on a scale Standard Deviation 6.75

SECONDARY outcome

Timeframe: Period A, Weeks 4, 8 and 16, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52

Population: Non-responder imputation was used, the analysis was conducted in the intent to-treat (ITT) population.

The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired and a score of 0 indicates no impairment in quality of life.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Percentage of Participants With CDLQI = 0 Over Time Period A, Week 8	10.8 percentage of participants	12.8 percentage of participants	5.3 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period A, Week 4	5.4 percentage of participants	5.1 percentage of participants	10.5 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period A, Week 16	10.8 percentage of participants	20.5 percentage of participants	23.7 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period C, Week 0	0.0 percentage of participants	36.4 percentage of participants	21.1 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period C, Week 4	12.5 percentage of participants	36.4 percentage of participants	31.6 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period D, Week 0	16.7 percentage of participants	22.2 percentage of participants	27.8 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period D, Week 11	25.0 percentage of participants	16.7 percentage of participants	33.3 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period D, Week 28	30.6 percentage of participants	22.2 percentage of participants	30.6 percentage of participants
Percentage of Participants With CDLQI = 0 Over Time Period D, Week 52	41.7 percentage of participants	16.7 percentage of participants	33.3 percentage of participants

SECONDARY outcome

Timeframe: Period A, 16 weeks

Population: Analysis was conducted in the intent to-treat (ITT) population.

Participants who did not have a response during Period A were censored.

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Time to PASI 50/75/90/100 Response in Period A PASI 50	76 days Interval 56.0 to 112.0	55 days Interval 28.0 to 115.0	30 days Interval 28.0 to 77.0
Time to PASI 50/75/90/100 Response in Period A PASI 75	116 days Interval 111.0 to Not estimable due to the low number of events	107 days Interval 56.0 to Not estimable due to the low number of events	59 days Interval 53.0 to Not estimable due to the low number of events
Time to PASI 50/75/90/100 Response in Period A PASI 90	NA days Interval 112.0 to Not estimable due to the low number of events	NA days Interval 78.0 to Not estimable due to the low number of events	NA days Interval 76.0 to Not estimable due to the low number of events
Time to PASI 50/75/90/100 Response in Period A PASI 100	NA days Not estimable due to the low number of events	NA days Not estimable due to the low number of events	NA days Not estimable due to the low number of events

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4 and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52

Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population with available data at baseline.

The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best).

Outcome measures

Measure	Methotrexate n=37 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Change From Baseline in PedsQL Over Time Period A, Week 4	-0.8 units on a scale Standard Deviation 11.75	4.9 units on a scale Standard Deviation 13.80	8.1 units on a scale Standard Deviation 11.95
Change From Baseline in PedsQL Over Time Period A, Week 8	0.5 units on a scale Standard Deviation 10.18	7.0 units on a scale Standard Deviation 13.16	8.8 units on a scale Standard Deviation 15.45
Change From Baseline in PedsQL Over Time Period C, Week 0	3.0 units on a scale Standard Deviation 10.45	8.9 units on a scale Standard Deviation 25.35	14.2 units on a scale Standard Deviation 20.25
Change From Baseline in PedsQL Over Time Period C, Week 4	5.2 units on a scale Standard Deviation 11.08	11.6 units on a scale Standard Deviation 25.19	16.3 units on a scale Standard Deviation 17.35
Change From Baseline in PedsQL Over Time Period D, Week 0	2.3 units on a scale Standard Deviation 10.93	9.4 units on a scale Standard Deviation 16.90	10.5 units on a scale Standard Deviation 15.86
Change From Baseline in PedsQL Over Time Period D, Week 11	5.4 units on a scale Standard Deviation 10.36	12.8 units on a scale Standard Deviation 19.03	12.0 units on a scale Standard Deviation 16.13
Change From Baseline in PedsQL Over Time Period D, Week 28	8.0 units on a scale Standard Deviation 13.40	14.5 units on a scale Standard Deviation 20.19	13.1 units on a scale Standard Deviation 16.23
Change From Baseline in PedsQL Over Time Period D, Week 52	8.6 units on a scale Standard Deviation 13.93	14.0 units on a scale Standard Deviation 20.40	13.8 units on a scale Standard Deviation 15.36

SECONDARY outcome

Timeframe: Baseline, Period A, Weeks 4, 8, and 16

Population: LOCF imputation was used, the analysis was conducted in the intent-to-treat (ITT) population with available data at baseline.

The CDI:S is a short 10-item self-rated symptom-oriented scale used to screen for depressive symptoms. CDI:S scores range from 0 to 100, with a lower score indicating fewer depressive symptoms.

Outcome measures

Measure	Methotrexate n=36 Participants Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=35 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=36 Participants In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.
Change From Baseline in the Children's Depression Inventory: Short (CDI:S) Period A, Week 4	0.6 units on a scale Standard Deviation 8.85	-1.0 units on a scale Standard Deviation 6.64	-3.6 units on a scale Standard Deviation 5.86
Change From Baseline in the Children's Depression Inventory: Short (CDI:S) Period A, Week 8	0.2 units on a scale Standard Deviation 5.26	-1.5 units on a scale Standard Deviation 7.52	-1.6 units on a scale Standard Deviation 5.52
Change From Baseline in the Children's Depression Inventory: Short (CDI:S) Period A, Week 16	-2.0 units on a scale Standard Deviation 5.88	-3.3 units on a scale Standard Deviation 8.12	-2.3 units on a scale Standard Deviation 6.29

Adverse Events

Methotrexate

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Adalimumab 0.4 mg/kg

Serious events: 3 serious events

Other events: 27 other events

Deaths: 0 deaths

Adalimumab 0.8 mg/kg

Serious events: 0 serious events

Other events: 23 other events

Deaths: 0 deaths

Period B: MTX/No Treatment

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Period B: ADA 0.4 mg/kg/No Treatment

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Period B: ADA 0.8 mg/kg/No Treatment

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Period C: Adalimumab 0.4 mg/kg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Period C: Adalimumab 0.8 mg/kg

Serious events: 0 serious events

Other events: 16 other events

Deaths: 0 deaths

Period D: Adalimumab 0.4 mg/kg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Period D: Adalimumab 0.8 mg/kg

Serious events: 5 serious events

Other events: 64 other events

Deaths: 0 deaths

Serious adverse events

Measure	Methotrexate n=37 participants at risk Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 participants at risk In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 participants at risk In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Period B: MTX/No Treatment n=13 participants at risk Participants initially randomized to methotrexate who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.	Period B: ADA 0.4 mg/kg/No Treatment n=18 participants at risk Participants initially randomized to adalimumab (ADA) 0.4 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.	Period B: ADA 0.8 mg/kg/No Treatment n=23 participants at risk Participants initially randomized to adalimumab (ADA) 0.8 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.	Period C: Adalimumab 0.4 mg/kg n=11 participants at risk Participants initially randomized to adalimumab 0.4 mg/kg with loss of disease control in Period B received adalimumab 0.4 mg/kg eow for up to 16 weeks in Period C.	Period C: Adalimumab 0.8 mg/kg n=27 participants at risk Participants initially randomized to either methotrexate or adalimumab 0.8 mg/kg with loss of disease control in Period B received adalimumab 0.8 mg/kg eow for up to 16 weeks in Period C.	Period D: Adalimumab 0.4 mg/kg n=13 participants at risk Participants received adalimumab 0.4 mg/kg eow for up to 52 weeks in Period D.	Period D: Adalimumab 0.8 mg/kg n=87 participants at risk Participants received adalimumab 0.8 mg/kg eow for up to 52 weeks in Period D.
General disorders Chest Pain	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Gastrointestinal Infection	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Fall	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Tendon Injury	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Eye Naevus	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Psychiatric disorders Agitation	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Reproductive system and breast disorders Haemorrhagic Ovarian Cyst	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Rash Maculo-Papular	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.

Other adverse events

Measure	Methotrexate n=37 participants at risk Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1.	Adalimumab 0.4 mg/kg n=39 participants at risk In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Adalimumab 0.8 mg/kg n=38 participants at risk In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets.	Period B: MTX/No Treatment n=13 participants at risk Participants initially randomized to methotrexate who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.	Period B: ADA 0.4 mg/kg/No Treatment n=18 participants at risk Participants initially randomized to adalimumab (ADA) 0.4 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.	Period B: ADA 0.8 mg/kg/No Treatment n=23 participants at risk Participants initially randomized to adalimumab (ADA) 0.8 mg/kg who responded in Period A were withdrawn from active therapy in Period B for up to 36 weeks.	Period C: Adalimumab 0.4 mg/kg n=11 participants at risk Participants initially randomized to adalimumab 0.4 mg/kg with loss of disease control in Period B received adalimumab 0.4 mg/kg eow for up to 16 weeks in Period C.	Period C: Adalimumab 0.8 mg/kg n=27 participants at risk Participants initially randomized to either methotrexate or adalimumab 0.8 mg/kg with loss of disease control in Period B received adalimumab 0.8 mg/kg eow for up to 16 weeks in Period C.	Period D: Adalimumab 0.4 mg/kg n=13 participants at risk Participants received adalimumab 0.4 mg/kg eow for up to 52 weeks in Period D.	Period D: Adalimumab 0.8 mg/kg n=87 participants at risk Participants received adalimumab 0.8 mg/kg eow for up to 52 weeks in Period D.
Gastrointestinal disorders Abdominal Pain	10.8% 4/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.1% 2/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	6.9% 6/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	6.9% 6/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Gastrointestinal disorders Dyspepsia	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.1% 2/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Gastrointestinal disorders Nausea	10.8% 4/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 3/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.3% 2/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.4% 2/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.5% 10/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Gastrointestinal disorders Vomiting	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 3/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.6% 1/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.4% 2/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.4% 3/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
General disorders Asthenia	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.1% 2/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
General disorders Chest Pain	5.4% 2/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
General disorders Fatigue	5.4% 2/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	10.3% 4/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.4% 2/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
General disorders Injection Site Pain	8.1% 3/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.9% 3/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
General disorders Injection Site Reaction	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.3% 2/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
General disorders Pyrexia	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 3/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.6% 1/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Bronchitis	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.7% 5/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Gastroenteritis	8.1% 3/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.3% 2/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	9.1% 1/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Influenza	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	10.3% 9/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Lice Infestation	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Nasopharyngitis	18.9% 7/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	25.6% 10/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	21.1% 8/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.6% 1/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	17.4% 4/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	9.1% 1/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	18.5% 5/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	23.1% 3/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	28.7% 25/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Oral Herpes	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.4% 2/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.3% 2/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Pharyngitis	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	6.9% 6/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Pharyngitis Streptococcal	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Rhinitis	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.9% 3/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.4% 3/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Upper Respiratory Tract Infection	16.2% 6/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	10.3% 4/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.3% 2/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.1% 2/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.1% 3/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	14.9% 13/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Urinary Tract Infection	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Varicella	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Infections and infestations Viral Upper Respiratory Tract Infection	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.4% 2/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.3% 2/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Contusion	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.6% 1/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.4% 3/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Joint Injury	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Laceration	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Injury, poisoning and procedural complications Thermal Burn	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Metabolism and nutrition disorders Decreased Appetite	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	9.1% 1/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Musculoskeletal and connective tissue disorders Arthralgia	5.4% 2/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.4% 3/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.3% 2/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.1% 3/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Musculoskeletal and connective tissue disorders Joint Effusion	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.6% 1/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Skin Papilloma	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.4% 2/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Nervous system disorders Headache	10.8% 4/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	17.9% 7/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	15.8% 6/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.1% 2/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.1% 3/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	25.3% 22/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Psychiatric disorders Agitation	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Psychiatric disorders Insomnia	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	9.1% 1/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Respiratory, thoracic and mediastinal disorders Asthma	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Respiratory, thoracic and mediastinal disorders Cough	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	10.3% 4/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	11.1% 2/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	18.2% 2/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.4% 3/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	5.4% 2/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.3% 2/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	6.9% 6/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.6% 1/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Dry Skin	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.9% 3/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	5.1% 2/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Eczema Vesicular	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Pruritus	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 3/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	9.1% 1/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	3.7% 1/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.6% 4/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Pruritus Generalised	0.00% 0/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	9.1% 1/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	1.1% 1/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.
Skin and subcutaneous tissue disorders Psoriasis	2.7% 1/37 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/39 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	2.6% 1/38 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/18 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	4.3% 1/23 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/11 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	0.00% 0/27 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	7.7% 1/13 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.	6.9% 6/87 • Period A - up to 16 weeks; Period B - up to 36 weeks; Period C - up to 16 weeks; Period D - up to 52 weeks.

Additional Information

Global Medical Services

AbbVie (prior sponsor Abbott)

Phone: 800-633-9110

Results disclosure agreements

• Principal investigator is a sponsor employee AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
• Publication restrictions are in place

Restriction type: OTHER