Trial Outcomes & Findings for Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis (NCT NCT01704599)

NCT ID: NCT01704599

Last Updated: 2015-02-04

Results Overview

PASI: formula based on body surface areas on head/neck, trunk, both arms \& legs with disease quality grading induration, scale and erythema on participants ages 18-65 with moderate to severe plaque psoriasis measured at weeks 16 and 28.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 8 participants
• Primary outcome timeframe: Weeks 16 and 28
• Results posted on: 2015-02-04

Participant Flow

All subjects were recruited at one of the Two Wayne State University Physician Group Dermatology clinics . Recruitment began Oct 2010 and lasted until 2012

There were 11 potential subjects analyzed of which 3 were not enrolled prior to study assignment. The 3 did not meet study criteria.

Participant milestones

Measure	Humira Then Humira Plus 3 B Vitamins Humira then Humira plus 3 B vitamins The one arm: After 16 weeks on adalimumab, modulators of homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) will be added to adalimumab therapy for an additional 12 weeks. At end of this, therapy can stop or continue . Telephone call day 70 after formal end of in person study the investigators will assess general health of each subject. Humira Then Humira plus 3 B vitamins: Humira alone for 16 weeks then Humira plus 100 mg daily pyridoxine, 5 mg daily folic acid and 1000 mcg daily cyanocobalamin
Overall Study STARTED	8
Overall Study COMPLETED	7
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure

Humira Then Humira Plus 3 B Vitamins Humira then Humira plus 3 B vitamins The one arm: After 16 weeks on adalimumab, modulators of homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) will be added to adalimumab therapy for an additional 12 weeks. At end of this, therapy can stop or continue . Telephone call day 70 after formal end of in person study the investigators will assess general health of each subject. Humira Then Humira plus 3 B vitamins: Humira alone for 16 weeks then Humira plus 100 mg daily pyridoxine, 5 mg daily folic acid and 1000 mcg daily cyanocobalamin

Overall Study Adverse Event

1

Baseline Characteristics

Addition of Modulators of Homocysteine to Adalimumab Therapy in the Treatment of Moderate to Severe Plaque Psoriasis

Baseline characteristics by cohort

Measure	Humira Then Humira Plus 3 B Vitamins n=8 Participants Humira then Humira plus 3 B vitamins The only arm: After 16 weeks on adalimumab, modulators of homocysteine (oral vitamin B12, oral vitamin B6 or pyridoxine, and oral folic acid) will be added to adalimumab therapy for an additional 12 weeks. At end of this therapy can stop or continue . Telephone call day 70 after formal end of in person study the investigators will assess general health of each subject. Humira Then Humira plus 3 B vitamins: Humira alone for 16 weeks then Humira plus 100 mg daily pyridoxine, 5 mg daily folic acid and 1000 mcg daily cyanocobalamin
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
number enrolled participants	8 participants 8 n=5 Participants
Adult patients with plaque psoriasis >10% BSA Male	5 participants n=5 Participants
Adult patients with plaque psoriasis >10% BSA Female	3 participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 16 and 28

Population: 8 adults ages 18-65 with moderate to severe plaque psoriasis. Seven of 8 had PASI measured at weeks 16 and 28. One had SAE prior to week 16.

PASI: formula based on body surface areas on head/neck, trunk, both arms & legs with disease quality grading induration, scale and erythema on participants ages 18-65 with moderate to severe plaque psoriasis measured at weeks 16 and 28.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change Improved	4 participants
Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change Unchanged	1 participants
Number of Particpants With a Categorical PASI (Psoriasis Area and Severity Index) Change Worsened	2 participants

SECONDARY outcome

Timeframe: Week 16 and Week 28

Population: 8 adult participants with moderate to severe plaque psoriasis. 7 had static PGA scores weeks 16 and 28 and one had sPGA but SAE prior to week 16.

Number of participants with a category change in Physician static Global Assessment (sPGA): 7 point score from 0 (clear) to 6 measuring amount of surface covered and plaque qualities: thickness & erythema plus scaling. Dynamic score compares baseline with either improvement/ worsening of the same factors measured in the sPGA using the 0-6 scoring range but focused on change. sPGA at weeks 16 AND 28. dynamic PGA to be categoically measured at.weeks16 and 28.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA): Unchanged	1 participants
Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA): Worsened	3 participants
Number of Participants With a Categorical Change in Static Physician Global Assessment (sPGA): Improved	3 participants

SECONDARY outcome

Timeframe: Week 16 and Week 28

Population: 8 adults with moderate to severe plaque psoriasis measured at weeks 16 and 28. Seven were measured weeks 16 and 28. One had SAE prior to week 16.

DLQI is 10 questions examining impact of skin disease on quality of life: (1) symptoms & feelings (2) daily activities (3) leisure (4) work & school (5) personal relationship (6) treatment. To be administered to adults over 18 years with moderate to severe plaque psoriasis at week 0 (no systemic psoriasis medication);. weeks 16 ( after 16 weeks of adalimumab) and week 28 (after 16 weeks adalimumab then 12 weeks of adalimumab plus daily 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12).

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change Improved	3 participants
Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change Unchanged	3 participants
Number of Participants With a Categorical DLQI (Dermatology Life Quality Index) Change Worsened	1 participants

SECONDARY outcome

Timeframe: At Screening visit, Week 16 on Humira, after another 12 weeks on Humira plus vitamins and if early termination

Population: 8 adult subjects age 18-65 with moderate to sefver plaque psoriasis. Five subjects had VEGF levels taken weeks 16 and 28. Three ( one wiht SAE prior to week 16) did not.

Adult particpants ages 18 or older with moderate to severe plaque psoriasis were to have serum VEGF measured at week 0 on no systemic psoriasis medication then at both weeks 16 on adalimumab and at week 28 on adalimumab plus folic acid, B6 and Vitamin B12. Subjects raniked by BMI week 0 low to high

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants With Category Change in Serum VEGF (Vascular Endothelial Growth Factorl) Increased	4 participants
Number of Participants With Category Change in Serum VEGF (Vascular Endothelial Growth Factorl) Unchanged	0 participants
Number of Participants With Category Change in Serum VEGF (Vascular Endothelial Growth Factorl) Decreased	1 participants

SECONDARY outcome

Timeframe: Week 16 and Week 28

Population: 8 adults 18-65 with moderate to severe plaque psoriasis. 4 had levels measured at Week 16 and again at Week 28. Of the 4 not meausres 1 had a SAE prior to Week16.

Serum homocysteine measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumaband then 12 weeks of adalimumab plus 5 mg folic acid, 100mg B6 and 1000 mcg of B12 in adults ages 18-65 with moderate to sever plaque psoriasis..

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=4 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine Increased	1 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine Unchanged	0 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Homocysteine Decreased	3 participants

SECONDARY outcome

Timeframe: At Week 16 and Week 28

Population: 8 adult participants ages 18-65 with moderate to severe plaque psoriasis. Five of 8 had B12 measured at weeks 16 and 28. Three did not. One of the 3 had SAE prior to week 16.

Adult participants 18 years or older with moderate to severe plaque psoriasis were to have serum B12 levels measures Weeks 0 (on no systemic psoriasis medication), 16 (on adalimumab) and week 28 (on adalimumab plus daily 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants With Category Change in Vitamin B12 Blood Level Increased	5 participants
Number of Participants With Category Change in Vitamin B12 Blood Level Unchanged	0 participants
Number of Participants With Category Change in Vitamin B12 Blood Level Worsened	0 participants

SECONDARY outcome

Timeframe: At Week 16 and Week 28

Population: 8 adults 18-65 with moderate to severe plaque psoriasis measured at weeks 16 and 28. .Four of 8 had levels drawn at weeks 16 and 28. Four did not. Of the four whoi did not one had a SAE prior to Week 16.

Serum vitamin B6 levels were to be measured weeks16 after 16 weeks adalimumab and at week 28 after 16 weeks adalimumab and 12 weeks on adalimuamb, folic acid 5 mg, b6 100 mg and B12 1000 mcg in adult participants with moderate to sever plque psoriasis.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=4 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Increasing and Decreasing Serum Vitamin B6 Level Increased	4 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Vitamin B6 Level Unchanged	0 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Vitamin B6 Level Decreased	0 participants

SECONDARY outcome

Timeframe: Weeks 16 and 28

Population: 8 particpantts with psoriasis. Five had folic acid levels drawn weeks 16 and 28. Three did not (one of the 3 had a SAE prior to week 16).

Serum folic acid level in adults ages 18 and older with mild to moderate plaque psoriasis measured at week 16 after 16 weeks adalimumab and at week 28 after 16 weeks adalimumab plus 12 weeks of adalimumab and daily 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants With Category Change in Serum Folic Acid Level. Increased	3 participants
Number of Participants With Category Change in Serum Folic Acid Level. Unchanged	0 participants
Number of Participants With Category Change in Serum Folic Acid Level. Decreased	0 participants
Number of Participants With Category Change in Serum Folic Acid Level. Not evaluable (if >20 ng/ml only stated as such)	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: After Week 16 of study

Population: 8 adult participants ages 18-65 with moderate to severe plaque psoriasis. Seven assessed after week 16 and at Week 28 of study and assessed at day 70 post week 28 visit ( the latter by telephone). One subject had SAE prior to vitamin addition.

Worsening psoriasis or development or worsening of measured condition or new pathology not seen by week 16 but developed at weeks 28 or first discoved by telephone call day 70 post study:

AE Humira only

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants in the Categories of Having and Not Having an Adverse Event No Adverse Event after Week 16	2 participants
Number of Participants in the Categories of Having and Not Having an Adverse Event Adverse Event Weeks 16-28	4 participants
Number of Participants in the Categories of Having and Not Having an Adverse Event Adverse event by Day 70 call after Week 28	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: By Week 16, by Week 28 and by Day 70 post Week 28.

Population: Adults ages 18-65 with moderate to severe plaque psoriasis.

A serious adverse event is hosptalization or death or pathology leading to early termination of a participant from the study. This was to be reported at anytime during the 28 week study of adult patients ages 18-65 with moderate to severe plaque psoriasis though categorized by Week 16 (on adalimumab alone, by Week 28 (on adalimuamb plus 3 B vitaminsand by day 70 post Week 28.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=8 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants in the Categories of Having and of Not Having a Serious Adverse Event (SAE) SAE by Week 16	1 participants
Number of Participants in the Categories of Having and of Not Having a Serious Adverse Event (SAE) SAE by Week 28	0 participants
Number of Participants in the Categories of Having and of Not Having a Serious Adverse Event (SAE) SAE by Day 70 afterWeek 28	0 participants
Number of Participants in the Categories of Having and of Not Having a Serious Adverse Event (SAE) No SAE	7 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 16 and then Week 28 after another 12 weeks on Humira plus vitamins and if early termination

Population: 8 adults with moderate to severe plaque psoriasis. Seven evaluated at weeks 0,16 and 28 for no change in electrocardiogram (EKG) , worsening arrhymia or improvement of arrhythmia at weeks 16 and 28. Five of 8 studied weeks 0,16 and 28; 1 at week 16 and 28. Two (one with the SAE prior to Week 16) did not have EKGs both at weeks 16 and 28.

An electrocardiogram (EKG) is used to evaluate the electrical activity of the heart by converting this activity into line tracings on paper.. Electrodes (small, plastic patches) are placed at certain locations on the chest, arms, and legs. When the electrodes are connected to an EKG machine by lead wires, the electrical activity of the heart is measured, interpreted, and printed out for the doctor's information and further interpretation. This test was to be administered to adults age 18 or older with moderate to severe plaque psoriasis patients at week 0, 16 and week 28 of this study.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=6 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants in the Categories of Normalizing, Unchanging and Newly Abnormal Electrocardiograms (EKGs) Normalizing	1 participants
Number of Participants in the Categories of Normalizing, Unchanging and Newly Abnormal Electrocardiograms (EKGs) Unchanged	4 participants
Number of Participants in the Categories of Normalizing, Unchanging and Newly Abnormal Electrocardiograms (EKGs) Newly abnormal	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 16 and Week 28

Population: 8 adult participants with moderate to severe plaque psoriasis. Five had CBCs at both week 16 and week 28. three did not ( one of the 3 had a SAE pripor to week 16)

Change in CBC parameter: white blood count or hemoglobin or hematocrit ( as measured week 16 on adalimumab and at week 28 after 12 more weeks on adalimuamb , folic acid, B6 and B12) in adults ages 18-65 with moderate to severe plaque psoriasis.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count) WBC increased	3 participants
Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count) WBC unchanged	0 participants
Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count) WBC decreased	2 participants
Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count) Hemoglobin/Hematocrit increased	3 participants
Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count) Hemoglobin/Hematocrit unchanged	0 participants
Number of Participants in Categories or Increasing and Decreasing Changes Within the CBC (Complete Blood Count) Hemoglobin/Hematocrit decreased	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 16 and 28

Population: 8 Adults age 18-65 with moderate to severe plaque psoriasis.Five had results both weeks 16 and 28. Three did npot (of these 1 had SAE prior to week 16)

Serum magnesium (Mg) was to be measured at baseline, Week 16 (on adalimumab) and at week 28 (on adalimumab plus folic acid, vitamins B6 and B12) in adult participants age 18 or older with moderate to severe plaque psoriasis.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Increasing and Decreasing Serum Magnesium Increased	1 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Magnesium Unchanged	2 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Magnesium Decreased	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 16 then Week 28

Population: 8 adults 18-65 years having moderate to severe plaque psoriasis. Five had levels measured at week 16 and and again at week 28 . Three did not . Of the 3 1 had SAE prior to week 16.

Serum phosphorus (P) levels were to be measured weeks16 and 28 in adult participants age 18 and older with moderate to severe plaque psoriasis at week 0 on no systemic psoriasis medication; week 16 after 16 weeks of adalimumab and at week 28 after 16 weeks of adalimumab plus 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Increasing and Decreasing Serum Phosphorus Increased	3 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Phosphorus Unchanged	0 participants
Number of Participants Within the Categories of Increasing and Decreasing Serum Phosphorus Decreased	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 28 after 16 weeks of Adalimumab then 12 of Adalimumab-Vitamins

Population: 8 adult participants with moderate to severe plaque psoriasis with H. pylori titers measured during the 28 week study.

Adult participants age 18 years or older with moderate to severe plaque psoriasis with serum IgG antibodies against Helicobacter pylori bacteria using commercial ELISA assay during the 28 week study.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=8 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Elevated and Normal Helicobacter Pylori Antibody Elevated	2 participants
Number of Participants Within the Categories of Elevated and Normal Helicobacter Pylori Antibody Normal	6 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: At screening

Population: Only 1 of the 8 subjects was a woman of childbearing years during the study.

Women of childbearing years over age 18 with moderate to severe plaque psoriasis on no systemic therapy at week 0 of study.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=1 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Positive Urine Pregnancy Test (Urine Hcg) Negative	1 participant
Number of Participants Within the Categories of Positive Urine Pregnancy Test (Urine Hcg) Positive	0 participant

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 16 and Week 28

Population: of 8 adults with moderate to severe plaque psoriasis, Seven participants were measured at week 16 after 16 weeks adalimumab and at week 28 after 16 weeks adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg B12. One who had SAE prior to Week 16 did not..

Blood pressure is the force the heart exerts against the walls of arteries as it pumps the blood out to the body. The unit of measurement is millimeters of mercury (mm Hg). Pulse is the number of times your heart beats per minute. The unit of measurement is beats per minute (BPM). These test measurements compared in adults with moderate to severe plaque psoriasis week 16 after 16 weeks adalimumab and week 28 after 16 weeks adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg vitamin B12.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Systolic BP increased	4 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Systolic BP decreased	3 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Diastolic BP increased	5 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Systolic BP unchanged	0 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Diastolic BP unchanged	0 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Diastolic BP decreased	2 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Pulse increased	5 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Pulse unchanged	0 participants
Number of Participants Within the Categories of Increasing and Decreasing Blood Pressure and Pulse Measures: Pulse decreased	2 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 16 and 28

Population: 8 Subjects. Five had temperatures measured weeks 16 and 28. Three did not (one of the 3 had SAE prior to week16)

Using a thermometer for body temperature on degrees Fahrenheit. Participants to be measured were adults 18 years or older with moderate to severe plaque psoriasis with temperature to be measured at week 16 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=5 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within Categories of Body Temperature Change increased	2 participants
Number of Participants Within Categories of Body Temperature Change unchanged	2 participants
Number of Participants Within Categories of Body Temperature Change decreased	1 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 0 at Start of Adalimumab

Population: 8 Adults with mild to moderate plaque psoriasis had their height measured at week 0 in inches.

Height is the distance from the bottom (soles of feet ) to the top (top of head) of a person when that person is standing in this study using ruler in inches.Participants measured were adults age 18 or older with moderate to severe plaque psoriasis.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=8 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Who Fulfilled the Category of Having Height Measured Measured	8 participants
Number of Participants Who Fulfilled the Category of Having Height Measured Not measured	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 16 and Week 28

Population: 8 adults ages 18-65 with moderate to severe plaque psoriasis. Seven of 8 had weights taken weeks 0,4,16 and 28 allowing week16 and 28 analysis. One had weight taken only at weeks 0 and 4.

Weight is how heavy a participant is. Weight in pounds of each study adult participant age 18-65 years with moderate to severe plaque psoriasis measured at weeks 16 and compared to week 28 of study.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Number of Participants Within the Categories of Increasign and Decreasing Body Weight Decreased	5 participants
Number of Participants Within the Categories of Increasign and Decreasing Body Weight Increased	2 participants
Number of Participants Within the Categories of Increasign and Decreasing Body Weight Unchanged	0 participants

POST_HOC outcome

Timeframe: Week 16 and Week 28

Population: 8 Adult subjects ages 18-65 with moderate to severe plaque psoriasis. 7 had PASI data both Week 16 and Week 28. The 1 who did not had SAE prior to Week 16.

Change in PASI from Week 16 on adalimumab to Week 28 on adalimumab, folic acid, vitamin B6 and B12 in adults ages 18-65 with moderate to severe plaque psoriasis.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
PASI Change Related to Baseline Body Mass Index Above, Below and Equal to 27.3 BMI >27.3 who improved	4 participants
PASI Change Related to Baseline Body Mass Index Above, Below and Equal to 27.3 BMI<27.3 who worsened	2 participants
PASI Change Related to Baseline Body Mass Index Above, Below and Equal to 27.3 BMI >27.3 who worsened	0 participants
PASI Change Related to Baseline Body Mass Index Above, Below and Equal to 27.3 BMI of 27.3 who were unchanged	0 participants
PASI Change Related to Baseline Body Mass Index Above, Below and Equal to 27.3 BMI<27.3 who improved	0 participants

POST_HOC outcome

Timeframe: Week 16 and Week 28

Population: 8 adult participants with moderate to severe plaque psoriasis ages 18 to 65. Seven were analyzed. The one not analyzed had SAE prior to week16.

Baseline VEGF level at week zero related to PASI change Week 16 on adalimumab compared to Week 28 after additonal 12 weeks of adalimumab plus folic acid, vitamin B6 and B12 in adult psoriasis patients ages 18-65 with moderate to severe plaque psoriasis.High levels were greater than or equal to 140 pg/ml. Normal VEGF was below this level.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
PASI Change in Participants With Baseline VEGF Above 140 pg/ml and in Participants With Normal Baseline VEGF PASI Improved with normal VEGF	3 participants
PASI Change in Participants With Baseline VEGF Above 140 pg/ml and in Participants With Normal Baseline VEGF PASI Worsened with normal VEGF	0 participants
PASI Change in Participants With Baseline VEGF Above 140 pg/ml and in Participants With Normal Baseline VEGF PASI improved with high VEGF	1 participants
PASI Change in Participants With Baseline VEGF Above 140 pg/ml and in Participants With Normal Baseline VEGF PASI Worsened with high VEGF	2 participants
PASI Change in Participants With Baseline VEGF Above 140 pg/ml and in Participants With Normal Baseline VEGF PASI Unchanged with normal VEGF	1 participants

POST_HOC outcome

Timeframe: Week 16 to Week 28 and Week 28 to post study day 70

Population: 8 Adults ages 18-65 with moderate tosevere plaque psoriasis. 7 subjects studied. The 8th had SAE prior to Week 16.

Change in PASI from Week 16 after 16 weeks of adalimumab to Week 28 after another 12 weeks of adalimumab plus folic acid, vitamins B6 and B12 and Change reported by telephone 70 days after week 28

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=7 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
Psoriasis Change in Participants With High H. Pylori Titers and With Normal Titers. high titer worsened	1 participants
Psoriasis Change in Participants With High H. Pylori Titers and With Normal Titers. high titer improved then worsened day 70	1 participants
Psoriasis Change in Participants With High H. Pylori Titers and With Normal Titers. normal titer improved	3 participants
Psoriasis Change in Participants With High H. Pylori Titers and With Normal Titers. normal titer unchanged then improved day 70	1 participants
Psoriasis Change in Participants With High H. Pylori Titers and With Normal Titers. normal titer worsened	1 participants

POST_HOC outcome

Timeframe: Week 16 to Week 28

Population: 8 adults with moderate to severe plaque psoriasis ages 18-65. 4 were studied. Four were not because homocysteine levels at both Week16 nd 28 were not drawn(1 of the 4 had SAE prior to Week 16).

Change in EKG ( normalize, unchanged, became abnormal) when homocysteine (Hcy) increased or decreased from week 16 on adalimumab to week 28 on adalimumab plus folic acid, vitamins B6 and B12 in adault psoriasis patients ages 18-65 with moderate to severe plaque psoriasis.

Outcome measures

Measure	Humira Then Humira Plus 3 B Vitamins n=4 Participants Adults ages 18-65 with moderate to severe plaque psoriasis measured at week 16 after 16 weeks of adalimumab and week 28 after 16 weeks of adalimumab then 12 weeks of adalimumab plus 5 mg folic acid, 100 mg vitamin B6 and 1000 mcg of B12.
EKG Categoryy Changes Related to Homocysteine Changes unchanged when Hcy decreased	2 participants
EKG Categoryy Changes Related to Homocysteine Changes became abnormal when Hcy decreased	1 participants
EKG Categoryy Changes Related to Homocysteine Changes normalize when Hcy increased	1 participants

Adverse Events

Humira Then Humira Plus 3 B Vitamins

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Humira Then Humira Plus 3 B Vitamins n=7 participants at risk；n=8 participants at risk Pneumonia while on adaimumab and before the adalimumab plus B vitamins were begun.prior to vitamins
Infections and infestations Pneumonia	12.5% 1/8 • Number of events 1 • 2010-2013 On Humira alone: WBC elevation, Non specific st-t wave change and Left axis deviation. .

Other adverse events

Measure	Humira Then Humira Plus 3 B Vitamins n=7 participants at risk；n=8 participants at risk Pneumonia while on adaimumab and before the adalimumab plus B vitamins were begun.prior to vitamins
Cardiac disorders left axis deviation	28.6% 2/7 • Number of events 2 • 2010-2013 On Humira alone: WBC elevation, Non specific st-t wave change and Left axis deviation. .
Skin and subcutaneous tissue disorders psoriasis flare	42.9% 3/7 • Number of events 3 • 2010-2013 On Humira alone: WBC elevation, Non specific st-t wave change and Left axis deviation. .
Blood and lymphatic system disorders Elevated White blood count	14.3% 1/7 • Number of events 1 • 2010-2013 On Humira alone: WBC elevation, Non specific st-t wave change and Left axis deviation. .
Infections and infestations elevated Helicobacter pyori antibody	14.3% 1/7 • Number of events 1 • 2010-2013 On Humira alone: WBC elevation, Non specific st-t wave change and Left axis deviation. .
Cardiac disorders nonspecific st-t wave changes	14.3% 1/7 • Number of events 1 • 2010-2013 On Humira alone: WBC elevation, Non specific st-t wave change and Left axis deviation. .

Additional Information

Peter J. Aronson, MD

Dept. Dermatology Wayne StateUniversity

Phone: (313)_745-7845

Email: paronson@med.wayne.edu

Results disclosure agreements

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