Open Label Study of Adalimumab in Subjects Who Have a Sub-optimal Response to Systemic Therapy or Phototherapy

Study Overview
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Brief Summary
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The objective of this study was to evaluate the safety and efficacy profile of Humira (adalimumab) in patients who had a sub-optimal response to prior systemic therapy. This open-label study was conducted in a patient population of moderate to severe chronic plaque psoriasis patients, which is an approved patient population for adalimumab.

Detailed Description
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This 16-week multicenter, open-label study was designed to evaluate the efficacy and safety of a loading dose of 80 mg adalimumab, followed by 40 mg adalimumab every other week in the treatment of psoriasis in patients with a sub-optimal response to etanercept, methotrexate (MTX), or Narrow band Ultraviolet - B (NB-UVB). Approximately 150 participants were planned for 3 sub-studies: 80 participants with sub-optimal response to etanercept, 40 participants with sub-optimal response to MTX, and 30 participants with sub-optimal response to NB-UVB. Actual enrollment was 82 participants with sub-optimal response to etanercept, 41 participants with sub-optimal response to MTX, and 29 participants with sub-optimal response to NB-UVB. Screening was performed at least 96 hours and no more than 31 days before the Baseline visit (Week 0). A participant who was eligible for the study based on sub-optimal response to one treatment (MTX, NB-UVB, or etanercept) was required to discontinue that treatment within a specified time before first dose of adalimumab (see descriptions of sub-study groups). In addition, if the participant was also receiving another qualifying treatment, he/she was required to have discontinued the other treatment at least 30 days before the Baseline visit (Week 0). Adalimumab was administered by subcutaneous (SC) injection. At the Baseline Visit (Week 0), all participants received an initial dose of 80 mg adalimumab SC. Every other week (odd-numbered weeks) from Week 1 to Week 15, participants received 40 mg adalimumab SC. This was a single group assignment study, that is, all participants received the same treatment; however, data were summarized for 3 groups (sub-studies) that were defined by psoriasis treatments participants received before entering this study: methotrexate, etanercept, or narrow-band, ultraviolet-B. Efficacy was evaluated using the Physician's Global Assessment (PGA) of disease severity, and patient-reported outcomes: Patient's Global Assessment (PTGA) of disease severity, the Psoriasis-related Pruritus Assessment, the Dermatology Life Quality Index (DLQI), a visual analog scale (VAS) for plaque psoriasis and psoriatic arthritis pain, the Medical Outcomes Study (MOS) Sleep Scale, and the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI: SHP). Serious and nonserious adverse events were summarized by sub-study of participants (suboptimal response to MTX, suboptimal response to NB-UVB, and suboptimal response to etanercept).

Official Title
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Open Label Study of Adalimumab in Subjects Who Have a Sub-optimal Response to Systemic Therapy or Phototherapy

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: adalimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of chronic plaque psoriasis with disease duration of at least 6 months Sub-optimal response to treatment with etanercept, methotrexate, or narrow-band UVB phototherapy Exclusion Criteria: Prior treatment with adalimumab Multiple concomitant therapy restrictions and/or washouts (topicals, ultraviolet, other systemic psoriasis therapies) Prior treatment with natalizumab Concurrent active skin diseases/infections Poorly controlled medical conditions History of neurologic symptoms suggestive of central nervous system (CNS) demyelinating disease History of certain cancers

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Open Label<br> | Biological: adalimumab<br>* Participants received an 80 mg adalimumab loading dose by subcutaneous injection at Baseline (Week 0). From Week 1 to Week 15, participants received 40 mg adalimumab by subcutaneous injection every other week.<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Achieved a Physician's Global Assessment (PGA) of Clear (0) or Minimal (1) at Week 16 | The PGA is a 6-point scale used to measure the severity of a patient's disease. Plaque elevation, scaling, and erythema are rated from 0= clear (no plaque elevation; no scaling; erythema=hyperpigmentation, pigmented macules, diffuse faint pink or red coloration) to 5=very severe (plaque elevation=very marked; scaling=very coarse; erythema=very severe [extreme red coloration, dusky to deep red coloration]). | Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving a PGA of Clear (0) at Week 16 |  | Week 16 | 
| Number of Participants Achieving at Least 1 Grade of Improvement in PGA at Week 16 Compared to Screening |  | From Screening to Week 16 | 
| Number of Participants Achieving 0 or 1 on Patient's Global Assessment at Weeks 2, 4, and 8 | The Patient's Global Assessment of Psoriasis-Severity is a rating of how well their disease is controlled. 0=complete disease control; 1=good disease control; 2=limited disease control; 3=uncontrolled disease. | Weeks 2, 4, and 8 | 
| Dermatology Life Quality Index (DLQI) Total Score | The DLQI has 10 items and 6 subscales: symptoms and feelings (Q 1 and 2), daily activities (Q 3 and 4), leisure (Q 5 and 6), work and school (Q 7), personal relationships (Q 8 and 9), and treatment (Q 10). Participants rate how much their skin problem affected their life in previous week. Responses are 0 (not at all) to 3=very much. DLQI=total of scores for all items; max=30; min=0. | From Screening to Week 4 and Week 16 | 
| Number of Participants Achieving DLQI Total Score of 0 at Week 4 and Week 16 | DLQI total score of 0 indicates psoriasis had no effect at all on participant's life. | Week 4 and Week 16 | 
| Psoriasis-related Pruritus Assessment | The Psoriasis-related Pruritus Assessment is a scale for evaluating pruritus-related to psoriasis over the previous week; values range from 0 (no itching) to 10 (severe itching). A decrease in score indicates an improvement in pruritus. | From Screening to Week 16 | 
| Visual Analog Scale (VAS) for Pain Involving Psoriatic Plaques and/or Psoriatic Arthritis | The participant rates his/her pain during the previous week on a 100 mm VAS, from 0=no pain to 100=pain as bad as it could be. A decrease in score indicates improvement. | From Screening to Week 16 | 
| Percent Work Time Missed Due to Psoriasis | Work and activity impairment due to psoriasis were evaluated using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP), a 6-item questionnaire that measures effect of psoriasis on number of hours worked and the number of hours missed from work. It also measures the effect on productivity and regular activities: 0=no effect on work/daily activities; 10=psoriasis prevented me from working/doing daily activities. Decreases in values on each part indicate improvement. At Screening, percent time missed in the previous week ranged from 0% to 40%. | From Screening to Week 16 | 
| Percent Overall Work Impairment Due to Psoriasis | Percent overall work impairment was evaluated using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP) (described above). At Screening, overall impairment ranged from 0% to 94%. A decrease in percent overall work impairment indicates improvement. | From Screening to Week 16 | 
| Percent Impairment While Working Due to Psoriasis | Percent impairment while working was evaluated using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP), described above. At Screening, impairment while working ranged from 0% to 90%. A decrease in percent impairment indicates improvement. | From Screening to Week 16 | 
| Percent Activity Impairment Due to Psoriasis | Percent impairment in regular activities was evaluated using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI-SHP), described above. At Screening, activity impairment due to psoriasis ranged from 0% to 90%. | From Screening to Week 16 | 
| Sleep Problems Index II | Sleep Problems Index of the Sleep Scale from the Medical Outcomes Study reflects sleep disturbance, perceived sleep adequacy, daytime somnolence, and awakening short of breath or with headache. Participant rates each item from none of the time to all of the time for the previous 4 weeks. Scores are transformed to 0 to 100 scale; lower scores indicate less impairment. Decrease in score indicates improvement. | From Screening to Week 16 |