Efficacy and Safety of Adalimumab among Patients with Moderate to Severe Psoriasis with Co-Morbidities Subanalysis of Results from a Randomized, Double-Blind, Placebo-Controlled, Phase III Trial

Background: Psoriasis is associated with a variety of major physical and mental co-morbidities. Objective: To assess the incremental burden of co-morbidities on patient-reported outcomes and evaluate the efficacy and safety of adalimumab in psoriasis patients with co-morbidities. Study Design: Data were obtained from the initial 16-week, double-blind treatment period of REVEAL (Randomized controlled EValuation of adalimumab Every other week dosing in moderate to severe psoriasis triAL), a randomized, multicenter, phase III clinical trial. Intervention: Patients with moderate to severe psoriasis were randomized in a 2:1 ratio to receive adalimumab 80 mg (two 40 mg injections administered subcutaneously) at baseline followed by one 40 mg injection every other week from week 1 to week 15 or placebo. Main Outcome Measures: Clinical severity (Psoriasis Area and Severity Index [PAST]) and patient-reported outcomes (Dermatology Life Quality Index [DLQI], Short Form 36 [SF-36] health survey, Work Productivity and Activity Impairment [WPAI] questionnaire) were assessed during the trial. The effect of selected co-morbidities (i.e. hypertension, psoriatic arthritis, hyperlipidemia, obesity, depression, other forms of arthritis, diabetes mellitus, and other cardiovascular diseases) on patient-reported outcomes was evaluated using multivariate analysis of covariance models. Subgroup analyses were performed by comorbidity type to statistically compare the clinical efficacy, patient-reported outcome benefits, and safety of adalimumab with placebo in the presence of these conditions. Results: Study co-morbidities were each independently associated with significantly greater impairment on at least one general patient-reported outcome measured at baseline (all p<0.05), with the exception of hyperlipidemia. During the 16-week study, adalimumab patients demonstrated significantly greater PAST 75 response rates (defined as a reduction of at least 75% in PAST scores from baseline) compared with placebo patients for all co-morbidity subgroups. Adalimumab provided consistent improvements in DLQI, SF-36 Physical Component Summary and Mental Component Summary scores, and WPAI total scores from baseline to week 16 within comorbidity subgroups. Rates of serious adverse events (AEs), serious infectious AEs, and AEs leading to discontinuation were comparable between adalimumab and placebo for patients with co-morbidities. Conclusions: Co-morbidities were associated with additionally impaired health-related quality of life and work productivity in patients with psoriasis. Adalimumab significantly improved efficacy and patient-reported outcomes and was well tolerated in patients with co-morbidities.