Efficacy of Adalimumab Compared With Methotrexate or Placebo Stratified by Baseline BMI in a Randomized Placebo-Controlled Trial in Patients With Psoriasis
August 2015 | Volume 14 | Issue 8 | Original Article | 864 | Copyright © August 2015
Ronald Prussick MD,a Kristina Unnebrink PhD,b Wendell C. Valdecantos MDc
aDepartment of Dermatology, George Washington University, Washington, DC, USA
bData and Statistical Sciences, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany
cImmunology – Dermatology, Global Medical Affairs, AbbVie Inc., North Chicago, IL,USA
INTRODUCTION: In the Comparative Study of Humira vs Methotrexate vs Placebo In Psoriasis Patients (CHAMPION) study, significantly
more patients achieved ≥75% improvement in the Psoriasis Area and Severity Index (PASI75) and ≥90% improvement (PASI90) after 16 weeks of treatment with adalimumab (80 mg at week 0, then 40 mg every other week starting at week 1) compared with methotrexate (up to 25 mg/week orally) or placebo. In this exploratory analysis, the efficacy of adalimumab was evaluated in a subset of the CHAMPION patient population stratified by baseline body mass index (BMI).
METHODS: PASI responses and Dermatology Life Quality Index (DLQI) scores through 16 weeks of treatment were examined by baseline BMI category (<25 kg/m2
[normal], 25 to <30 kg/m2
[overweight], and ≥30 kg/m2
[obese]) in patients with psoriasis with a baseline PASI total score ≥12. Treatment differences between the adalimumab and the methotrexate or placebo groups were compared using Fisher’s exact test for PASI responses and 1-way analysis of variance for DLQI scores.
RESULTS: In all BMI categories, adalimumab treatment led to significantly greater rates of PASI75/90 responses at weeks 12 and 16 compared with methotrexate or placebo (P<0.05 for all). In normal weight, overweight, and obese patients at week 16, the respective PASI75 response rates were 85.0%, 85.7%, and 61.3% with adalimumab; 43.3%, 29.3%, and 26.1% with methotrexate;
and 28.6%, 16.7%, and 0% with placebo. PASI90 response rates were 70.0%, 53.6%, and 35.5% with adalimumab; 26.7%, 7.3%, and 8.7% with methotrexate; and 9.5%, 16.7%, and 0% with placebo. Across all BMI subgroups, the greatest decreases in DLQI scores from baseline occurred in the adalimumab group.
CONCLUSION: Significantly higher PASI75/90 response rates and more pronounced improvements in DLQI scores at week 16 were identified in patients treated with adalimumab, compared with methotrexate or placebo, regardless of baseline BMI category. J Drugs Dermatol.
It is estimated that approximately 7.4 million adults in the United States are affected by psoriasis.1 Adalimumab, a tumor necrosis factor (TNF) inhibitor, has been approved for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.2 The safety, tolerability, and efficacy of adalimumab in the treatment of moderate to severe psoriasis has been demonstrated in randomized, double-blind clinical trials and open-label extension studies, including the Comparative Study of Humira vs Methotrexate vs Placebo In Psoriasis Patients
Multiple studies have identified a relationship between obesity and psoriasis, and some have suggested that obesity is associated with increased disease severity.7,8 Additionally, analyses have shown that the efficacy of various psoriasis treatments may be dependent on body mass index (BMI), resulting in diminished treatment responses
in heavier patients compared with their normal weight counterparts.9-11 In this report, the effect of BMI on the efficacy of adalimumab in patients participating in the CHAMPION study is examined.
The full details of the CHAMPION study (ClinicalTrials.gov identifier: NCT00235820) have been previously reported.3 Briefly, it was a randomized, double-blind, placebo-controlled, phase 3 study conducted at 28 sites in Europe and Canada. Men and women, aged ≥18 years, with moderate to severe plaque psoriasis for at least 1 year who were candidates for systemic therapy or phototherapy and naive to TNF therapy and methotrexate were randomized in a 2:2:1 ratio to receive adalimumab by subcutaneous injection (80 mg at week 0, then 40 mg every other week starting at week 1), methotrexate (up to 25 mg/week orally), or placebo for 16 weeks. All patients also received oral folate supplements