Comparable Efficacy and Safety of Brodalumab in Obese and Nonobese Patients With Psoriasis

Analysis of Two Randomized Controlled Trials

S. Hsu; L.J. Green; M.G. Lebwohl; J.J. Wu; A. Blauvelt; A.A. Jacobson


The British Journal of Dermatology. 2020;182(4):880-888. 

In This Article

Abstract and Introduction


Background: Obesity is associated with psoriasis and negatively affects response to therapy.

Objectives: To evaluate the efficacy and safety of brodalumab in nonobese vs. obese patients with psoriasis.

Methods: This is a post hoc analysis of the prospective, phase III, multicentre, randomized, placebo- and active-comparator-controlled AMAGINE-2 and AMAGINE-3 trials, in which patients were randomized to treatment with brodalumab 210 mg every 2 weeks, ustekinumab or placebo for a 12-week induction phase. At week 12, patients who received brodalumab 210 mg every 2 weeks continued brodalumab, those treated with ustekinumab continued ustekinumab, and those who received placebo switched to brodalumab 210 mg every 2 weeks. Patients were categorized by body mass index (BMI) category (< 30 or ≥ 30 kg m−2) and efficacy was evaluated using the physician-rated Psoriasis Area and Severity Index and static Physician's Global Assessment instruments.

Results: In total, 281 of 687 patients (40·9%) were obese. Skin clearance was comparable across BMI subgroups in brodalumab-treated patients. Psoriasis Area and Severity Index 100% improvement rates in nonobese and obese patients at week 12 were 54·1% and 49·5%, respectively, and at week 52 they were 72·6% and 64·8%, respectively. Week 12 ustekinumab responses were lower than brodalumab responses and were 6–17% lower in obese than in nonobese patients. No appreciable differences in overall safety were observed between nonobese and obese patients.

Conclusions: The efficacy and safety of brodalumab did not differ between patients with moderate-to-severe psoriasis who had a BMI < 30 kg m−2 or a BMI ≥ 30 kg m−2.


Obesity is known to increase the risk of developing psoriasis.[1–5] Meta-analytical data have shown that for every 5 kg m−2 increase in body mass index (BMI), a common measure of adiposity, the relative risk of developing psoriasis increases by 19%.[5] This association is strongest at higher BMI levels. The risk of developing psoriasis is nearly twofold greater among those who are obese (BMI ≥ 30 kg m−2) compared with nonobese individuals (BMI <30 kg m−2).[1] BMI has also been shown to correlate with psoriasis severity, with higher BMI linked to more severe disease.[6]

The effects of obesity on psoriasis extend beyond disease manifestation and can influence response to therapy. In 2010, the National Psoriasis Foundation recognized that obese patients were less likely to demonstrate a favourable response to systemic psoriasis therapies and were more likely to experience certain drug-specific side-effects (e.g. potential liver toxicity with methotrexate; nephrotoxicity with ciclosporin).[2] In part, the increased risk of side-effects may be related to higher doses of drugs with weight-based dosing.[7] Biologic therapies for psoriasis, which are often administered at fixed doses, tend to be less efficacious in obese patients; however, the effect is not uniform across all medications.[7–10] Given the established potential for differing response in obese vs. nonobese patients, it is important to understand the influence of obesity on the efficacy and safety of new and emerging psoriasis treatments.

Brodalumab is a fully human, anti-interleukin-17 receptor A (IL-17RA) monoclonal antibody that was approved in 2017 for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy.[11] In clinical trials, brodalumab treatment resulted in significant skin clearance and improvement in signs and symptoms of psoriasis.[12,13] The analysis reported herein used pooled data from two large, phase III, multinational studies to evaluate the effect of BMI – nonobese (BMI < 30 kg m−2) or obese (BMI ≥ 30 kg m−2) – on the efficacy, safety and tolerability of brodalumab and an active comparator (ustekinumab) in patients with moderate-to-severe plaque psoriasis.