Brodalumab Versus Ustekinumab in Obese Patients With Moderate-to-Severe Plaque Psoriasis

Abstract

Introduction: Obesity is associated with psoriasis severity and decreased efficacy of psoriasis therapy.¹ Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.² This post hoc analysis evaluated clinical outcomes of treatment with brodalumab in obese versus nonobese participants with moderate-to-severe plaque psoriasis from phase 3 randomized controlled studies (AMAGINE-1/-2/-3).

Methods: Subgroups included in this analysis comprised obese (body mass index [BMI] ≥30 kg/m²) and nonobese participants (BMI <30 kg/m²) who received brodalumab 210 mg every 2 weeks (AMAGINE-1/-2/-3) or ustekinumab (AMAGINE-2/-3) through 52 weeks. Outcomes included psoriasis area and severity index 90% and 100% improvement (PASI 90 and 100) and treatment-emergent adverse events (TEAEs).

Results: AMAGINE-1 included 108 obese and 114 nonobese participants receiving brodalumab.³ At week 12, 59.3% and 27.8% of obese participants receiving brodalumab achieved PASI 90 and 100, respectively. Rates further improved by week 52 (PASI 90: 71.1%; PASI 100: 52.6%). At both time points, nonobese participants achieved higher rates of PASI 90 and 100 compared with obese participants. AMAGINE-2/-3 included 91 obese and 157 nonobese participants receiving brodalumab and 131 obese and 185 nonobese participants receiving ustekinumab.⁴ For obese participants receiving brodalumab, rates of PASI 90 and 100 were 74.7% and 49.5%, respectively, at week 12; these rates further improved by week 52 (PASI 90: 87.9%; PASI 100: 64.8%) and were higher compared with those of obese participants receiving ustekinumab (PASI 90: 76.3%; PASI 100: 51.9%). Indeed, regardless of BMI, the percentages of PASI 90 and 100 responders were greater with brodalumab compared with ustekinumab. By week 52, PASI responses were similar among nonobese and obese participants in each respective treatment group. Through 52 weeks, TEAEs per 100 patient-years were reported in participants receiving brodalumab (AMAGINE-1, obese: 370.8, nonobese: 388.7; AMAGINE-2/-3, obese: 366.3, nonobese: 404.4) and ustekinumab (AMAGINE-2/-3, obese: 420.6, nonobese: 366.5).

Conclusion: Regardless of BMI, brodalumab demonstrated sustained efficacy in participants with moderate-to-severe plaque psoriasis with no new safety signals.