Efficacy and safety of brodalumab in patients with psoriasis who had inadequate responses to ustekinumab: subgroup analysis of two randomized phase III trials

Background Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has demonstrated superior efficacy and safety over ustekinumab as induction therapy for moderate-to-severe psoriasis. Objectives To evaluate the efficacy and safety of brodalumab through week 52 in patients who had inadequate responses to ustekinumab. Methods A subgroup analysis of the phase III AMAGINE-2/-3 double-blind randomized controlled trials was performed. Participants were aged 18-75 years and had a Psoriasis Area and Severity Index (PASI) >= 12, static Physician's Global Assessment score >= 3 and involvement of >= 10% body surface area. The studies were registered at ClinicalTrials.gov: AMAGINE-2, NCT01708603; AMAGINE-3, NCT01708629. Results At baseline, patients with or without prior biologic experience who had an adequate response at week 16 on ustekinumab or brodalumab had lower rates of involved body surface area, PASI, prior biologic use, psoriatic arthritis and body mass index than patients who experienced inadequate response at or after week 16. Among patients who experienced inadequate response to ustekinumab, those rescued with brodalumab had PASI >= 75%, >= 90% and 100% improvement response rates of 72 center dot 6%, 58 center dot 1% and 36 center dot 3%, respectively, at week 52 compared with 61 center dot 7%, 25 center dot 5% and 5 center dot 4%, respectively, in patients who continued ustekinumab. Exposure-adjusted rates of treatment-emergent adverse events were similar among patients rescued with brodalumab (377 center dot 3 adverse events per 100 patient-years) and those who remained on ustekinumab (389 center dot 9 adverse events per 100 patient-years). Conclusions Among patients who experienced inadequate responses to ustekinumab, rescue with brodalumab improved skin clearance outcomes compared with continuing ustekinumab.