Efficacy and Safety of Brodalumab in Patients With Psoriasis Who Had Inadequate Responses to Ustekinumab

Subgroup Analysis of Two Randomized Phase III Trials

R.G. Langley; A.W. Armstrong; M .G. Lebwohl; A. Blauvelt; ; S. Hsu; S. Tyring; S. Rastogi; R. Pillai; R. Israel


The British Journal of Dermatology. 2019;180(2):306-314. 

In This Article

Abstract and Introduction


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 72·6%, 58·1% and 36·3%, respectively, at week 52 compared with 61·7%, 25·5% and 5·4%, respectively, in patients who continued ustekinumab. Exposure-adjusted rates of treatment-emergent adverse events were similar among patients rescued with brodalumab (377·3 adverse events per 100 patient-years) and those who remained on ustekinumab (389·9 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.


Psoriasis is a chronic, systemic, immune-mediated inflammatory disease that affects approximately 1–8·5% of adults worldwide.[1] Psoriatic tissue inflammation is characterized by excess of inflammatory cytokines, particularly overexpression and activation of members of the interleukin (IL)-17 family of cytokines.[2,3] These cytokines, specifically IL-17A, IL-17C and IL-17F, are produced by T helper (Th)17 cells and innate immune cells.[4] IL-23 is an upstream regulatory cytokine that activates and promotes survival of Th17 cells.[5]

Brodalumab is a fully human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that selectively targets IL-17RA and blocks the effects of several IL-17 cytokine family members, including IL-17A, IL-17F, IL-17A/F and IL-25.[2] The efficacy and safety of brodalumab have been established in a clinical trial programme that included three large phase III trials: AMAGINE-1, AMAGINE-2 and AMAGINE-3.[6,7] In AMAGINE-2/-3, both of which included ustekinumab (a monoclonal antibody to the p40 subunit of IL-12 and IL-23) as an active comparator, > 50% of patients receiving brodalumab had complete clearance of psoriasis [i.e. 100% reduction from baseline in Psoriasis Area and Severity Index (PASI 100)] within 1 year of treatment compared with 29–30% for ustekinumab.[6,7] The onset of skin clearance was also faster in patients treated with brodalumab 140 mg or 210 mg every 2 weeks (Q2W) compared with ustekinumab, with differences in speed of efficacy evident by week 1.[8]

Understanding the efficacy and safety of brodalumab in patients with and without prior exposure to biologics is important for clinicians to inform treatment decisions. It is especially useful to determine the efficacy and safety of brodalumab in patients who had inadequate responses to other biologics. Therefore, we undertook this analysis of patients in AMAGINE-2/-3 initially randomized to ustekinumab who were switched to brodalumab 210 mg Q2W at week 16 after experiencing inadequate responses to ustekinumab.