Brodalumab: A Review of Safety

Sina Rusta-Sallehy, BHSc; Melinda Gooderham, MD, MSc, FRCPC; Kim Papp, MD, PhD, FRCPC

Disclosures

Skin Therapy Letter. 2018;23(2):1-3. 

In This Article

Abstract and Introduction

Abstract

Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab, the third commercially available IL-17 antagonist, was approved by the US FDA in February 2017 for the treatment of moderate-to severe plaque psoriasis. As brodalumab enters the marketplace, it is imperative to investigate its safety profile. We conducted a safety assessment of brodalumab using publicly available adverse event data from phase II and III clinical trials. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and candidiasis. The FDA issued a black box warning after six patients treated with brodalumab across four clinical trials committed suicide, but no causal relationship was identified. Current evidence suggests a similar safety profile for brodalumab compared to other IL-17 antagonists used to treat moderate-to-severe plaque psoriasis.

Introduction

Interleukin (IL)-17 is important in the pathophysiology of psoriasis and has proven to be an effective therapeutic target. Brodalumab is an IL-17R inhibitor[1] evaluated in rheumatoid arthritis,[2] Crohn's disease,[3] and psoriatic arthritis,[4] and is approved for the treatment of moderate-to-severe, chronic plaque psoriasis in Japan, US, and Europe. Development in rheumatoid arthritis was stopped for futility.[2] The Crohn's disease program was terminated as a trend to worsening of disease was observed in a phase II study.[3] Amgen terminated the psoriasis and psoriatic arthritis programs for commercial reasons,[5] however, sufficient data had been collected for submission to regulatory agencies for approval. Brodalumab was approved by the Japanese Pharmaceuticals and Medical Devices Agency in July 2016 (Lumicef®), the US FDA in February 2017 (Siliq™), and the European Medicines Agency in July 2017 (Kyntheum®) for treatment of moderate-to-severe plaque psoriasis.

Given the mechanism of action, the anticipated safety profile of brodalumab should reflect that of other IL-17 blockers. More controversial is the posited reason for abandoning the psoriasis and psoriatic arthritis program. A numerical imbalance in the number of suicides occurring in patients receiving brodalumab compared to placebo was observed, which would affect the labelling requirements.,[6,7] Herein, we review the publicly available safety data for brodalumab across the entire development program.

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