QBrodalumab and Suicide: What does the Evidence Say?

Brodalumab, an IL-17 receptor blocker, is a safe and effective biologic therapy for plaque psoriasis. Brodalumab is unique within the IL-17 class in that it is the only agent which blocks the receptor, while other agents in the same class block IL-17A or IL-17A and IL-17F. Brodalumab has a U.S. Food and Drug Administration (FDA) Boxed Warning for suicidal ideation/behavior and therefore has an associated Risk Evaluation and Mitigation Strategy (REMS) program that is required when prescribing the medication.

In the worldwide phase III clinical trials for brodalumab, only 3 verified suicides were documented out 4,464 research subjects occurring in 2 research sites out of 390 research sites worldwide. The 3 patients who completed suicide had significant concurrent life stressors that may have contributed to their actions, including financial hardship, acute social isolation, and likely pending incarceration.

A recent research letter in the Journal of the American Academy of Dermatology (JAAD) used the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to evaluate the total number of completed suicides for psoriasis biologics using the worldwide post-marketing data¹. The authors found only one confirmed suicide with brodalumab in Japan despite nearly half a decade of worldwide use, and this patient may have only received one dose of brodalumab. Furthermore, this patient had a diagnosis of stage IV lung adenocarcinoma and who also lived isolated with no support system. Lastly, worldwide analysis of biologic agents for psoriasis in terms of the rate of completed suicides per total patient prescribed for each particular biologic found that brodalumab had a much less suicide rate as compared to adalimumab.

The FDA states the following in package insert for brodalumab, “a causal association between treatment with brodalumab and increased risk of suicidal ideation and behavior has not been established”. In a previous article written by me, my co-authors and I provide 9 reasons why this etiologic relationship is in question.² While further randomized, placebo-controlled double-blind studies are needed, considering all the facts presented above, brodalumab may not in fact increase risk of suicidality, despite the boxed warning.   

References:

1. Yeroushalmi S, Chung M, Bartholomew E, Hakimi M, Koo J. Examining worldwide postmarketing suicides from biologics used for psoriasis with a focus on brodalumab: A cross-sectional analysis using the Food and Drug Administration Adverse Event Reporting System (FAERS). JAAD Int. 2022;9:119. doi:10.1016/j.jdin.2022.08.010
2. Brodalumab for Treatment-Resistant Psoriasis: Case Reports and Safety Update – Nicholas D. Brownstone, Vidhatha Reddy, Quinn Thibodeaux, Stephanie Chan, Bridget Myers, Tina Bhutani, John Y.M. Koo, 2020. Accessed November 22, 2024. https://journals.sagepub.com/doi/abs/10.1177/2475530320925067?journalCode=jpsa