No meaningful association between suicidal behavior and the use of IL-17A-neutralizing or IL-17RA-blocking agents

ABSTRACT

Introduction: An emerging class of agents blocking IL-17 signaling represents a very promising therapeutic approach. One of these agents, brodalumab, has been associated with an increased risk of suicide behavior.

Areas covered: This review sought to provide an overview strictly focused on suicide behavior signals related to the use of IL-17 agents. Data collection regarding this peculiar safety aspect was primarily based on: (i) a revision of safety outcomes belonging to phase II and phase III trials; (ii) a systematic search using the Pubmed Medline database; and (iii) collecting recent data issued as posters or communications in eminent international meetings.

Expert opinion: Whilst secukinumab and ixekizumab were not associated with increased signal of suicidal behavior, being recently approved for the treatment of psoriasis by EMA and FDA, brodalumab raised concern because of suicide behavior cases that led to pause momentarily its development program during pre-marketing stage before obtaining the positive recommendation by an FDA advisory panel for its approval. Indeed, a careful re-evaluation of brodalumab safety profile is being performed and no evidence clarified a significant association or a pathogenic mechanism linking brodalumab treatment to the risk of suicidal behavior, suggesting that cases of suicidal behavior accidentally occurred during brodalumab trials.

KEYWORDS:

• Brodalumab
• depression
• IL-17
• ixekizumab
• psoriasis
• secukinumab
• suicide

Article highlights

• The anti-IL-17 agents constitute the most recent developed class of therapeutics for the treatment of psoriasis and they demonstrated high efficacy.

• One of these agents, brodalumab, blocks the subunit A of the IL-17 receptor, and it has been associated with an increased risk of suicide behavior.

• Up to date, no pathogenic evidence links brodalumab use to psychiatric disorders.

• A re-evaluation of the clinical outcomes demonstrated no clinically meaningful association between suicide behavior and brodalumab use.

• An FDA expert panel, the Dermatologic and Ophthalmic Drugs Advisory Committee, evaluating brodalumab safety reports, considered the increased number of suicide behavior cases as only a suggestion of potential suicide risk, inducing its members to vote in favor of an FDA approval.

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Declaration of interest

A Chiricozzi and T Torres have received honoraria as speaker/consultant for Novartis (secukinumab manufacturer), Eli Lilly (ixekizumab manufacturer), Leo-Pharma (brodalumab commercial license holder in Europe).

Additional information

Funding

This paper was not funded.