title: No meaningful association between suicidal behavior and the use of IL-17A-neutralizing or IL-17RA-blocking agents.
abstract: 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.
authors.affiliation: a Dermatology Department , University of Pisa , Pisa , Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Chiricozzi
authors.affiliation: a Dermatology Department , University of Pisa , Pisa , Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Romanelli
authors.affiliation: b Dermatology Department , University of Tor Vergata , Rome , Italy.
authors.forename: Rosita
authors.initials: R
authors.lastname: Saraceno
authors.affiliation: c Department of Dermatology, Centro Hospitalar do Porto and Instituto de Ciências Biomédicas Abel Salazar , University of Porto , Porto , Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Torres
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors*; D011565:Psoriasis / Q000188:drug therapy; D013405:Suicide / Q000706:statistics & numerical data*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C508717:IL17A protein, human; D020381:Interleukin-17; C571216:brodalumab; C549079:ixekizumab; C555450:secukinumab
keywords: Brodalumab; IL-17; depression; ixekizumab; psoriasis; secukinumab; suicide