Brodalumab treatment does not cause suicidality in patients with psoriasis
There is no causal relationship between suicidality and treatment with brodalumab, according to data from five clinical trials.
A total of 4,464 patients with psoriasis with 9,161.8 patient-years of brodalumab exposure were included in the analysis. Throughout the 52-week controlled phases, the brodalumab and ustekinumab groups showed comparable follow-up time‒adjusted incidence rates of suicidal ideation and behaviour (SIB) events (0.20 vs 0.60 per 100 patient-years). [J Am Acad Dermatol 2018;78:81–89.e5]
“Given the prevalence of SIB risk factors among individuals with psoriasis and at baseline in brodalumab clinical trials, it is not surprising that SIB events occurred in the brodalumab trials and that most patients with SIB events during the brodalumab trials had a history of predisposing risk factors,” researchers said. [Arch Dermatol 2010;146:891–895; J R Soc Med 2014;107:194–204; J Invest Dermatol 2015;135:984–991; J Int Med Res 2016;44:61–66]
Brodalumab showed a similar rate of SIB events with those observed with placebo or ustekinumab during the induction phase, and to that with ustekinumab during the first year of treatment. Psychiatric adverse events (AEs) were also similar in patients receiving brodalumab and in those receiving placebo over 12 weeks as well as in patients receiving ustekinumab over 12 and 52 weeks.
Four completed suicides occurred in the brodalumab group over a total of 9,161.8 patient-years. One of these was later decided as indeterminate. All patients presented with underlying psychiatric disorders or stressors.
“The rates of suicidal behaviour AEs or completed suicides did not increase over time in the brodalumab treatment group,” researchers noted. “These observations highlight the lack of evidence of a causal relationship between brodalumab and SIB.”
There were specific exclusion criteria for psychiatric disorders or substance abuse in most clinical trials of systemic drugs for moderate-to-severe psoriasis, but such criteria in the brodalumab studies were limited to more closely represent the general psoriasis patient population, allowing patients with SIB risk factors at baseline to participate, researchers said.
“Even with more restrictive exclusion criteria, SIB events have been reported in clinical trials of other agents used to treat psoriasis, including adalimumab, apremilast, certolizumab, ixekizumab, secukinumab, and ustekinumab,” researchers said. [J Drugs Dermatol 2016;15:1192–1196; Celgene Corporation, Summit, NJ; 2014; UCB, Inc, Smyrna, Georgia; 2016; Br J Dermatol 2013;168:844–854; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/125521Orig1s000SumR.pdf; https://www.pharmamedtechbi.com/∼/media/Supporting%20Documents/The%20Pink%20Sheet%20DAILY/2014/October/101614%20Novartis%20briefing%20docs.pdf]
Researchers analysed data from the following: a placebo-controlled, phase II clinical trial; the open-label, long-term extension of the phase II clinical trial; and three phase III, randomized double-blind, controlled clinical trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3) and their open-label, long-term extensions of patients with moderate-to-severe psoriasis.
This study was limited by the absence of a comparator arm past week 52. Also, controlled study periods were not powered to detect differences in rare events such as suicide.
“Prescribers are encouraged to weigh the potential risks and benefits of brodalumab treatment in patients with a history of depression or SIB,” researchers said. “To assess a potential correlation between SIB and treatment of psoriasis, future studies should be adequately powered and patient SIB risk factors balanced at baseline.”