6-Year Pharmacovigilance Data Suggests Brodalumab Safe for Psoriasis Despite Boxed Warning

Mark Lebwohl, MD

Credit: AMA

New 6-year pharmacovigilance data on brodalumab for moderate-to-severe psoriasis show consistency with the established safety findings on the medication observed in prior pharmacovigilance reports, new findings suggest, with no new completed or attempted suicide occurrences and a low rate of fungal infection.¹

These data were presented at the 44th Annual Fall Clinical Dermatology Conference in Las Vegas. The investigators of this research were led in part by Mark Lebwohl, MD, dean of clinical therapeutics at the Icahn School of Medicine at Mount Sinai.

Brodalumab is a biologic therapy designed to block the interleukin (IL)-17 receptor A and is approved for adult patients with moderate-to-severe psoriasis who are candidates for systemic options or phototherapy and have a failed response to other systemics. While there is not a confirmed causal link, the US prescribing guidelines for the medication include a boxed warning related to suicidal thoughts and behavior.²

This new analysis by Lebwohl and colleagues compiles pharmacovigilance data which has been reported by individuals within the US as well as healthcare providers to Ortho Dermatologics between August 2017 - August 2023. The team focused on the most commonly-reported adverse events (AEs) observed in the brodalumab package insert, known to occur in ≥1% of cases, as well as other key clinical events.

“In the brodalumab package insert, common AEs listed include arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection-site reactions, influenza, neutropenia, and Tinea infections,” Lebwohl et al. wrote.¹

AE rates which were reported were calculated by the investigators per 100 patients, with the research team dividing the total number of significant clinical events or AEs by the overall patient population which had been treated with brodalumab. They would then multiply by 100.

The investigators concluded that the crude rates of AE reporting for commonly-observed AEs had been comparable to rates noted in the 5-year report, with arthralgia being the most commonly-reported AE among patients during the 6-year pharmacovigilance analysis, followed by reports of headaches, fatigue, reactions at injection-site, and myalgia.

The team highlighted that since the 5-year mark, 2 additional cases of diarrhea and 1 additional case each of influenza, nausea, and oropharyngeal pain were noted. They added that associated crude reporting of AE rates were lower for year 6 compared with year 5.

Over the course of the 6-year timeframe, the investigators found that there were 13 cases of major adverse cardiovascular events (MACEs), all of which were determined through adjudication. They noted that 92% of these instances involved patients who were on cardiovascular medications, had pre-existing cardiovascular risk factors, or had related diagnoses or complications.

The research team added that following these individuals’ respective events, 54% continued their treatment with brodalumab. The MACEs overall instance rate for the study period was 0.25 per 100 patients, which is notably lower than the MACE rate seen in the Psoriasis Longitudinal Assessment and Registry (PSOLAR).

The team also looked at serious infections in the 6-year period, which they found occurred at a rate of 2.20 events per 100 patients. This represented a slight dip from the 5-year report’s rate of 2.23, with 1 additional Candida infection being documented since the report. They noted that the patient continued brodalumab therapy.

Additionally, there was a single new report of a serious fungal infection on a patient’s elbow in the sixth year; while the causality was not stated by the reporting individual, there was considered to be a possible causal link.

One subject did discontinue due to an instance of indeterminate inflammatory bowel disease (IBD), though this patient had a prior history of diarrhea.

Lastly, the research team found that over the entire 6-year period, there were 58 cases of depression that had been reported and a rate of 1.13 events per 100 patients. This was reported by the team to be marginally below the prior 5-year reporting rate of 1.14.

They concluded that within year 6, there were no additional suicide attempts, following a single attempt previously documented in year 3. Notably, the investigators found that there were no completed suicides across the 6 years of observation despite the boxed warning.

References

1. ^{Lebwohl M, Koo J, Armstrong A, Jacobson A, et al. Brodalumab: Six-Year US Pharmacovigilance Report. Presented at the 2024 Fall Clinical Dermatology Conference. Las Vegas, Nevada. 24-27 October.}
2. ^{Lebwohl M, Leonardi C, Armstrong A, Rawnsley N, Alexander B, Goehring E Jr, Kerdel F, Jacobson A. Three-year U.S. pharmacovigilance report of brodalumab. Dermatol Ther. 2021 Nov;34(6):e15105. doi: 10.1111/dth.15105. Epub 2021 Sep 5. Erratum in: Dermatol Ther. 2022 Sep;35(9):e15664. doi: 10.1111/dth.15664. PMID: 34418244; PMCID: PMC9286594.}