New pharmacovigilance data on psoriasis drug brodalumab shows that over 4 years its safety data aligned with the drug's established safety profile, according to new findings presented at Society of Dermatology Physician Assistants (SDPA) 2023 Annual Summer Dermatology Conference.¹

The safety of brodalumab—an interleukin-17 receptor A antagonist—has been a subject of interest recently, given its boxed warning regarding suicidal ideation and behavior in the US. As a result, this research was conducted for further examination.

This study, led by Mark Lebwohl, MD, from the Icahn School of Medicine at Mount Sinai, and colleagues, aimed to review the current pharmacovigilance data in the US over the course of a 4-year reporting period and to allow for further insight into brodalumab’s safety in treating adult patients with moderate-to-severe plaque psoriasis.

Ortho Dermatologics compiled pharmacovigilance data reported by both patients and healthcare providers from August of 2017 - August of 2021. The research team’s analysis focused on adverse events (AEs) commonly listed in the brodalumab package insert and AEs of special interest.

Within brodalumab’s package insert, the most frequent AEs were described by the investigators as being (with incidence of ≥1%) headache, arthralgia, myalgia, diarrhea, oropharyngeal pain, influenza, nausea, injection-site reactions, neutropenia, fatigue, and Tinea infections.

The research team examined AEs which were of special interest as exposure-adjusted rates per 100 patient-years (PYs).

“Brodalumab exposure was estimated as the time between the first and last prescription-dispensing authorization dates,” Lebwohl and colleagues wrote. “Patients with the same initial and last prescription-dispensing authorization date were excluded.”

The data encompassed 4019 US patients with an estimated exposure of 4563 PYs. Of the 2118 unique AE cases reported, 22% originated from healthcare providers, while the remaining 78% were reported directly by patients.

Consistent with previous reports, arthralgia emerged as the most frequently reported AE during the 4-year reporting period, with an incidence rate of 2.52 events per 100 PYs. Among the cases of arthralgia, 53 patients continued treatment, 25 discontinued, and the treatment status of 37 patients remained unknown. Notably, among the four new cases of arthralgia reported since the 3-year analysis, three patients experienced joint pain while temporarily off brodalumab.

Furthermore, the investigators reported that zero new cases of injection-site reactions, neutropenia, or fatigue were reported since the prior 3-year analysis. Most importantly, over the entire 4-year reporting span, they noted that there were no completed suicides attributed to the drug’s use as well as no new cases of suicide attempts being reported after the 3-year analysis.

Regarding infections, out of 102 serious infections reported, only 3 were deemed to be associated with brodalumab. Notably, no serious fungal infections were reported by the research team, although 1 new fungal infection case (onychomycosis) resulted in discontinuation of brodalumab.

Additionally, the investigators reported no new reports of oral candidiasis. In terms of inflammatory bowel disease, no new cases of Crohn's disease were identified, with a single previously reported case occurring in 1 patient with a symptomatic history predating brodalumab initiation.

Additionally, a single case of ulcerative colitis, not suspected to be related to the drug, was reported by the research team. As for malignancies, a total of 37 cases were reported in 32 patients, though none of them were found to be associated with brodalumab.

In sum, the US pharmacovigilance data examined in this assessment matches that of the previously-established safety profile of brodalumab, as observed in several long-term clinical trials and prior 3-year reports.

Notably, the absence of completed suicides over the 4-year reporting period, despite the boxed warning for suicidal behavior and ideation, further supports the idea that no causal relationship between the drug and tendencies for suicide is evident.

Overall, The findings reinforce the established safety profile of brodalumab and support its continued use as an effective therapeutic option, with no new safety concerns identified during the extended surveillance period.

References

1. ^{Lebwohl M, Koo J, Leonardi C, Armstrong A, Rawnsley N, Goehring E, Jacobson A. Brodalumab: 4-Year US Pharmacovigilance Report. J Drugs Dermatol. 2023 Apr 1;22(4):419-422. doi: 10.36849/JDD.7344. PMID: 37026879.}