Brodalumab Demonstrates Efficacy, Safety in Moderate to Severe Psoriasis

Kim Papp, MD, PhD

Credit: Arcutis

Brodalumab—an interleukin (IL)-17 receptor A blocker—was shown to be a safe and effective treatment option for patients with moderate to severe psoriasis who had an inadequate response to prior biologics, according to data presented at the SDPA Annual Summer Dermatology Conference.1 More than half of patients enrolled in the trial achieved clinically relevant improvements as determined by static physician’s global assessment (sPGA) ratings and the psoriasis area and severity index 90% improvement (PASI 90) from baseline.

Previous phase 3 data from AMAGINE-2 and AMAGINE-3 revealed approximately 35% of patients who failed ≥ 1 biologic were able to achieve PASI 100 after 16 weeks of treatment with brodalumab.

To determine the safety and efficacy of the drug for the treatment of patients with moderate to severe psoriasis, a team of investigators led by Kim Papp, MD, PhD, associated with Probity Medical Research in Waterloo, Ontario, Canada, and the University of Toronto, analyzed data from 2 phase 4, multicenter, open-label studies conducted in Canada and the United States (US). The Canadian study recruited patients with an inadequate response to ≥ 1 biologic, including IL-17, IL-23, IL-12/23, or tumor necrosis factor (TNF)-α, whereas the US study enrolled patients with an inadequate response to ≥ 1 anti-IL-17A biologic.

Patients were treated with a subcutaneous injection of brodalumab 210 mg at weeks 0, 1, and 2, and then every 2 weeks until week 26 (Canadian study) or week 16 (US study). The primary outcome was the percentage of patients able to achieve PASI 75, 90, and 100 and the percentage of patients achieving an sPGA rating of 0 (clear) or 1 (almost clear). Additional endpoints were the percentage change from baseline in the dermatology life quality index (DLQI) and the psoriasis symptom inventory (PSI). Efficacy data was reported at week 16 to ensure consistency across both studies; however, the safety data was reported separately at weeks 26 and 16, depending on the study.

In the 26-week Canadian study, 251 adult patients were enrolled with a baseline mean PASI of 10.2 and a most had a sPGA rating of 3, indicating moderate activity (77.3%; n = 194). Almost half of patients were previously treated with an anti-IL-17 biologic (45.4%, n = 114). The American study enrolled 39 adult patients with a mean baseline PASI of 20.4 and a mean sPGA score of 3.4. The US cohort was nonresponsive to an average of 2 prior anti-IL-17A biologics.

Overall, 189 (74.1%) patients treated with brodalumab achieved PASI 75, 133 (52.2%) achieved PASI 90, and 98 (38.4%) achieved PASI 100. In the Canadian study, the percentage changes from baseline to week 16 regarding DLQI and PSI were -67.6% (95% confidence interval [CI]: -73.5%, -61.7%; n = 212) and -64.4% (95% CI: -70.5%, -58.3%; n = 216), respectively. Additionally, 69% (n = 176) of patients were able to reached an sPGA of 0 or 1.

The rates of treatment-emergent adverse events (TEAEs) were comparable to the established safety profile of the drug with no new safety signals identified in the Canadian study. Although 64.9% (n = 163) of patients reported ≥ 1 TEAE, most were categorized as mild or moderate in severity. Only 4.4 (n = 11) experienced ≥ 1 serious TEAE.

In the US study, only 6 (15.4%) patients experienced a TEAE, none of which were thought to be related to brodalumab treatment and none were categorized as serious. Adverse events included prediabetes, corneal ulcer, tooth abscess, sciatica, folliculitis, and allergic sinusitis.

“Brodalumab has a broad mechanism of action and inhibits multiple proinflammatory cytokines involved in the pathogenesis of psoriasis, which may contribute to its efficacy,” wrote investigators.

References

1. ^{Papp K,Lebwohl M, Armstrong, A, Desai S, et al. Efficacy and Safety of Brodalumab in Patients With Moderate-to-Severe Plaque Psoriasis and Inadequate Response to Prior Biologics. Poster presented at: SDPA Annual Summer Dermatology Conference. San Diego, CA. June 5 – 9, 2024.}