Brodalumab Performs in Phase 4 Studies of Moderate to Severe Psoriasis

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Results from two phase 4 open label trials of patients with moderate to severe psoriasis with inadequate response to previous biologics found brobdalumab resulted in clinically relevant improvement, according to a poster presented at the 2024 Society for Dermatology Physician Assistants Annual Summer Dermatology Conference in San Diego, California.¹

Participants in the US phase 4 study (NCT03403036) were adults with moderate to severe psoriasis (N = 39) who had inadequate response to at least 1 anti- anti-interleukin (IL)-17A biologic, although on average, patients had inadequate response on 2 anti-IL-17A biologics. Upon enrollment, patients had a mean PASI of 20.4, while the mean Static Physician’s Global Assessment (sPGA) was 3.4.

The Canadian phase 4 study (NCT04149587) similarly included adults with moderate to severe psoriasis (N = 251). About three-quarters of the patients scored a 3 on sPGA, and the mean PASI was 10.2. The Canadian study included participants who had inadequate response to at least 1 biologic targeting either IL-17, IL-23, IL-12/23, or tumor necrosis factor α (TNF-α). About half of the participants had received an anti-IL-17 biologic.

Patients in both studies received subcutaneous injection of brodalumab 210 mg at weeks 0, 1, and 2 and then every 2 weeks until the endpoint. The US study concluded at 16 weeks while the Canadian study concluded at 26 weeks. Kim Papp, MD, PhD, and colleagues looked at the percentage of participants who achieved PASI 75, 90, and 100 as well as those that achieved sPGA of 0 (clear) or 1 (almost clear). For the Canadian study, the researchers also looked at the treatment impact on the dermatology life quality index (DLQI) and psoriasis symptom inventory (PSI).

In the combined study analysis, almost 75% of participants achieved PASI 75 and 52.2% of patients achieved PASI 90. Participants in the Canada study tended to do better than their US counterparts, with 75.5% and 53.7% achieving PASI 75 and 90, respectively, compared with 66.7% and 43.6%, achieving PASI 75 and 90, respectively, in the US. Participants in the Canada study also fared better in achieving sPGA of 0/1, with 70.4% of patients achieving such vs 69.0% in the US.

Kim et al further examined response based on prior medication in the Canada study. Among those who were previously prescribed anti–IL-17 biologics (N=, nearly half (49.0%) achieved PASI 90 and 35.7% achieved PASI 100. Patients with inadequate response to anti–IL-23 biologics (N=45) did even better on brodalumab, with 64.4% achieving PASI 90 and 44.4% achieving PASI 100. Of the patients who had inadequate response on anti–TNF- α ­ (N= 38) 55.3% and 47.4% achieved PASI 90 and PASI 100, respectively. Finally, 51.4% and 40% of patients who had previously attempted anti–IL-12/23 (N=35) achieved PASI 90 and PASI 100, respectively.

The safety outcomes were similar to brodalumab’s established safety profile. More patients in the Canada reported at least 1 treatment emergent adverse events than those in the US study (64.9% vs 15.4%). Arthralgia (8.0%), headache (6.4%), psoriasis (6.4%), and fatigue (5.2%) were among the most common events reported in the Canadian study. In the US study, prediabetes, corneal ulcer, allergic sinusitis, tooth abscess, sciatica, and folliculitis were reported, with each being noted by 1 individual. None of the US adverse events were considered serious or related to brodalumab itself. In terms of psychiatric events, there were no reports of suicide or suicidal ideation.

In the Canadian study, Papp and colleagues also assessed brodalumab’s impact on patients’ quality of life. They find 67.6% reduction in DLQI scores from baseline to week 16 (95% CI: -73.5%, -61.7%; n=212) and 64.4% reduction in the PSI scores (95% CI: -70.5%, -58.3%; n=216).

Brodalumab was originally approved in 2017 by the US Food and Drug Administration for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and have failed or have stopped responding to them. A novel human monoclonal antibody that binds to the IL-17 receptor, brodalumab is considered to have a broad mechanism of action inhibiting multiple proinflammatory cytokines involved in psoriasis. Because of observed suicidal ideation and behavior, there is a Risk Evaluation and Mitigation Strategy in place to mitigate risk.²

“Brodalumab, which blocks the interleukin (IL)–17 receptor A for multiple inflammatory cytokines, was effective and well tolerated in patients with moderate-to-severe psoriasis and inadequate response to prior biologics, including those targeting IL-17A,” Papp and colleagues concluded.

Papp et al acknowledged the research was supported by Ortho Dermatologics Medica.

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References

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

2. FDA approves new psoriasis drug. News release. February 15, 2017. Accessed June 5, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-psoriasis-drug