Brodalumab and Low Immunogenicity in Moderate to Severe Plaque Psoriasis

In patients with moderate to severe psoriasis, treatment with brodalumab is associated with low immunogenicity and high efficacy recapture rates, according to an analysis published in the Journal of the American Academy of Dermatology.

The study pooled data from a 12-week phase 2 study (ClinicalTrials identifier: NCT00975637), the open-label extension (ClinicalTrials identifier: NCT01101100), and 3 phase 3 trials (ClinicalTrials identifiers: NCT01708590/NCT01708603/NCT01708629). Trials featured treatment with brodalumab at 70, 140, or 210 mg every 2 weeks. Patients enrolled in the studies had moderate to severe plaque psoriasis. The researchers in each trial assessed skin clearance efficacy of the drug according to improvements of ≥75% from baseline in the Psoriasis Area and Severity Index (PASI 75) score and changes in the static physician’s global assessment score.

Antidrug antibodies (ADAs) were found in approximately 2.7% of patients who received brodalumab. Only 1.4% of patients had ADAs that were transient, with 0 neutralizing ADAs. Among ADA-positive patients who received 210 mg brodalumab every 2 weeks, 60.0% achieved a static physician’s global assessment score of 0 or 1 at 12-week follow-up. This was in comparison to 79.1% of ADA-negative patients who achieved a similar score at 12 weeks.

A PASI 75 score was reported in 100% of patients who experienced disease return and were subsequently retreated with 210 mg brodalumab every 2 weeks. Brodalumab was associated with fewer hypersensitivity reactions compared with placebo. In the trial that compared brodalumab with ustekinumab, treatment with brodalumab was associated with a lower rate of injection-site reactions (1.8% vs 2%, respectively).

A limitation of the analysis was the inclusion of only 1 study that assessed retreatment in the enrolled cohort of patients with psoriasis.

“Brodalumab compares favorably with other biologics used to treat psoriasis, including those targeting tumor necrosis factor and [interleukin 17A], in terms of immunogenicity and efficacy recapture rates upon retreatment,” the researchers concluded.

The study was funded in part by Ortho Dermatologics, and the authors report conflicts of interest with AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, LEO Pharma, MedImmune/AstraZeneca, and Novartis.

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Reference

Bagel J, Lebwohl M, Israel RJ, Jacobson A. Immunogenicity and skin clearance recapture in clinical studies of brodalumab [published online June 5, 2019]. J Am Acad Dermatol. doi:10.1016/j.jaad.2019.05.094