In a placebo-controlled study of 123 patients with generalized pustular psoriasis (GPP) flares, the anti-interleukin-36 receptor monoclonal antibody spesolimab significantly reduced the risk of a GPP flare and flare occurrence when administered in high doses over 48 weeks. “Given the chronic nature of GPP, a treatment for flare prevention is a significant shift in the clinical approach, and could ultimately lead to improvements in patient morbidity and quality of life,” the authors conclude.
At 60 hospitals and clinics in 20 countries, the phase 2b trial included adolescents and adults aged 12 to 75 years with at least 2 past GPP flares and a GPP Physician Global Assessment (GPPGA) score of 0 or 1 at screening and random assignment. GPP history was evaluated using the European Rare and Severe Psoriasis Expert Network criteria. Randomization to subcutaneous placebo or low-, medium-, or high-dose spesolimab over 48 weeks was assessed based on the primary endpoint of time to first GPP flare.
“All patients were either Asian (79 [64%] of 123) or White (44 [36%]),” the researchers report. “Patient groups were similar in sex distribution (76 [62%] female and 47 [38%] male), age (mean 40.4 years, SD 15.8), and GPP Physician Global Assessment score. A non-flat dose-response relationship was established on the primary endpoint. By week 48, 35 patients had GPP flares; seven (23%) of 31 patients in the low-dose spesolimab group, nine (29%) of 31 patients in the medium-dose spesolimab group, three (10%) of 30 patients in the high-dose spesolimab group, and 16 (52%) of 31 patients in the placebo group. High-dose spesolimab was significantly superior versus placebo on the primary outcome of time to GPP flare (hazard ratio [HR] = 0.16, 95% CI 0.05–0.54; P = 0.0005) endpoint. HRs were 0.35 (95% CI 0.14–0.86, nominal P = 0.0057) in the low-dose spesolimab group and 0.47 (0.21–1.06, P = 0.027) in the medium-dose spesolimab group. We established a non-flat dose-response relationship for spesolimab compared with placebo, with statistically significant p values for each predefined model (linear P = 0.0022, emax1 P = 0.0024, emax2 P = 0.0023, and exponential P = 0.0034). Infection rates were similar across treatment arms; there were no deaths and no hypersensitivity reactions leading to discontinuation.”