Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening inflammatory skin disease characterized by widespread pustules, with interleukin-36 signaling playing a key role in its pathogenesis. The phase 2 trial evaluated the efficacy and safety of spesolimab, an anti-interleukin-36 receptor monoclonal antibody, for treating GPP flares. In this trial, 53 patients experiencing a GPP flare were randomized in a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab or placebo. The primary endpoint was a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at the end of week 1, while the key secondary endpoint was a GPPGA total score of 0 or 1 at the same time point.

The results showed that 54% of patients in the spesolimab group achieved a pustulation subscore of 0 compared to 6% in the placebo group, and 43% achieved a total score of 0 or 1 compared to 11% in the placebo group. However, spesolimab was associated with infections and systemic drug reactions. Infections occurred in 17% of patients during the first week and in 47% by week 12. Antidrug antibodies were detected in 46% of patients who received spesolimab. The study concluded that spesolimab led to higher lesion clearance than placebo but was associated with notable side effects, indicating the need for longer and larger trials to better understand its effects and risks.

Reference: Bachelez H, Choon SE, Marrakchi S, et al. Trial of Spesolimab for Generalized Pustular Psoriasis. N Engl J Med. 2021;385(26):2431-2440. doi: 10.1056/NEJMoa2111563.