Subcutaneous spesolimab for GPP flare prevention

High-dose, subcutaneous spesolimab was associated with fewer flares compared with placebo over 48 weeks in patients with generalised pustular psoriasis (GPP). Together with the favourable safety profile of the agent, these results support a potential role for spesolimab in the prevention of flares in patients with GPP.

“In many countries, therapy with intravenous spesolimab is an approved treatment for patients with GPP in the context of controlling acute flares,” claimed Prof. Bruce Strober (Yale University School of Medicine, CT, USA) [1]. “However, a high unmet need remains with respect to GPP flare prevention.” Therefore, the Effisayil 2 trial (NCT04399837) randomised 123 patients with GPP 1:1:1:1 to 1 of 3 doses of spesolimab or a placebo to assess the efficacy of spesolimab for the prevention of flares in GPP. The lowest dose group started with a 300 mg loading dose, followed by 150 mg every 12 weeks. The highest dose group started with a 600 mg loading dose, followed by 300 mg every 4 weeks. Prof. Strober presented the primary outcome results of time to GPP flare by week 48 [2].

High-dose spesolimab was associated with fewer GPP flares than placebo: an 84% reduction in the risk of flare development was observed, with a corresponding hazard ratio of 0.16 (95% CI 0.05–0.54; P=0.0005). In the placebo arm, 51.6% of the participants experienced at least 1 flare, compared with 12.7% of the patients in the high-dose spesolimab arm. Prof. Strober added that no flares were seen in the high-dose spesolimab group after week 4. Spesolimab also positively affected quality-of-life: high-dose spesolimab reduced the risk for Psoriasis Symptom Scale (PSS; HR 0.42; P=0.013) and Dermatology Life Quality Index (DLQI) questionnaire (HR 0.26; P=0.0010) worsening up to week 48, compared with placebo.

The authors did not observe a dose-dependent pattern with regard to safety, and the incidence of adverse events was similar between the spesolimab arms and the placebo arm. Although there was a higher rate of localised injection site reactions in the active drug arms, these events were mostly mild and did not lead to treatment discontinuation.

“The positive benefit-risk profile of subcutaneous spesolimab shows that this therapy may have a role in the prevention of flares in patients with GPP,” concluded Prof. Strober.

1. Bachelez H, et al. N Engl J Med 2021;385:2431–2440.
2. Lebwohl M, et al. Spesolimab for the prevention of generalized pustular psoriasis (GPP) flares: results from the randomized, placebo-controlled trial Effisayil 2. Late-breaker Session 1, WCD 2023, 3–8 July, Singapore, Singapore.