Intravenous spesolimab for (re)treatment of generalized pustular psoriasis flares in patients receiving subcutaneous spesolimab: Results from the 5-year, open-label, EFFISAYIL ON extension study

Introduction: Spesolimab is an anti-interleukin-36 monoclonal antibody approved for the treatment of generalized pustular psoriasis (GPP). We report on (re)treatment of GPP flares with intravenous (IV) spesolimab in patients receiving long-term subcutaneous (SC) spesolimab in EFFISAYIL ON. The objectives were to (1) investigate long-term efficacy of SC spesolimab for flare prevention in the EFFISAYIL ON study, in which over 100 patients with GPP have received SC spesolimab for up to 5 years and (2) describe the efficacy and safety of IV spesolimab in patients with a high burden of GPP, who have experienced a flare while receiving long-term SC spesolimab in EFFISAYIL ON. Methods: EFFISAYIL ON (NCT03886246) is an ongoing 5-year extension of the EFFISAYIL 1 and EFFISAYIL 2 trials. Patients received SC spesolimab (300 mg every 4, 6, or 12 weeks; dose escalation and de-escalation for flare recurrence/resolution allowed per protocol) for up to 252 weeks. In case of a protocol-defined GPP flare, patients received IV spesolimab 900 mg (≤2 doses within 1 week). Results: Of 131 patients enrolled from the parent trials, 21 (16.0%) received IV spesolimab to treat a total of 36 flare events (single dose, n=29; double dose, n=7). IV spesolimab demonstrated rapid control of flares: GPP Physician Global Assessment (GPPGA) pustulation subscore of 0 in 50.0% (n=18) of flare treatments at Week 1 and 58.3% (n=21) at Week 2; GPPGA total score of 0/1 in 41.7% (n=15) at Week 1 and 55.6% (n=20) at Week 2. Safety data were consistent with the known safety profile of spesolimab. Conclusion: Sustained efficacy was observed in most patients treated with SC spesolimab for GPP flare prevention; for those who did experience flares, preliminary results from EFFISAYIL ON demonstrate that IV spesolimab is an effective and well-tolerated treatment. These findings support the complementary roles of IV and SC spesolimab in the long-term management of GPP.