Effect of Spesolimab on Achieving Sustained Disease Remission in Patients with Generalized Pustular Psoriasis: Results from the Effisayil 2 Study

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Kenneth Gordon
Curdin Conrad
Mark Lebwohl
Jonathan Barker
Tsen-Fang Tsai
Joseph Merola
Curdin Conrad
Min Zheng
Na Hu
Patrick Hofmann
Christian Thoma
Kilian Eyerich


GPP, spesolimab, Effisayil 2, sustained remission


Introduction: Generalized pustular psoriasis (GPP) is a chronic, rare and potentially life-threatening disease characterized by flares of widespread skin pustulation. Sustained skin clearance is a key treatment objective. Intravenous (IV) spesolimab, an anti-interleukin-36 receptor monoclonal antibody, is approved for GPP flare treatment; however, the optimal dosing and long-term efficacy of subcutaneous (SC) spesolimab treatment in patients with GPP has not yet been reported. We report the effect of SC spesolimab on achieving sustained disease remission over 48 weeks in Effisayil 2 (NCT04399837), a trial that evaluated the efficacy and safety of SC spesolimab in preventing GPP flares.

 Methods: Patients with a history of GPP were randomized (1:1:1:1) to receive placebo (n=31), low- (n=31, 300 mg loading dose [LD]; 150 mg every 12 weeks [q12w]), medium- (n=31, 600 mg LD; 300 mg q12w) or high-dose (n=30, 600 mg LD; 300 mg every 4 weeks [q4w]) SC spesolimab over 48 weeks. Sustained remission was defined as GPP Physician Global Assessment (GPPGA) total score of 0 or 1 at all visits up to Week 48, or GPPGA total score of 0 or 1 and all GPPGA subscores ≤2 at all visits up to Week 48. Sustained pustular clearance was defined as GPPGA pustulation subscore of 0 at all visits from Week 4 to Week 48. Any use of IV spesolimab or another standard of care for GPP worsening was considered a failure of remission. Missing data were imputed by a sequential logistic regression multiple imputation method. Adjusted risk differences (RD) were calculated by the Mantel−Haenszel type-weighted average of differences.

 Results: 31 patients received placebo, and 30 patients received high-dose spesolimab. Compared to placebo, more patients had sustained remission in the high-dose arm using both GPPGA total score 0 or 1 (63.3% vs 29.0%; RD [95% CI] 0.35 [0.10–0.59]), and GPPGA total score 0 or 1 and all GPPGA subscores ≤2 (60.4% vs 29.0%; RD [95% CI] 0.32 [0.07–0.56]). Compared to placebo, more patients in the high-dose arm had sustained pustular clearance over 48 weeks (63.6% vs 25.8%; RD [95% CI] 0.38 [0.14–0.62]).

Conclusion: Overall, high-dose SC spesolimab q4w is effective for the long-term management of GPP skin symptoms.


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