Generalized Pustular Psoriasis Flare Symptoms Quickly Treated With Spesolimab

While clinically meaningful improvements can be achieved in the majority of patients with a single dose, an optional second dose may be needed.

Spesolimab, an anti-interleukin (IL)-36 receptor antibody, rapidly controls symptoms of flare among patients with generalized pustular psoriasis (GPP). These study findings were published in Journal of the American Academy of Dermatology.

Researchers conducted a global, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effects of spesolimab on GPP flare. Participants (N=53) were randomly assigned in a 2:1 ratio to receive a single intravenous dose of spesolimab 900 mg (n=35) or placebo (n=18).

An optional, second open-label spesolimab dose was administered on day 8 among any patient with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of at least 2 points and pustulation subscore of at least 2 points or after day 8 for a new flare event. At week 12, patients could enroll in a 5-year open-label extension. Efficacy through week 12 was evaluated in this analysis.

Participants who received spesolimab had a median age of 41.0 (range, 21-69) years, 60.0% were women, 100% had a GPPGA total score of 3 to 4 points at baseline, 82.9% had a GPPGA pustulation score between 3 and 4 points, and 27.6% were positive for an interleukin 36 receptor antagonist (IL36RN) mutation.

[T]hese data indicate that spesolimab rapidly blocks the action of the IL-36 signaling pathway, which plays a central role in pathogenesis of GPP, and maintains this effect over time…

A GPPGA pustulation subscore of 0 points was achieved by day 2 among 11.4% of participants, by day 3 among 31.4% of participants, and by week 1 among 54.3% of participants.

Overall, 23 participants received 1 dose, 12 received the optional second dose at day 6, 8 experienced a new flare, and 15 received additional treatments.

The proportion of participants who achieved a GPPGA pustulation subscore of 0 points at week 12 was 65.2% among single-dose recipients and 50.0% among 2-dose recipients. Few patients (22.2%) randomized to receive placebo met efficacy endpoints.

Baseline demographic and disease characteristics did not predict how many doses of spesolimab participants received. However, more patients who received 1 dose had an IL36RN mutation (30.4% vs 8.3%) compared with the 2-dose group, respectively. Among the 2-dose recipients, the presence of the IL36RN mutation did not predict response.

Similarly, no predictors for response to spesolimab were identified among the entire cohort.

Limitations of the study include the small sample size and the lack of a safety analysis.

Study authors conclude, “[T]hese data indicate that spesolimab rapidly blocks the action of the IL-36 signaling pathway, which plays a central role in pathogenesis of GPP, and maintains this effect over time, further supporting its use as a therapeutic option for patients with a GPP flare.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Elewski B, Lebwohl MG, Anadkat MJ, et al. Rapid and sustained improvements in GPPGA scores with spesolimab for treatment of generalized pustular psoriasis flares in the randomized, placebo-controlled Effisayil 1 study. J Am Acad Dermatol. 2023;S0190-9622(23)00350-X. doi:10.1016/j.jaad.2023.02.040