Treatment with interleukin (IL)-36 receptor inhibitor spesolimab in patients with generalized pustular psoriasis (GPP) was associated with higher lesion clearance by 1 week compared with placebo, but the IL-36 receptor inhibitor was also associated with greater rates of infections and system drug reactions, according to findings from the phase 2 Effisayil 1 trial published in the New England Journal of Medicine.

The study included 53 patients with a GPP flare. Patients were randomly assigned to either a single 900-mg intravenous dose of spesolimab (n=35; mean age, 43.2±12.1 years) or placebo (n=18; mean age, 42.6±8.4 years). All patients were eligible to receive an open-label spesolimab dose on day 8, an open-label spesolimab dose as a rescue medication after day 8, or both. Patients were followed to week 12 after the open-label treatments.

Investigators assessed the rate of achievement of the GPP Physician Global Assessment (GPPGA) pustulation subscore of 0 at the end of the first week. In the GPPGA subscore, scores ranged from 0 (ie, no visible pustules) to 4 (ie, severe pustulation). A secondary endpoint was achievement of the GPPGA total score of 0 (clear skin) or 1 (almost clear skin) at the end of the first week.

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At the baseline assessment, a GPPGA pustulation subscore of 3 was observed in 46% and 39% of patients in the spesolimab and placebo groups, respectively. Additionally, approximately 37% of patients in the spesolimab and 33% in the placebo arm had a pustulation subscore of 4. Overall, 19% of patients had a GPPGA total score of 4, indicating that 1 of 5 patients had severe disease.

A significantly greater percentage of patients in the spesolimab group vs the placebo group had a pustulation subscore of 0 at the end of week 1 (54% vs 6%, respectively; difference, 49 percentage points; 95% CI, 21-67; P <.001). At the end of the first week, 43% of patients in the spesolimab arm and 11% in the placebo group had a GPPGA total score of 0 or 1 (difference, 32 percentage points; 95% CI, 2-53; P =.02).

In all, 2 patients in the spesolimab group had drug reactions, with 1 of these reactions occurring alongside a drug-induced hepatic injury. In the spesolimab-treated group, 17% of patients experienced infections during the first week of treatment. By week 12, infections occurred in 47% of patients who received spesolimab at any time during the study. The investigators detected antidrug antibodies in 46% of patients who received 1 or more spesolimab doses.

Limitations of the study included its short treatment period, the small sample size, as well as its open-label nature.

Given these limitations, the researchers concluded that “longer and larger trials are warranted to determine the effect and safety of spesolimab in patients with pustular psoriasis.”

Disclosure: This clinical trial was supported by Boehringer Ingelheim. Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the original article for a full list of disclosures.


Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasisN Engl J Med. 2021;385(26):2431-2440. doi:10.1056/NEJMoa2111563