Treatment with the interleukin-36 inhibitor spesolimab was associated with improved lesion clearance vs placebo after one week, but also a greater incidence of infection and systemic drug reactions.
Treatment of the rare, life-threatening, inflammatory skin disease generalized pustular psoriasis (GPP) with the interleukin (IL)-36 inhibitor spesolimab was associated with improved lesion clearance, but also a greater incidence of infection and systemic drug reactions. Study findings were published in The New England Journal of Medicine.
Characterized by widespread eruption of sterile pustules, GPP-related mortality rates range from 2% to 16%, in which deaths have been attributed to septic shock and cardiorespiratory failure. Prior research indicated that patients have no standardized treatments for the condition and are at increased risk for continued health care utilization over time.
However, researchers noted emerging evidence showing that IL-36 signaling is involved in the pathogenesis of GPP. Findings of an open-label phase 1 study further showed clinical improvements in patients with GPP treated with spesolimab, a humanized anti–IL-36 receptor monoclonal antibody.
With only 7 patients involved in the analysis, they conducted a phase 2 randomized trial (Effisayil 1) to examine the efficacy and safety of spesolimab, compared with placebo, in patients presenting with a GPP flare. In the phase 2 trial, patients with a GPP flare were randomly assigned at a 2:1 ratio to receive a single 900-mg intravenous dose of spesolimab (n = 35) or placebo (n = 18).
“Patients in both groups could receive an open-label dose of spesolimab on day 8, an open-label dose of spesolimab as a rescue medication after day 8, or both and were followed to week 12,” explained the study authors.
Primary outcomes assessed in the analysis was the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0 at the end of week 1 (range, 0 [no visible pustules] to 4 [severe pustulation]), with key secondary outcomes including a GPPGA total score of 0 or 1 (clear or almost clear skin) at the end of week 1.
At baseline, 46% of participants in the spesolimab group and 39% of those in the placebo group exhibited a GPPGA pustulation subscore of 3, with a further 37% and 33% showing a pustulation subscore of 4, respectively.
After treatment at the end of week 1, 19 of the 35 patients (54%) treated with spesolimab group had a reported GPPGA pustulation subscore of 0, compared with 1 of 18 patients (6%) in the placebo group (difference, 49 percentage points; 95% CI, 21-67; P < .001).
Furthermore, 15 of the 35 patients (43%) in the spesolimab group had a GPPGA total score of 0 or 1, compared with 2 of 18 patients (11%) in the placebo group (difference, 32 percentage points; 95% CI, 2-53; P = .02).
Regarding safety in the spesolimab group, drug reactions were reported in 2 patients and infections occurred in 6 of 35 (17%) vs 6% of those in the placebo group through the first week. For patients who received spesolimab at any time in the trial, infections occurred in 24 of 51 (47%) at week 12, and anti-drug antibodies were detected in 23 of 50 patients (46%) who received at least one dose of the IL-36 inhibitor.
Serious adverse events were reported in 6% of the patients who received spesolimab and in none of the patients who received placebo in the first week.
“Longer and larger trials are warranted to determine the effect and safety of spesolimab in patients with pustular psoriasis,” concluded researchers.
Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. Published online December 23, 2021. doi:10.1056/NEJMoa2111563