Pustular Psoriasis Relief: Spesolimab Cuts Flares and Boosts Quality of Life in GPP

Generalized pustular psoriasis (GPP) is a rare, life-threatening inflammatory skin disease characterized by recurrent flares of sterile pustules and systemic symptoms. The EFFISAYIL 2 trial, a 48-week, multicenter, randomized, double-blind, placebo-controlled Phase IIb study, evaluated the efficacy of spesolimab, a humanized monoclonal antibody targeting the interleukin-36 receptor (IL-36R), in preventing GPP flares and improving patient quality of life (QOL).

In the trial, patients with a history of at least two GPP flares in the previous year were randomly assigned to receive various dosing regimens of spesolimab or placebo. The regimen of a 600 mg subcutaneous (SC) loading dose (LD) followed by 300 mg SC every four weeks (q4w) significantly reduced the risk for GPP flares compared with placebo. This dosing regimen was the only one among those tested to achieve a statistically significant reduction in flare occurrence over the 48-week period.

A post hoc analysis focused on the subset of patients receiving the efficacious dosing regimen (600 mg SC LD; 300 mg SC q4w) revealed that nearly two-thirds (63.3%) achieved sustained improvement in skin symptoms, defined as a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 0 or 1 at all visits up to week 48, without the need for additional medications. In addition, by week 4, a significantly greater proportion of patients treated with spesolimab achieved improvement in the GPPGA pustulation subscore compared to those receiving placebo (63.6% vs 25.8%).

This improvement was consistent even under more stringent criteria, including subscores for pustulation, scaling, and erythema. The most pronounced effect was observed in the pustulation subscore, with improvements evident as early as week 4.

QOL, which was assessed using the Dermatology Life Quality Index (DLQI), also improved significantly in the spesolimab group. A greater percentage of patients treated with spesolimab achieved sustained quality of life improvement: 24.1% maintained a DLQI score of 0 or 1 at all visits through week 48, compared to just 3.2% in the placebo group. Between baseline and week 48, 50%-80% of patients on spesolimab consistently experienced minimal impact to QOL (DLQI 0 or 1), compared with 0%-33% of those receiving placebo.

“The higher degree of overlap between GPPGA and DLQI improvement among patients receiving spesolimab (600 mg SC LD; 300 mg SC q4w) in this analysis compared with patients receiving placebo indicates that symptomatic benefits of treatment on the severity of pustules, erythema, and scaling translate into a positive impact on patient QOL.” the researchers wrote. “In conclusion, this analysis of the EFFISAYIL 2 trial showed that the approved dose of spesolimab (600 mg SC LD; 300 mg SC q4w) provides effective long-term treatment of GPP through sustained improvement of both symptoms and QOL burden in a substantially higher proportion of patients compared with placebo.”