Spesolimab curbs flares in generalized pustular psoriasis

The anti-interleukin (IL)-36 receptor monoclonal antibody spesolimab not only helps treat generalized pustular psoriasis (GPP) flares but also prevent them, according to the results of the Effisayil 2 study presented at WCD 2023.

“High-dose spesolimab was superior to placebo in preventing flares, with an 84-percent reduction in the risk of flare development over 48 weeks (hazard ratio [HR], 0.16, 95 percent confidence interval, 0.05–0.54) and no flares after week 4,” reported one of the study authors Dr Bruce Strober of Yale University and Central Connecticut Dermatology, Connecticut, US.

“This translated into improved patient outcomes,” Strober added.

In the study, 123 patients with GPP were randomly assigned to receive treatment with placebo (n=31) or a low-dose (300 mg loading dose [LD], then 150 mg subcutaneously every 12 weeks; n=31), medium-dose (600 mg LD, then 300 mg subcutaneously every 12 weeks; n=31), or high-dose (600 mg LD, then 300 mg subcutaneously every 4 weeks; n=30) spesolimab regimen over 48 weeks.

Strober and colleagues noted a nonflat dose-response relationship for the primary endpoint of time-to-first GPP flare by week 48.

“From a hierarchical testing perspective, high-dose spesolimab demonstrated statistically significant improvement over placebo on the primary endpoint (HR, 0.157, 95 percent CI, 0.05–0.54; p=0.0005) and the key secondary endpoint of the occurrence of ≥1 GPP flare (risk difference, −0.39, 95 percent CI, −0.62 to −0.16; p=0.0013) by week 48,” according to Strober.

For other endpoints, high-dose spesolimab reduced the risks of disease worsening (assessed using Psoriasis Symptom Scale [PSS] score; HR, 0.42, 95 percent CI, 0.20–0.91; p=0.0134) and health-related quality of life decline (based on Dermatology Life Quality Index [DLQI] score; HR, 0.26, 95 percent CI, 0.11–0.62; p=0.0010) up to 48 weeks.

“No new safety signals were identified [with spesolimab],” Strober noted, adding that the safety profile of the drug was favourable.

The frequency of adverse events (AEs) was similar across all treatment groups and did not follow a dose-dependent trend. Skin disorders and infections were the most common AEs.

A higher rate of localized injection site reactions was observed among spesolimab-treated patients, but Strober pointed out that such events were mostly mild and did not lead to treatment discontinuation. There were no cases of AEs that resulted in death.

“IL-36 signalling plays a key role in the pathogenesis of GPP, promoting neutrophil infiltration and the formation of pustules,” Strober said. [Br J Dermatol 2021;185:660-662; Am J Clin Dermatol 2022;23:13-19]

In the earlier Effisayil 1 study, treatment with intravenous spesolimab led to rapid pustular clearance and effectively controlled acute flares in patients with GPP, which led to the drug’s approval in several countries. [N Engl J Med 2021;385:2431-2440]

Now, the Effisayil 2 data have shown the positive benefit-risk profile of spesolimab over 48 weeks, supporting a role for the drug as a therapy for GPP flare prevention, Strober said.