Arthur David Burden, MD, FRCP

Credit: psoriasiscouncil.org

Spesolimab is both safe and effective in treating patients with generalized pustular psoriasis (GPP) flares regardless of demographics and baseline clinical characteristics, according to recent findings.¹

The anti-interleukin (IL)-36 receptor monoclonal antibody has been approved for GPP flares in adults in the US, Europe, and elsewhere.^{2, 3} Effisayil 1 was a prior study of single-dose spesolimab in 53 participants with GPP flares, and its results showed rapid skin and pustular clearance in 1 week of treatment.⁴

The new subgroup analysis of the Effisayil 1 study, authored by Arthur David Burden, MD, FRCP, from the School of Infection and Immunity at the University of Glasgow, was designed to assess the effectiveness in different subpopulations.

“The present pre-specified subgroup analysis from Effisayil 1 provides insight into the actions of spesolimab according to patient demographics and clinical characteristics at baseline,” Burden and colleagues wrote.

Study Background

The Effisayil 1 study had involved 53 patients with a GPP flare and it was a multicenter, double-blind, randomized, placebo-controlled study. Patients were given a single dose of spesolimab (900 mg intravenously) or a placebo.

The study found that patients receiving spesolimab had a faster clearance of pustular and skin symptoms compared to those receiving the placebo. Specifically, 54.3% of those given spesolimab achieved a primary endpoint of a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) pustulation subscore of 0, compared to 5.6% of those in the placebo arm.

Additionally, 42.9% patients receiving spesolimab achieved a key secondary endpoint of a GPPGA total score of 0 or 1, compared to 11.1% of participants given placebo. At week 1, more patients receiving spesolimab experienced adverse events compared to those receiving the placebo, with 65.7% compared to 55.6% patients experiencing AEs, respectively.

Subgroup Analysis and Findings

The investigators in the subgroup analysis evaluated the safety and effectiveness of a single-dose of spesolimab (900 mg IV) compared to placebo in new, pre-specified subgroups of study participants, with each subgroup consisting of a minimum of 5 patients in at least 2 categories.

These subgroups included such variables as the following: sex, plaque psoriasis presence, background medication for GPP prior to randomization, race, body mass index (BMI), GPPGA total score, IL36RN mutation status, GPPGA pustulation subscore, GPPASI total score, and Japanese Dermatological Association (JDA) GPP severity index.

The investigators noted that their primary endpoint was the achievement of a GPPGA pustulation subscore of 0 at Week 1, while their study’s key secondary endpoint was a GPPGA total score of 0 or 1 at Week 1. The team defined non-response for the analysis of these endpoints as missing values or any use of other medication for GPP within the first week of the Effisayil 1 trial.

Overall, the research team reported that the placebo arm had a higher percentage of female and Asian patients compared to the spesolimab arm, but they added that clinical characteristics were generally well-balanced across the subgroups in both arms, with comparable background medications used for GPP prior to randomization.

At Week 1, they noted that spesolimab demonstrated a greater efficacy in achieving a GPPGA pustulation subscore of 0 and a GPPGA total score of 0 or 1 compared to the placebo group. The investigators added that the efficacy of spesolimab was consistent across all the patient subgroups analyzed for the primary and key secondary endpoints.

The team also reported that most risk differences fell within the overall 95% confidence interval. However, they added that there were some subgroups with small group sizes that limited statistical analysis, such as patients with severe JDA GPP severity index at baseline or those with IL36RN mutations.

“In conclusion, spesolimab is efficacious and has a consistent and favorable safety profile in patients presenting with a GPP flare, regardless of baseline sex, race, BMI, GPPGA total score, GPPGA pustulation subscore, GPPASI total score, JDA GPP severity index, presence of plaque psoriasis at baseline, background medication be- fore randomization and IL36RN mutation status,” they wrote.

References

1. ^{Burden AD, Okubo Y, Zheng M, Thaçi D, van de Kerkhof P, Hu N, Quaresma M, Thoma C, Choon SE. Efficacy of spesolimab for the treatment of generalized pustular psoriasis flares across pre-specified patient subgroups in the Effisayil 1 study. Exp Dermatol. 2023 May 4. doi: 10.1111/exd.14824. Epub ahead of print. PMID: 37140190.}
2. ^{FDA U. Spesolimab Prescribing Information. FDA. 2022. Accessed 28 October 2022. https://www.accessdata.fda.gov/drugsatfda_ docs/label/2022/761244s000lbl.pdf. Published 2022.}
3. ^{Boehringer-Ingelheim. European Commission approves SPEVIGO® (spesolimab) for generalized pustular psoriasis flares. 2022. Accessed 22 December 2022. https://www.boehringer-ingelheim. com/human-health/skin-diseases/gpp/european-commission -approves-spevigo-spesolimab-generalized. Published 2022.}
4. ^{Bachelez H, Choon SE, Marrakchi S, et al. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021;385(26):2431-2440.}