Most Patients With GPP Failed to Achieve Clear Skin on Small-Molecule Therapy

Many patients entering EFFISAYIL®2 failed to reach complete skin clearance after treatment with traditional small-molecule therapy for generalized pustular psoriasis (GPP).1 Results of this analysis were presented at the 2025 SDPA Annual Summer Dermatology Conference in Washington, DC, from June 25 to June 29th.

Led by Arash Mostaghimi, MD, MPH, FAAD, vice chair of clinical trials and innovation at Brigham and Women’s Hospital and associate professor at Harvard Medical School, investigators aimed to determine patients’ GPP burden, measured by GPPGA and DLQI scores, before entering EFFISAYIL® 2. Scores were stratified by baseline small-molecule medication.

GPP is a potentially life-threatening inflammatory skin disease characterized by chronic symptoms and episodic flares of widespread skin postulation. On September 1, 2022, the US Food and Drug Administration (FDA) approved spesolimab (Spevigo), an anti-interleukin-36 receptor monoclonal antibody, to treat GPP in adult and pediatric patients aged ≥ 12 years weighing ≥ 40 kg2.2 Spesolimab can significantly reduce the risk of GPP flares by 84%.

Despite spesolimab on the market, many patients treat their GPP with small-molecule drugs, such as corticosteroids.3 Biological therapies offer better targeting and lower systemic adverse events than small-molecule drugs, but their high costs and invasive administration modes limit their widespread use.

EFFISAYIL®2, a phase 2b randomized, multicenter, parallel-group, double-blind, placebo-controlled phase trial, evaluated spesolimab in 121 patients aged 12 – 75 years with GPP. All patients in the study had a documented history of GPP and a GPPGA total score of 0 or 1 at screening and randomization.

Most patients (74%) were treated with a systemic small-molecule drug before randomization, such as acitretin (37%), cyclosporine (21%), MTX (12%), and 2 small molecules (4%). More than half of the participants in each group were female: acitretin (28%), cyclosporine (16%), MTX (9%), and 2 small molecules (4%). The mean age was 30 – 42 years, and the mean body mass index (BMI) was 23 – 27 kg/m2. Most participants were Asian, excluding the MTX group, which had more who identified as White.

The team measured GPP burden before randomization by the proportion of patients with a total GPPGA score of 1, and a mean DLQI score at baseline.

GPPGA assessed the burden of the skin symptoms of GPP on a scale of 0 (clear; no scaling or crusting, no visible pustules, normal or post-inflammatory hyperpigmentation) to 4 (severe scaling or crusting, deep fiery red erythema, and very-high density pustules with pustular lakes). DLQI, with a scale of 0 (no effect on patients’ life) to 30 (extremely large effect on patients’ life), is a 10-item questionnaire reporting the impact of dermatological diseases on patients’ quality of life. The DLQI has 6 domains: symptoms and feelings, work and school, personal relationships, treatment, leisure, and daily activities.

Most patients at baseline did not have clear skin after taking a small-molecule drug for GPP. The proportion of patients with a baseline GPPGA total score of 1 was 95.6% in the acitretin group, 84% in the cyclosporine group, 66.7% in the MTX group, 80% in the 2 small molecules group, and 87.1% in the no medication group.

All groups had a mean baseline DLQI score of > 5, suggesting the small-molecule drug had a moderate effect on quality of life. The mean DLQI scores were 8.3 for acitretin, 7.7 for cyclosporine, 9.9 for MTX, 5.4 for 2 small molecules, and 8.6 for no medication.

“These findings suggest that patients would benefit from approved, targeted GPP therapy to reduce the clinical burden of GPP,” investigators concluded.

References

1. Mostaghimi A, Merola J, Gottlieb A, et al. Generalized pustular psoriasis (GPP) control is limited on traditional small-molecule therapy as measured by the GPPGA and DLQI: Baseline data from the EFFISAYIL® 2 trial.” Presented at the 2025 SDPA in Washington, DC, from June 25 – June 29th.

2. Stewart, J. Spevigo FDA Approval History. Drugs.com. March 20, 2024. https://www.drugs.com/history/spevigo.html. Accessed July 9, 2025.

3. Li Y, Cheng Y, Cai Y, et al. Novel Small-Molecule Treatment and Emerging Biological Therapy for Psoriasis. Biomedicines. 2025;13(4):781. Published 2025 Mar 23. doi:10.3390/biomedicines13040781