Subcutaneous Spesolimab Effective for Generalized Pustular Psoriasis Symptoms

New analyses presented at the American Academy of Dermatology (AAD) Annual Meeting in Orlando have highlighted the potential benefits of spesolimab-sbzo (Spevigo) treatment on both the physical symptoms and mental health burden related to generalized pustular psoriasis (GPP).1,2

These post hoc exploratory analysis results were announced by Boehringer Ingelheim and resulted from the EFFISAYIL 2 clinical trial, during which spesolimab’s efficacy and safety in individuals impacted by GPP.1 GPP is a serious dermatologic condition which is distinct from plaque psoriasis and is a chronic inflammatory neutrophilic disease characterized by painful skin lesions as well as systemic symptoms including pain, fatigue, or fever.

“The results from EFFISAYIL 2 provide valuable insights into the chronicity of generalized pustular psoriasis,” Tina Bhutani-Jacques, MD, study author and University of California, San Francisco clinical researcher, said in a statement. “The data are a pivotal step in advancing patient-centered care in GPP.”1

Unlike other subtypes of psoriasis, GPP is recognized by dermatologists as a separate clinical entity, with the interleukin (IL)-36 pathway maintaining a central role in the condition’s progression and in treatment responses. GPP can even be life-threatening, and there is a range of mortality rates from 2% - 16%, primarily resulting from severe complications such as sepsis and multisystem organ failure.

The unpredictable nature of GPP, as well as the variety of notable comorbidities, can substantially impact patients’ quality of life, contributing to fear and anxiety regarding flare-ups. Spesolimab is designed as a humanized, selective monoclonal antibody designed to block IL-36 receptor (IL-36R) activation, which is known to be a key immune pathway implicated in various autoinflammatory diseases such as GPP.

Spesolimab represents the first targeted therapy that is approved for individuals with GPP. The medication was investigated in the EFFISAYIL clinical program, during which the investigators looked at the largest and most diverse GPP patient population in their assessment.

EFFISAYIL 1 was a phase 2 study, during which the investigative team demonstrated that a single intravenous dose of spesolimab resulted in significant improvements in participants’ symptoms related to GPP flares.1 These results included rapid clearance of GPP-related pustules and lesions on patients’ skin, and the findings supported spesolimab’s approval as the first targeted treatment for flares of GPP in adults.

In the EFFISAYIL 2 trial, subjects who had a history of GPP were randomized to receive 1 of 3 active treatment regimens or to be placed in the placebo cohort. Those participating were asked to assessed their GPP symptoms—including redness, pruritus, redness, and burning—via the Pain Visual Analog Scale (VAS), the Psoriasis Symptom Scale (PSS), and the Dermatology Life Quality Index (DLQI).2

There is a range in PSS scores from 0 - 16. The Pain VAS maintains a score range from 0 - 100, with higher values suggesting to investigators that there are more severe symptoms. Among the 30 individuals who were given subcutaneous injections of spesolimab (300 mg every 4 weeks after a 600 mg loading dose), the team found that 56.5% were shown to have a Pain VAS score of 0 by the 48-week mark.1

The mean PSS score was also noted by the investigative team as having dipped from 5.34 at baseline to 2.96 by the 48-week mark. The team also looked at quality of life rankings among participants, implementing a 10-item DLQI questionnaire, and their findings in this area indicated a notable improvement among those treated with spesolimab.

In fact, the investigators noted the mean DLQI scores saw improvement from a baseline classification of a "very large effect on patient’s life" (11.14) to a "small effect on patient’s life" (4.57) at the 48-week mark following treatment with the medication. They also observed improvements in Pain VAS, mean PSS, and DLQI scores as early as the initial evaluation occurring at Week 4.1

There has also been an EFFISAYIL ON open-label extension study, during which an investigative team has been evaluating the drug’s long-term safety and efficacy for those who previously took part in spesolimab research.1 The clinical trial program’s findings in general may provide insights that could assist healthcare professionals in making informed decisions related to treatment for GPP.

References

1. New analyses on the potential impact of SPEVIGO® in generalized pustular psoriasis patient-reported outcomes presented at AAD 2025. Boehringer Ingelheim. March 7, 2025. https://www.boehringer-ingelheim.com/us/new-analyses-explore-impact-spevigo-gpp-aad. Date accessed: March 18, 2025.

2. Bhutani T, et al. Spesolimab improves quality of life as measured by Psoriasis Symptom Scale (PSS) and Pain Visual Analog Scale (VAS) in generalized pustular psoriasis (GPP) over time: Results from the EFFISAYIL® 2 trial. Poster presented at 2025 AAD Annual Meeting; March 2025; Orlando.