A recent study published in Dove Medical Press highlights the successful treatment of pediatric generalized pustular psoriasis (GPP) with spesolimab, offering a promising therapeutic option for young patients with this rare and severe inflammatory skin disease. The study, conducted at Beijing Children’s Hospital, involved five children aged 4–12 years diagnosed with GPP, who were treated with a single intravenous dose of spesolimab. The findings indicate rapid and significant improvements in disease symptoms and inflammatory markers.
GPP is characterized by widespread pustules on edematous erythema, often accompanied by fever and systemic symptoms. Current treatments for GPP in children are limited, with most options being off-label. Spesolimab, a humanized monoclonal antibody that inhibits the IL-36 receptor, has been approved for treating GPP in adults, but data on its use in children under 12 years has been scarce.
Study Design and Methods
The study enrolled five patients meeting the GPP criteria of the Japanese Dermatological Association (JDA), with a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) score ≥3, GPPGA pustulation subscore ≥2, body surface area (BSA) ≥10%, and Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score ≥10. All patients had progressing disease severity and had not achieved long-term remission on previous treatments, including adalimumab, secukinumab, acitretin, and topical drugs.
A single intravenous dose of spesolimab was administered based on body weight (450mg for 20–50kg and 900mg for ≥50kg). GPP severity was assessed using BSA, GPPGA total score, GPPGA pustulation sub-score, GPPASI, and JDA severity index for GPP. Cytokine and chemokine levels were measured before treatment and one week after spesolimab administration.
Rapid Clinical Improvement
The results showed that no new skin lesions developed after a median of 3 days post-treatment. Body temperature decreased to ≤38°C after a median of 2 days and normalized after a median of 4 days. By the end of one week, BSA, GPPGA scores, GPPGA pustulation subscores, and JDA scores significantly decreased (P = 0.008, P = 0.003, P = 0.034, P = 0.038, and P = 0.001, respectively). All patients achieved a GPPGA total score of 0/1, with a median of 3 days, and a GPPGA pustulation subscore of 0 after a median of 4 days. The median time to achieve a GPPASI 75 response was 6 days.
Reduction in Inflammatory Markers
Significant reductions in white blood cell (WBC) and C-reactive protein (CRP) levels were observed seven days after spesolimab administration (P = 0.029 and P = 0.001, respectively), while albumin levels significantly increased (P = 0.018). Furthermore, levels of IL-36α, IL-36β, and IL-36γ decreased post-treatment, with significant reductions in IL-36α (P = 0.023) and IL-36β (P = 0.043). Levels of IL-17A, IL-17C, and IL-6 also decreased significantly (P = 0.004, P = 0.001, and P = 0.001, respectively).
Safety and Tolerability
Spesolimab was well-tolerated in all five patients. One patient experienced an upper respiratory infection in the first week following treatment, which resolved with antibiotics. No other adverse events were reported during the 2 to 8-month follow-up period.
Clinical Implications
The study's findings suggest that spesolimab is a safe and effective treatment for pediatric GPP. "Our study is the first spesolimab-treatment report involving GPP patients under 12 years," the authors noted. "All our five participants had a GPPGA pustulation subscore of 0 and GPPGA0/1 at week 1. In contrast to findings from the RCTs and real-world studies, spesolimab might result in better clearance of lesions in children."
The researchers also highlighted the importance of IL-36 cytokines in the pathogenesis of GPP. Spesolimab, by inhibiting the IL-36 receptor, effectively suppresses the IL-36 signaling pathway, leading to a reduction in inflammation. "Those elucidated IL-36 and related inflammatory storm could decrease through inhibiting IL-36Rs," the authors explained.
While the study provides valuable insights, the authors acknowledge limitations such as the small sample size, absence of control groups, and short follow-up period. They emphasize the need for high evidence-level trials to confirm these findings and further evaluate the long-term efficacy and safety of spesolimab in pediatric GPP patients.
This study marks a significant step forward in the treatment of pediatric GPP, offering hope for improved outcomes and quality of life for affected children.
