Spesolimab for treating generalised pustular psoriasis flares

Spesolimab for treating generalised pustular psoriais:

• the interleukin (IL)-36 signaling pathway is recognized as the key driver of the pathogenesis of generalized pustular psoriasis (GPP)
  • GPP is the most severe form of psoriasis and is characterized by the eruption of widespread neutrophilic sterile pustules that are frequently accompanied by signs of systemic inflammation
    • exact prevalence of GPP is unknown, but, globally, can be estimated as 1-7 cases per million persons, with significant regional variability (1)
    • usually occurs in adults, although children and infants may be affected (2)
      
      
• spesolimab is a humanized monoclonal antibody against the IL-36 receptor
  • is a first-in-class humanized monoclonal antibody that binds specifically to the IL-36 receptor to antagonize IL-36 signaling, and inhibit downstream activation of proinflammatory and profibrotic pathways (2)
    
    
• spesolimab has been shown to be effective in the management of GPP, both in the rapid control of the flares and in preventing their recurrence in the long-term, while maintaining a favorable safety profile

NICE state (3):

Spesolimab is recommended as an option for treating generalised pustular psoriasis (GPP) flares in adults, only if it is used to treat:

• initial moderate to severe flares when:
  • the Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score is 3 or more (at least moderate), and
  • there are fresh pustules (new appearance or worsening of existing pustules), and
  • the GPPGA pustulation subscore is at least 2 (at least mild), and
  • at least 5% of the body's surface area is covered with erythema (abnormal redness of the skin or mucous membranes) and has pustules
• subsequent flares with a GPPGA pustulation subscore of 2 or more (at least mild), if the last flare was treated with spesolimab and resolved to a GPPGA pustulation subscore of 0 or 1 (clear or almost clear skin)
• a second dose of spesolimab can be used after 8 days if a flare has not resolved to a GPPGA pustulation subscore of 0 or 1
• take into account how skin colour could affect the GPPGA score and make any adjustments needed

Reference:

1. Bernardo D, Thaçi D, Torres T. Spesolimab for the Treatment of Generalized Pustular Psoriasis. Drugs. 2024 Jan;84(1):45-58.
2. Gwillim EC, Nichols AJ. Spesolimab for generalized pustular psoriasis: a review of two key clinical trials supporting initial US regulatory approval. Front Immunol. 2024 Jul 22;15:1359481.
3. NICE (June 18th 2025). Spesolimab for treating generalised pustular psoriasis flares