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 signalling, 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 favourable safety profile

NICE states (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

References:

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.