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IL-36 Receptor Antagonist Pregnancy: Avoid — limited data; potential immunosuppressive effect on fetus; effective contraception during and for 5 months after treatment

Spesolimab

Brand names: Spevigo

Adult dose

Dose: Acute flare: 900 mg IV single dose (may give second 900 mg dose after 1 week if inadequate response); Prevention: 600 mg SC every 12 weeks
Route: Intravenous (acute) / Subcutaneous (maintenance)
Frequency: Single IV dose for acute flare; SC every 12 weeks for prevention
Max: 900 mg per IV dose
Generalized pustular psoriasis (GPP) — rare, life-threatening; only treatment with specific GPP indication in UK; acts within hours of infusion

Paediatric dose

Dose: Not established N/A/kg
Route: N/A
Frequency: N/A
Max: N/A
Not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Not licensed in paediatrics

Clinical pearls

  • Effisayil-1 trial (Bachelez et al. NEJM 2021): spesolimab achieved pustular clearance or near-clearance (GPPGA pustulation subscore 0 or 1) in 54% vs 6% placebo at week 1 — remarkable speed of response in GPP, a historically difficult-to-treat condition
  • Generalized pustular psoriasis (GPP) pathogenesis: IL-36 cytokine pathway is central — IL36RN (IL-36 receptor antagonist) mutations impair negative feedback, leading to uncontrolled IL-36 signalling, neutrophil recruitment and explosive sterile pustulosis; spesolimab blocks the IL-36 receptor
  • MHRA 2022 approved; first and only treatment specifically licensed for GPP flares in Europe; speed of response (pustule clearance within 24-48 hours) transforms management of GPP which previously relied on ciclosporin, acitretin, or infliximab off-label
  • DRESS reactions reported — monitor for rash with systemic features (fever, lymphadenopathy, organ involvement); hold spesolimab and manage with systemic steroids if DRESS suspected
  • Effisayil-2 (prevention, NEJM 2024): SC spesolimab every 12 weeks significantly reduced GPP flares vs placebo — maintenance indication now also available; GP involvement in monitoring between hospital episodes important

Contraindications

  • Active serious infections
  • Known hypersensitivity

Side effects

  • Infections (urinary tract, upper respiratory)
  • Drug reaction with eosinophilia and systemic symptoms (DRESS — rare but reported)
  • Pruritus
  • Nausea
  • Arthralgia

Interactions

  • Live vaccines — avoid
  • CYP450 substrates — limited data on normalisation of CYP450 with IL-36 pathway inhibition

Monitoring

  • Clinical response (pustule clearance within 1 week)
  • Signs of infection
  • DRESS monitoring (rash, fever, LFTs, FBC with eosinophils)
  • Skin assessment at each maintenance dose

Reference: BNFc; BNF 90; Effisayil-1 trial (Bachelez et al. NEJM 2021); Effisayil-2 (NEJM 2024); MHRA SPC Spevigo 2022; BAD Generalized Pustular Psoriasis Guideline (2023). Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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