Derm Topics

Spesolimab Therapeutic Cheat Sheet

Generalized pustular psoriasis (GPP) is a rare, autoinflammatory condition, with acute, severe flares of diffuse sterile pustules and systemic symptoms that can be life-threatening. Historically, cyclosporine, methotrexate, retinoids, and biologics modulating the interleukin-17 (IL-17), IL-23, and tumor necrosis factor α pathways have been used off-label for management.1 Aberrant IL-36 signaling has been implicated in subsets of patients with GPP.2 We continue our series, Therapeutic Cheat Sheet, with a closer look at spesolimab, the only FDA-approved medication to date for treating generalized pustular psoriasis, now with new subcutaneous dosing! Because spesolimab is relatively new to market, evidence for off-label use is limited to case reports.

Spesolimab Therapeutic Cheat Sheet

Compiled by: Nagasai Adusumilli, MD, MBA | Reviewed by: Karl Saardi, MD


    • Spevigo


    • A human IgG1 monoclonal antibody, spesolimab binds to the interleukin-36 receptor (IL-36R) and inhibits IL-36 signaling, leading to decreased downstream pro-inflammatory and pro-fibrotic pathways.


    • Treating generalized pustular psoriasis (GPP) flares in ages 12 years and older, with minimum weight of 40 kg
    • Treating GPP without flaring in ages 12 years and older, with minimum weight of 40 kg 


    • Pyoderma gangrenosum4,5
    • Acrodermatitis continua of Hallopeau6


Intravenous Dosage for Acute Flare

    • Single 900 mg dose infused over 90 minutes
    • If symptoms persist, additional single 900 mg dose 1 week after initial dose

Subcutaneous Dosage for Maintenance Regimen

    • If already received IV spesolimab: 4 weeks after the last IV dose, 300 mg every 4 weeks
    • If no previous IV spesolimab: loading dose of 600 mg once, followed by 300 mg every 4 weeks


    • Sterile, low protein binding in-line filter with a pore size of 0.2 micron should be used for infusion
    • If rate of infusion is slowed, the maximum total infusion time should be 180 minutes.
    • Subcutaneous 600 mg loading dose should be administered by a healthcare professional. Subsequent 300 mg doses can be self-administered.


    • Fatigue, nausea, vomiting, headache, drug-induced hypersensitivity syndrome, and infections were the most frequently reported in clinical trials.7,8
    • Symptoms of DIHS, or drug reaction with eosinophilia and systemic symptoms (DRESS), were reported with RegiSCAR scores of 1 (no DRESS) and 3 (possible DRESS).8
    • The infections included upper respiratory tract infection, urinary tract infection, cellulitis, bacteremia, herpes dermatitis, vulvovaginal candidiasis, and otitis externa, but were overall deemed mild to moderate.8
    • Limited cases of Guillain-Barre syndrome during clinical development3 


    • Live vaccines should be avoided.3


    • History of anaphylaxis or hypersensitivity to spesolimab3 


    • Limited data of spesolimab use in pregnant or breastfeeding women. No reproductive toxicity shown in murine studies.3
    • Human IgG does cross placental barrier and is likely present in human breast milk.


    • Baseline Labs:
      • Screen for tuberculosis infection with QuantiFERON-TB Gold+
    • Periodic monitoring:
      • Annual QuantiFERON-TB Gold+


    1. Robinson A, Van Voorhees AS, Hsu S, et al. Treatment of pustular psoriasis: from the Medical Board of the National Psoriasis Foundation. J Am Acad Dermatol. 2012 Aug;67(2):279-88. PMID: 22609220.
    2. Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011 Aug 18;365(7):620-8. PMID: 21848462.
    3. Boehringer Ingelheim Pharmaceuticals, Inc. Spevigo for subcutaneous or intravenous use (prescribing information). Revised March 2024. Available at Accessed March 23, 2024.
    4. Ma L, Chen X, Guo Q, et al. Rapid response to spesolimab in a patient with severe refractory pyoderma gangrenosum. Clin Exp Dermatol. 2023 Dec 19;49(1):82-84. PMID: 37706345.
    5. Guénin SH, Khattri S, Lebwohl MG. Spesolimab use in treatment of pyoderma gangrenosum. JAAD Case Rep. 2023 Feb 4;34:18-22. PMID: 36936866.
    6. Wang Y, Zhang L, Zheng J, Li X, Chen L. Spesolimab response in a girl with acrodermatitis continua of Hallopeau. JAMA Dermatol. 2024 Feb 28. Epub ahead of print. PMID: 38416455.
    7. Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. Lancet. 2023 Oct 28;402(10412):1541-1551. PMID: 37738999.
    8. Bachelez H, Choon SE, Marrakchi S, et al; Effisayil 1 Trial Investigators. Trial of spesolimab for generalized pustular psoriasis. N Engl J Med. 2021 Dec 23;385(26):2431-2440. PMID: 34936739.

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