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

TRADE NAME

• • Spevigo

MECHANISM OF ACTION 

• • 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.

FDA-APPROVED FOR³ 

• • 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 

OFF-LABEL DERMATOLOGIC USES

• • Pyoderma gangrenosum^4,5
  • Acrodermatitis continua of Hallopeau⁶

DOSING³

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

ADMINISTRATION CONSIDERATIONS³

• • 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.

SIDE EFFECTS

• • 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 

DRUG INTERACTIONS

• • Live vaccines should be avoided.³

CONTRAINDICATIONS 

• • History of anaphylaxis or hypersensitivity to spesolimab³ 

PREGNANCY AND BREASTFEEDING

• • 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.

MONITORING

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

REFERENCES 

1. 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 https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761244s003lbl.pdf. 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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