Introduction
Spesolimab (marketed as SPEVIGO®) is a novel humanized monoclonal antibody that represents the first FDA-approved treatment specifically for generalized pustular psoriasis (GPP) flares. This interleukin-36 receptor (IL-36R) antagonist represents a significant advancement in the management of this rare, life-threatening dermatological emergency.
Mechanism of Action
Spesolimab is a selective monoclonal antibody that binds to the interleukin-36 receptor (IL-36R), inhibiting the interaction of multiple IL-36 cytokines (IL-36α, IL-36β, and IL-36γ) with their receptor. IL-36 signaling plays a pivotal role in the pathogenesis of GPP by promoting neutrophil-mediated inflammation and keratinocyte activation. By blocking IL-36R, spesolimab interrupts this pro-inflammatory cascade, reducing the characteristic pustule formation and systemic inflammation associated with GPP flares.
Indications
Spesolimab is FDA-approved for the treatment of generalized pustular psoriasis (GPP) flares in adults. The approval was based on the pivotal Effisayil™ 1 trial demonstrating rapid and significant improvement in GPP symptoms.
Dosage and Administration
Standard dosing: 900 mg administered via intravenous infusion over 90 minutes Subsequent dosing: If needed, a second 900 mg dose may be administered one week after the initial dose Preparation: Reconstitute with sterile water for injection and dilute in 250 mL of 0.9% sodium chloride injection Administration: Administer via intravenous infusion using a 0.2 micron in-line filter Special populations: No dosage adjustment recommended for renal or hepatic impairmentPharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution approximately 5.3 L Metabolism: Expected to undergo catabolic pathways typical of IgG antibodies via proteolytic degradation Elimination: Terminal half-life approximately 20-25 days Clearance: Linear clearance at therapeutic doses, approximately 0.2 L/dayContraindications
• History of serious hypersensitivity reaction to spesolimab or any of its excipients • Active serious infections (until infection resolves)
Warnings and Precautions
Infections: Increased risk of serious infections. Hold treatment for serious infections until resolved Hypersensitivity reactions: Infusion-related reactions including anaphylaxis may occur Tuberculosis: Evaluate patients for latent TB before initiating treatment Vaccinations: Avoid live vaccines during treatment Hepatic impairment: Use with caution in patients with pre-existing liver diseaseDrug Interactions
Live vaccines: Contraindicated due to potential for vaccine-related infections Other immunosuppressants: May increase risk of infections (use with caution) CYP substrates: Unlikely to affect CYP enzyme activityAdverse Effects
Most common (≥5%): Asthenia, fatigue, nausea, vomiting, headache, pruritus, infusion site reactions, urinary tract infections Serious adverse effects: Serious infections (including sepsis), hypersensitivity reactions, hepatic transaminase elevations Clinical trial data: 10% of patients discontinued due to adverse reactionsMonitoring Parameters
Baseline: Complete blood count, comprehensive metabolic panel, tuberculosis screening, hepatitis screening During treatment: Monitor for signs of infection before each infusion Periodic monitoring: Liver function tests, signs of hypersensitivity reactions Response assessment: GPP Physician Global Assessment (GPPGA) score, pustule count, skin clearance Long-term: Regular assessment for opportunistic infectionsPatient Education
• Report any signs of infection (fever, chills, cough) immediately • Inform healthcare providers about spesolimab treatment before any vaccinations • Be aware of potential infusion reactions and report any symptoms during or after infusion • Understand that regular monitoring is essential for safety • Notify your dermatologist if you have history of tuberculosis or recurrent infections • Use reliable contraception during treatment and for 6 weeks after final dose
References
1. Bachelez H, Choon SE, Marrakchi S, et al. Trial of Spesolimab for Generalized Pustular Psoriasis. N Engl J Med. 2021;385(26):2431-2440. 2. SPEVIGO® (spesolimab) prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc.; 2022. 3. Morita A, Yamaguchi Y, Terui T, et al. Efficacy and safety of spesolimab in patients with generalized pustular psoriasis: Results from the Effisayil 1 trial. J Dermatol. 2022;49(7):678-689. 4. FDA Center for Drug Evaluation and Research. Spesolimab approval package. 2022. 5. Choon SE, Lebwohl MG, Marrakchi S, et al. Clinical and biomarker results from the phase II Effisayil 1 trial of spesolimab in generalized pustular psoriasis. Br J Dermatol. 2022;187(3):366-376.