Spevigo® - Drug Monograph
Introduction
Spevigo® (spesolimab-sbzo) is a novel humanized monoclonal antibody approved by the FDA in September 2022 for the treatment of generalized pustular psoriasis (GPP) flares in adults. It represents the first specifically approved therapy for this rare, life-threatening dermatological emergency characterized by widespread sterile pustules with systemic inflammation.
Mechanism of Action
Spesolimab-sbzo targets the interleukin-36 receptor (IL-36R), a key signaling pathway within the IL-36 cytokine system. By binding to IL-36R, spesolimab inhibits the downstream proinflammatory effects of IL-36 cytokines (IL-36α, IL-36β, and IL-36γ). This mechanism effectively interrupts the self-perpetuating inflammatory cascade responsible for neutrophil recruitment, pustule formation, and systemic inflammation characteristic of GPP flares.
Indications
- Treatment of generalized pustular psoriasis (GPP) flares in adults
Dosage and Administration
Recommended dosage: 900 mg administered via intravenous infusion Initial dose: 900 mg Additional doses: 900 mg may be administered one week after the initial dose if needed Preparation: Dilute required dose in 250 mL of 0.9% Sodium Chloride Injection Administration: Administer as an intravenous infusion over 90 minutes Special populations:- Renal impairment: No dosage adjustment recommended
- Hepatic impairment: No dosage adjustment recommended
- Elderly: No overall differences in safety or effectiveness observed
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Steady-state volume of distribution approximately 5.9 L Metabolism: Expected to undergo catabolic pathways typical of immunoglobulin G1 monoclonal antibodies Elimination: Terminal half-life approximately 20.5 days Clearance: Linear clearance approximately 0.21 L/dayContraindications
- History of serious hypersensitivity reaction to spesolimab-sbzo or any of its excipients
Warnings and Precautions
Infections: May increase risk of infections. Avoid administration in patients with clinically important active infections until resolved Tuberculosis: Evaluate patients for latent and active tuberculosis before initiating treatment Hypersensitivity reactions: Serious hypersensitivity reactions, including anaphylaxis, may occur Vaccinations: Avoid live vaccines during treatment Immunogenicity: Patients may develop anti-drug antibodiesDrug Interactions
CYP450 substrates: Monoclonal antibodies may affect CYP450 enzymes. Monitor for effects when coadministered with CYP450 substrates Immunosuppressants: Concurrent use may increase risk of infection Live vaccines: Avoid concomitant administrationAdverse Effects
Most common adverse reactions (≥5%):- Asthenia and fatigue
- Nausea and vomiting
- Headache
- Pruritus
- Infusion-related reactions
- Bruising and hematoma at infusion site
- Urticaria
- Serious infections
- Hypersensitivity reactions
- Tuberculosis reactivation
Monitoring Parameters
Before treatment:- Screen for latent and active tuberculosis
- Evaluate for active infections
- Assess vaccination status
- Monitor for signs and symptoms of infection
- Observe for hypersensitivity reactions during and after infusion
- Monitor clinical response and GPP symptoms
- Assess for development of anti-drug antibodies
- Continue monitoring for delayed hypersensitivity reactions
- Monitor for infection resolution if present before treatment
Patient Education
- Inform patients about the risk of infections and to report any signs of infection promptly
- Advise patients to seek immediate medical attention for symptoms of hypersensitivity reactions
- Discuss importance of tuberculosis screening before treatment
- Inform patients to avoid live vaccines during treatment
- Advise women of childbearing potential to use effective contraception during treatment and for at least 17 weeks after final dose
- Discuss potential side effects and management strategies
- Emphasize importance of completing all prescribed doses unless instructed otherwise by healthcare provider
References
1. Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the interleukin-36 pathway for the treatment of generalized pustular psoriasis. N Engl J Med. 2021;385(26):2431-2440. 2. Spevigo® (spesolimab-sbzo) [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2022. 3. FDA approves Boehringer Ingelheim's Spevigo® for generalized pustular psoriasis flares. FDA News Release. September 1, 2022. 4. Choon SE, Lebwohl MG, Marrakchi S, et al. Long-term efficacy and safety of spesolimab for generalized pustular psoriasis: 48-week results from the Effisayil 1 study. J Am Acad Dermatol. 2023;88(4):827-833. 5. Warren RB, et al. Spesolimab for the treatment of generalized pustular psoriasis. Expert Rev Clin Immunol. 2023;19(3):245-254.