Introduction
Spevigo (spesolimab-sbzo) is a novel humanized monoclonal antibody developed by Boehringer Ingelheim for the treatment of generalized pustular psoriasis (GPP) flares. It represents the first FDA-approved treatment specifically indicated for GPP flares, addressing a significant unmet medical need in dermatology. Spesolimab-sbzo received FDA approval in September 2022 based on results from the pivotal Effisayil 1 trial.
Mechanism of Action
Spesolimab-sbzo is an interleukin-36 receptor (IL-36R) antagonist that specifically binds to the IL-36 receptor, blocking the interaction of IL-36 cytokines (IL-36α, IL-36β, and IL-36γ) with their receptor. IL-36 signaling is a key driver of inflammation in GPP, contributing to neutrophil activation and recruitment, keratinocyte proliferation, and production of additional pro-inflammatory cytokines. By inhibiting IL-36 signaling, spesolimab-sbzo interrupts the inflammatory cascade that characterizes GPP flares.
Indications
- Treatment of generalized pustular psoriasis (GPP) flares in adults
Dosage and Administration
Standard dosing: 900 mg administered by intravenous infusion over 90 minutes
- May administer a second dose of 900 mg one week after the initial dose if symptoms persist
- Pre-medication with a histamine-1 receptor antagonist, acetaminophen, and a corticosteroid is recommended
Special populations:
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No dosage adjustment required
- Elderly: No dosage adjustment required
- Pediatric: Safety and effectiveness not established
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability
Distribution: Steady-state volume of distribution is approximately 5.9 L
Metabolism: Expected to be degraded via proteolytic enzymes into small peptides and amino acids
Elimination: Terminal half-life is approximately 20 days; clearance is approximately 0.29 L/day
Contraindications
- History of serious hypersensitivity reaction to spesolimab-sbzo or any of its excipients
Warnings and Precautions
- Serious infections: Increased risk of infections; do not administer to patients with active, clinically important infection
- Tuberculosis: Evaluate patients for tuberculosis infection before initiating treatment
- Hypersensitivity reactions: Serious reactions including anaphylaxis may occur
- Vaccinations: Avoid live vaccines during treatment
- Hepatic events: Monitor liver enzymes during treatment
Drug Interactions
- Live vaccines: Avoid concurrent use due to potential for reduced vaccine effectiveness and increased infection risk
- CYP substrates: Monoclonal antibodies are not expected to affect cytochrome P450 enzymes
- No formal drug interaction studies have been conducted
Adverse Effects
Most common adverse reactions (≥5%):
- Asthenia/fatigue (28%)
- Nausea and vomiting (17%)
- Headache (14%)
- Pruritus (11%)
- Infusion-related reactions (10%)
- Urticaria (8%)
- Pyrexia (6%)
Serious adverse reactions:
- Serious infections (1.7%)
- Hypersensitivity reactions
- Hepatic transaminase elevations
Monitoring Parameters
- Clinical response: Skin examination and assessment of GPP symptoms
- Infection monitoring: Signs and symptoms of infection before, during, and after treatment
- Liver function: ALT and AST at baseline and during treatment as clinically indicated
- Tuberculosis screening: Prior to initiation of therapy
- Infusion reactions: Monitor during and after infusion
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 the importance of avoiding live vaccines during treatment
- Inform patients that laboratory monitoring may be required during treatment
- Advise patients to inform all healthcare providers about their Spevigo treatment
- Discuss the potential for common side effects and management strategies
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 [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; 2022.
3. FDA approves first treatment for generalized pustular psoriasis flares. U.S. Food and Drug Administration. September 1, 2022.
4. Burden AD, Kirby B, Warren RB. Novel interleukin-36 receptor antagonist for generalized pustular psoriasis. Lancet. 2022;399(10328):802-804.
5. ClinicalTrials.gov. Efficacy and Safety of Spesolimab in Patients With Generalized Pustular Psoriasis (Effisayil 1). NCT03782792.
