Canakinumab - Drug Monograph

Introduction

Canakinumab (brand name Ilaris®) is a fully human monoclonal antibody that specifically targets interleukin-1 beta (IL-1β), a key proinflammatory cytokine. It belongs to the class of biologic disease-modifying antirheumatic drugs (bDMARDs) and represents a targeted approach to managing several autoinflammatory conditions characterized by dysregulated IL-1β signaling.

Mechanism of Action

Canakinumab binds with high affinity and specificity to human IL-1β, preventing its interaction with IL-1 receptors. By neutralizing IL-1β activity, canakinumab inhibits the cytokine-induced inflammatory cascade, including reduced production of inflammatory mediators such as C-reactive protein (CRP), serum amyloid A, and IL-6. This mechanism effectively interrupts the pathophysiological processes driving systemic inflammation in autoinflammatory disorders.

Indications

FDA-approved indications:

• Cryopyrin-Associated Periodic Syndromes (CAPS): Familial Cold Auto-inflammatory Syndrome (FCAS), Muckle-Wells Syndrome (MWS)
• Systemic Juvenile Idiopathic Arthritis (SJIA) in patients aged 2 years and older
• Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)
• Hyperimmunoglobulin D Syndrome (HIDS)/Mevalonate Kinase Deficiency (MKD)
• Familial Mediterranean Fever (FMF)
• Gouty Arthritis (investigational use for cardiovascular risk reduction)

Dosage and Administration

• CAPS: 150 mg for most adults and children ≥40 kg; 2 mg/kg for children 15-40 kg; 4 mg/kg for children 7.5-15 kg subcutaneously every 8 weeks
• SJIA: 4 mg/kg (maximum 300 mg) subcutaneously every 4 weeks
• TRAPS, HIDS/MKD, FMF: 150 mg every 4 weeks for patients ≥40 kg; 2 mg/kg every 4 weeks for patients 7.5-40 kg

• Subcutaneous injection only
• Rotate injection sites (thigh, abdomen, upper arm)
• Allow refrigerated medication to reach room temperature (30 minutes) before injection
• Do not shake the solution

• Renal impairment: No dosage adjustment required
• Hepatic impairment: No specific recommendations
• Elderly: Use with caution due to increased infection risk
• Pediatrics: Dosing based on weight as specified

Pharmacokinetics

Contraindications

• Hypersensitivity to canakinumab or any component of the formulation
• Active, serious infections
• History of anaphylaxis to canakinumab
• Concurrent live vaccines during treatment

Warnings and Precautions

• Screen for tuberculosis before initiation
• Monitor for signs of infection during and after treatment
• Interrupt therapy if serious infection develops

Drug Interactions

• TNF blockers: Increased risk of serious infections (avoid concomitant use)
• Other IL-1 blockers: No clinical experience with combination therapy
• Live vaccines: Avoid concurrent administration
• Cytochrome P450 substrates: May normalize metabolism of drugs metabolized by CYP450 enzymes due to reduced inflammation

Adverse Effects

• Upper respiratory tract infections
• Injection site reactions (erythema, pain, swelling)
• Gastroenteritis
• Nasopharyngitis
• Headache
• Diarrhea

• Serious infections (pneumonia, cellulitis)
• Anaphylaxis
• Neutropenia
• Thrombocytopenia
• Macrophage activation syndrome
• Increased liver enzymes

Monitoring Parameters

• Complete blood count with differential
• Liver function tests
• Tuberculosis screening
• Hepatitis B and C screening
• Baseline inflammatory markers (CRP, ESR)

• Signs and symptoms of infection at every visit
• Inflammatory markers (monthly initially, then as clinically indicated)
• Complete blood count (periodically)
• Liver function tests (periodically)
• Clinical assessment of disease activity
• Injection site reactions

• Annual tuberculosis screening in endemic areas
• Vigilance for malignancy development
• Growth parameters in pediatric patients
• Lipid profile (particularly in cardiovascular studies)

Patient Education

• Proper injection technique and site rotation
• Storage requirements (refrigeration, protection from light)
• Never share injection devices

• Report any signs of infection (fever, cough, sore throat, urinary symptoms)
• Seek immediate medical attention for serious infection symptoms
• Avoid close contact with people with active infections

• Inform all healthcare providers about canakinumab use
• Carry medical identification indicating current therapy
• Report any allergic reactions or injection site problems
• Discuss vaccination needs before starting treatment
• Notify physician if pregnancy is planned or suspected

• Keep all scheduled medical appointments
• Report any new or worsening symptoms promptly
• Do not discontinue medication without medical guidance

References

1. FDA Prescribing Information: Ilaris® (canakinumab) 2. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11(8):633-652. 3. Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360(23):2416-2425. 4. Ruperto N, Brunner HI, Quartier P, et al. Two randomized trials of canakinumab in systemic juvenile idiopathic arthritis. N Engl J Med. 2012;367(25):2396-2406. 5. De Benedetti F, Gattorno M, Anton J, et al. Canakinumab for the treatment of autoinflammatory recurrent fever syndromes. N Engl J Med. 2018;378(20):1908-1919. 6. Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377(12):1119-1131. 7. National Institute for Health and Care Excellence (NICE) guidance: Canakinumab for treating systemic juvenile idiopathic arthritis (TA299)