Kineret - Drug Monograph

Introduction

Kineret (anakinra) is a recombinant human interleukin-1 receptor antagonist (IL-1Ra) approved by the FDA in 2001. It represents a targeted biologic therapy that specifically modulates the inflammatory pathway involved in several autoimmune conditions. Kineret is manufactured by Swedish Orphan Biovitrum (Sobi) and is administered via subcutaneous injection.

Mechanism of Action

Kineret works by competitively inhibiting the binding of interleukin-1 (IL-1) to its type I receptor. IL-1 is a potent proinflammatory cytokine produced in response to inflammatory stimuli. By blocking IL-1 from binding to its receptors throughout the body, anakinra reduces the inflammatory response mediated by IL-1. This mechanism is particularly relevant in conditions where IL-1 plays a central pathophysiological role, such as in cryopyrin-associated periodic syndromes (CAPS) and rheumatoid arthritis.

Indications

FDA-approved indications:

• Moderate to severe active rheumatoid arthritis (RA) in adults who have failed one or more disease-modifying antirheumatic drugs (DMARDs)
• Neonatal-onset multisystem inflammatory disease (NOMID)
• Deficiency of IL-1 receptor antagonist (DIRA)
• Familial cold autoinflammatory syndrome (FCAS)
• Muckle-Wells syndrome (MWS)

Off-label uses include:

• Adult-onset Still's disease
• Gout
• Recurrent pericarditis
• Systemic juvenile idiopathic arthritis

Dosage and Administration

• Rheumatoid arthritis: 100 mg subcutaneously once daily
• CAPS spectrum disorders:

- FCAS/MWS: 100 mg subcutaneously once daily (may increase to 200-300 mg daily in divided doses) - NOMID: 1-2 mg/kg initially, titrated up to 8 mg/kg daily (maximum 300 mg daily)

• Administer subcutaneously in the thigh, abdomen, or upper arm
• Rotate injection sites
• Allow refrigerated medication to reach room temperature (30 minutes) before injection

• Renal impairment: Use with caution; consider dose reduction for CrCl < 30 mL/min
• Hepatic impairment: No dose adjustment required
• Elderly: Monitor closely due to increased infection risk
• Pediatrics: Weight-based dosing for CAPS indications

Pharmacokinetics

Contraindications

• Hypersensitivity to anakinra, E. coli-derived proteins, or any component of the formulation
• Active infections
• Concomitant use with tumor necrosis factor (TNF) blocking agents (increased risk of serious infections)
• Live vaccinations during treatment

Warnings and Precautions

• Monitor for signs and symptoms of infection during and after treatment
• Increased risk of infection in patients with comorbid conditions
• Neutropenia (particularly when used with TNF blockers)
• Immunosuppression may affect defense against malignancies
• Hypersensitivity reactions (rare but reported)
• Use in pregnancy only if clearly needed (Category B)
• Caution in patients with renal impairment

Drug Interactions

• TNF-blocking agents (increased risk of serious infections - contraindicated)
• Other immunosuppressive drugs (additive immunosuppression)
• Live vaccines (avoid concurrent use)
• Etanercept (specifically shown to increase serious infection risk without added benefit)

• Methotrexate
• Corticosteroids
• NSAIDs

Adverse Effects

• Injection site reactions (erythema, ecchymosis, inflammation, pain) - 71%
• Headache
• Upper respiratory infections

• Sinusitis
• Flu-like symptoms
• Nausea
• Diarrhea
• Arthralgia
• Neutropenia (especially when combined with other immunosuppressants)

• Serious infections (pneumonia, cellulitis)
• Neutropenia (<1 × 10⁹/L)
• Hypersensitivity reactions
• Anaphylaxis

Monitoring Parameters

• Complete blood count with differential
• Renal function tests
• Hepatitis and tuberculosis screening
• Pregnancy test if appropriate

• Signs/symptoms of infection at each visit
• CBC with differential monthly for 3 months, then quarterly
• Neutrophil count (discontinue if ANC < 0.5 × 10⁹/L)
• Injection site reactions
• Disease activity assessment
• Renal function in patients with preexisting impairment

• Lipid profile (may improve with inflammation control)
• Bone mineral density (chronic inflammation effects)
• Malignancy screening per standard guidelines

Patient Education

• Proper injection technique and site rotation
• Storage requirements (refrigeration at 2-8°C)
• Allow medication to reach room temperature before injection
• Dispose of needles and syringes properly

• Report any signs of infection immediately (fever, cough, flu-like symptoms)
• Avoid people with infections when possible
• Inform all healthcare providers about Kineret use
• Do not receive live vaccines during treatment
• Report injection site reactions that persist or worsen

• Importance of consistent dosing schedule
• Do not stop medication without consulting prescriber
• Carry medical identification indicating immunosuppressive therapy
• Discuss family planning if considering pregnancy

References

1. FDA Prescribing Information: Kineret (anakinra). Revised 2020. 2. Fleischmann RM, et al. Arthritis Rheum. 2003;48(4):927-934. 3. Hawkins PN, et al. N Engl J Med. 2003;348(25):2583-2584. 4. Mertens M, Singh JA. Anakinra for rheumatoid arthritis. Cochrane Database Syst Rev. 2009;(4):CD005121. 5. ter Haar NM, et al. Ann Rheum Dis. 2013;72(6):806-812. 6. Hoffman HM, et al. N Engl J Med. 2008;358(8):810-820. 7. Dinarello CA, et al. Nat Rev Drug Discov. 2012;11(8):633-652. 8. ClinicalTrials.gov: Various studies on anakinra safety and efficacy. 9. American College of Rheumatology Guidelines for RA Treatment: 2021 Update. 10. European League Against Rheumatism (EULAR) recommendations for RA management: 2022 update.