Anakinra

Summary

Anakinra is a recombinant, non-glycosylated form of the human interleukin-1 receptor antagonist (IL-1Ra), differing from native IL-1Ra by the addition of a single methionine residue at the N-terminus. It is approved for rheumatoid arthritis, neonatal-onset multisystem inflammatory disease (NOMID), and COVID-19-associated pneumonia (in some jurisdictions). It blocks IL-1 signaling, reducing joint inflammation and systemic inflammatory responses.

Mechanism of Action

Competitively inhibits interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β) binding to the IL-1 type I receptor (IL-1RI), thereby blocking IL-1-mediated pro-inflammatory signaling including NF-κB activation, cytokine production, and inflammatory cascade amplification.

Routes of Administration

Goals & Uses

• Adult-onset Still's disease (AOSD)AutoinflammatoryModerate
• Gout flare managementCrystal ArthropathyModerate
• Cytokine storm / macrophage activation syndromeHyperinflammatoryModerate
• NOMID/CINCA syndrome managementAutoinflammatoryHigh
• COVID-19 pneumonia with hyperinflammationInfectious/inflammatoryModerate
• Rheumatoid arthritis disease controlAutoimmune/inflammatoryHigh

Contraindications

• Concurrent TNF-inhibitor therapyDrug Interaction/immunosuppressionHigh
• Severe renal impairment (eGFR <30 mL/min)RenalModerate
• Known hypersensitivity to anakinra or E. coli-derived proteinsAllergic/immunologicHigh
• Active serious infectionsInfectiousHigh
• Neutropenia (ANC <1.5×10⁹/L)HematologicHigh

Adverse Effects

• Injection site reactionsLocalCommon
• HeadacheNeurologicCommonPain in the head or upper neck
• Hypersensitivity/allergic reactionsImmunologicRare
• NeutropeniaHematologicUncommonLow neutrophil count
• Increased risk of malignancy (lymphoma)OncologicRare
• Serious infectionsInfectiousUncommon

Drug Interactions

• Live vaccinesHigh
• Other biologic DMARDs (e.g., abatacept, tocilizumab)Moderate
• CorticosteroidsModerate
• TNF inhibitors (e.g., etanercept, adalimumab)High
• MethotrexateLow

Population Constraints

• PregnancyReproductive SafetyRelative
• Pediatric patients (<18 years, except NOMID)AgeRelative
• Severe renal impairment (CrCl <30 mL/min) / ESRDRenalRelative
• Immunocompromised patientsImmunologicRelative
• Elderly patientsAgeRelative
• BreastfeedingReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Rheumatoid arthritis (combination with methotrexate), Neonatal-onset multisystem inflammatory disease (NOMID/CINCA), Adult-onset Still's disease (AOSD), Acute gouty arthritis (when standard therapies contraindicated), COVID-19 pneumonia requiring supplemental oxygen with elevated inflammatory markersEMA approval broader than FDA; COVID-19 indication granted conditional marketing authorization.
• United StatesApprovedApproved: Moderately to severely active rheumatoid arthritis in adults who have failed ≥1 DMARD, Neonatal-onset multisystem inflammatory disease (NOMID)FDA approved RA indication in November 2001; NOMID approved 2012 via supplemental BLA. Black Box Warning for serious infections and malignancy risk.
• United KingdomApprovedApproved: Rheumatoid arthritis, NOMID/CINCA, Adult-onset Still's disease, Acute gouty arthritisMHRA approved; aligned largely with EMA indications post-Brexit. COVID-19 indication subject to separate review.

FDA-approved for rheumatoid arthritis (2001) and NOMID (2012). EMA-approved for RA and NOMID; also approved in EU for COVID-19-associated pneumonia. Carries a Black Box Warning regarding serious infections and increased risk of lymphoma.

Evidence & Sources

No sources recorded yet.