Anakinra
Also known as: AMG-719, ANAK, Anakinra, IL-1Ra recombinant, IL‑1Ra, Kineret, rhIL-1Ra
Source Anakinra at Peptiology
Save 10% with code PEPTI-BOSSRABBIT-10
Affiliate link: we earn a commission on purchases made through this link, at no extra cost to you.
Tapping Shop Now & Save 10% copies your 10% off code PEPTI-BOSSRABBIT-10 to your clipboard. Paste it at the Peptiology checkout to claim the discount.
Summary
Anakinra is a recombinant interleukin‑1 receptor antagonist approved for inflammatory diseases and administered subcutaneously or intravenously. It blocks IL‑1 signaling and is being repurposed for hyperinflammatory conditions such as secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), sepsis with macrophage activation‑like features, and refractory status epilepticus linked to cytokine storms.
Mechanism of Action
Anakinra is a human IL‑1 receptor antagonist that competitively binds the type I IL‑1 receptor, preventing IL‑1α and IL‑1β from activating the receptor complex. By blocking this interaction it suppresses downstream NF‑κB and MAP‑kinase pathways, reducing production of pro‑inflammatory cytokines, chemokines, and acute‑phase reactants that drive systemic hyperinflammation.
What the Research Shows
A 2023 systematic review of 87 patients with secondary HLH/MAS treated with intravenous anakinra reported survival comparable to historical cohorts and tolerability across a wide dosing range. In the PROVIDE sepsis trial (2022), 240 patients were stratified by immune phenotype; anakinra given to those with macrophage activation‑like syndrome or immunoparalysis improved 7‑day SOFA response versus placebo (42.9% vs 10%, p=0.042). The ImmunoSep phase III trial (2026) randomised 281 sepsis patients; intravenous anakinra in macrophage activation‑like syndrome increased the proportion achieving a ≥1.4 SOFA reduction by day 9 (35.1% vs 17.9%, p=0.002) without a mortality benefit, and noted higher anemia rates. Case series on new‑onset refractory status epilepticus (2024) described seizure control within two weeks in up to 73% of 52 patients receiving anakinra. A kidney‑amyloidosis review (2024) highlighted rare iatrogenic amyloid deposition linked to anakinra. Overall, evidence spans case reports, systematic review, and two randomized sepsis trials, indicating potential benefit in selected hyperinflammatory states.
Reported Benefits
Available data suggest anakinra can improve short‑term organ function in sepsis patients with macrophage activation‑like syndrome, achieve survival rates similar to historical controls in HLH/MAS, and provide rapid seizure control in many cases of refractory status epilepticus. The drug is generally well tolerated via both intravenous and subcutaneous routes, allowing flexibility in critically ill settings.
Limitations of the Evidence
Evidence for HLH/MAS and refractory epilepsy relies mainly on case reports and small series, limiting generalisability. Sepsis trials, while randomized, showed mixed mortality outcomes and used biomarker‑guided subgroups, so benefits may not extend to all septic patients. Dosing regimens varied, and long‑term safety, especially regarding renal amyloid deposition, remains incompletely characterised, underscoring the need for larger prospective studies.
Safety Considerations
Anakinra is usually well tolerated, but serious adverse events have been reported in critically ill cohorts, including increased incidence of anemia in sepsis trials. Rare cases of renal amyloid deposition associated with chronic use have been described. Caution is advised in patients with pre‑existing renal impairment, and routine laboratory monitoring (blood counts, renal function) is recommended during therapy.
How It Is Administered
Anakinra is supplied as a sterile solution for injection and can be given subcutaneously or intravenously. Intravenous administration is often employed in severe hyperinflammatory states, using bolus doses or continuous infusion, while subcutaneous injection is the standard route for approved indications.
Routes of Administration
Goals & Uses
- Adult-onset Still's disease (AOSD)AutoinflammatoryModerate
- Gout flare managementCrystal ArthropathyModerate
- Rheumatoid arthritisAutoimmune DiseaseHigh
- Cryopyrin‑associated periodic syndromes (CAPS)AutoinflammatoryHigh
- Cytokine storm / macrophage activation syndromeHyperinflammatoryModerate
- Juvenile idiopathic arthritisAutoimmuneModerate
- 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 infectionInfectionHigh
- Active serious infectionsInfectiousHigh
- Neutropenia (ANC <1.5×10⁹/L)HematologicHigh
- Hypersensitivity to anakinra or any excipientAllergyHigh
Adverse Effects
- EosinophiliaHematologicRare
- Injection site reactionsLocalCommon
- HeadacheNeurologicCommonPain in the head or upper neck
- Hypersensitivity/allergic reactionsImmunologicRare
- NeutropeniaHematologicUncommonLow neutrophil count
- Increased risk of malignancy (lymphoma)OncologicRare
- Serious infectionsInfectiousUncommon
- Injection‑site reactionsLocalCommon
- Infections (respiratory, urinary)SystemicCommon
Drug Interactions
- Live vaccinesHigh
- CyclosporineModerate
- Other biologic DMARDs (e.g., abatacept, tocilizumab)Moderate
- CorticosteroidsModerate
- TNF inhibitors (e.g., etanercept, adalimumab)High
- MethotrexateLow
- Concomitant immunosuppressants (e.g., methotrexate, azathioprine)Moderate
Population Constraints
- PregnancyReproductive SafetyRelative
- Pediatric patientsAgeRelative
- ElderlyAgeRelative
- 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, CAPSEMA approval; same indications.
- United StatesApprovedApproved: Rheumatoid arthritis, Cryopyrin‑associated periodic syndromesFDA approved 2001.
- United KingdomApprovedApproved: Rheumatoid arthritis, CAPSMHRA approved; marketed as Kineret.
Marketed as Kineret; approved for moderate‑to‑severe rheumatoid arthritis and CAPS; not indicated for active serious infections.
Evidence & Sources
- Journal ArticleHighCharlesworth JEG, Kavirayani A2023-01-01T00:00:00.000000Z
- Journal ArticleModerateLeventogiannis K, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateHanin A, Muscal E, Hirsch LJ2024-01-01T00:00:00.000000Z
- Journal ArticleModerateLeung N, Nasr SH2024-01-01T00:00:00.000000Z
- Journal ArticleModerateGiamarellos-Bourboulis EJ, et al.2026-01-01T00:00:00.000000Z
- Journal ArticleHighPetitdemange A, et al.2022-01-01T00:00:00.000000Z
Frequently Asked Questions
What conditions is anakinra currently approved to treat?
Anakinra is approved as a prescription medication for rheumatoid arthritis and certain autoinflammatory disorders; its use in HLH/MAS, sepsis, or refractory epilepsy is investigational and based on emerging clinical data.
How does anakinra differ from other cytokine‑targeted therapies?
Unlike antibodies that neutralise cytokines, anakinra is a recombinant protein that blocks the IL‑1 receptor itself, preventing both IL‑1α and IL‑1β from signalling and thereby dampening a broad upstream inflammatory cascade.
Is intravenous administration necessary for all patients?
Intravenous delivery is typically reserved for critically ill patients, such as those with severe HLH/MAS or sepsis, where rapid, high‑dose exposure is desired; many approved and investigational uses employ subcutaneous injection.
What monitoring is recommended during anakinra therapy?
Routine monitoring includes complete blood counts, renal function tests, and observation for signs of infection or anemia; in sepsis trials, anemia was more frequent in the anakinra arm.
Can anakinra cause kidney problems?
A recent review identified rare cases of iatrogenic amyloid deposition in the kidney linked to chronic anakinra exposure, suggesting caution and periodic renal assessment in long‑term use.
What is Anakinra?
Anakinra is a recombinant interleukin‑1 receptor antagonist approved for inflammatory diseases and administered subcutaneously or intravenously. It blocks IL‑1 signaling and is being repurposed for hyperinflammatory conditions such as secondary haemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), sepsis with macrophage activation‑like features, and refractory status epilepticus linked to cytokine storms.
What is Anakinra used for?
Anakinra is educationally associated with: Adult-onset Still's disease (AOSD), Gout flare management, Rheumatoid arthritis, Cryopyrin‑associated periodic syndromes (CAPS), Cytokine storm / macrophage activation syndrome, Juvenile idiopathic arthritis, NOMID/CINCA syndrome management, COVID-19 pneumonia with hyperinflammation, Rheumatoid arthritis disease control. Educational only — not medical advice.
How is Anakinra administered?
Recorded routes of administration: Intravenous, Subcutaneous.
What are the potential side effects of Anakinra?
Reported adverse effects include: Eosinophilia, Injection site reactions, Headache, Hypersensitivity/allergic reactions, Neutropenia, Increased risk of malignancy (lymphoma), Serious infections, Injection‑site reactions, Infections (respiratory, urinary). This list is not exhaustive — consult a qualified clinician.
Who should avoid Anakinra?
Recorded contraindications: Concurrent TNF-inhibitor therapy, Severe renal impairment (eGFR <30 mL/min), Known hypersensitivity to anakinra or E. coli-derived proteins, Active serious infection, Active serious infections, Neutropenia (ANC <1.5×10⁹/L), Hypersensitivity to anakinra or any excipient. Consult a qualified clinician before use.