Anakinra & Rilonacept (Kineret & Arcalyst)

Anakinra and rilonacept are two different engineering answers to the same target — the inflammatory cytokine interleukin-1 — approved seven years apart, made by unrelated companies, and used for mostly different diseases. Anakinra is a receptor antagonist that plugs the IL-1 receptor directly; rilonacept is a soluble decoy "trap" built from fused receptor fragments. They ended up, by coincidence, approved for the exact same ultra-rare genetic disease one week apart in December 2020 — the clearest illustration on this site of how two structurally different biologics can converge on identical clinical ground.

Two different ways to block the same cytokine

Interleukin-1 (IL-1) is an inflammatory cytokine that drives fever, joint destruction and tissue inflammation across a range of diseases, and anakinra and rilonacept are the two oldest FDA-approved drugs built specifically to block it — by two structurally unrelated methods. Anakinra (Kineret) is a recombinant, non-glycosylated version of the human interleukin-1 receptor antagonist (IL-1Ra), the same molecule the body makes naturally to competitively occupy the IL-1 receptor without triggering it; anakinra is essentially a manufactured surplus of that natural brake. Rilonacept (Arcalyst) works differently: it's a fusion protein combining the extracellular ligand-binding domains of the IL-1 receptor and its accessory protein with the Fc portion of human IgG1, creating a soluble decoy — an interleukin-1 "trap" — that binds circulating IL-1α and IL-1β directly, before they ever reach a cell's own receptor. Both approaches lower net IL-1 signaling; they just intercept the cytokine at different points in the same pathway. A related biologic that blocks IL-1β specifically with a full monoclonal antibody, canakinumab (Ilaris), exists but isn't covered on this site alongside these two.

Anakinra: rheumatoid arthritis first, rarer diseases later

Amgen developed anakinra and the FDA approved it on 14 November 2001 for moderately to severely active rheumatoid arthritis in patients who had already failed one or more disease-modifying antirheumatic drugs — making it the first selective IL-1 blocker ever approved for any indication. The pivotal trial randomized 419 patients on background methotrexate to placebo or one of five anakinra doses; the 1.0 mg/kg and 2.0 mg/kg groups reached ACR20 response rates of 46% and 38% respectively, versus 19% on placebo, with a statistically significant dose-response relationship (p=0.001) (Cohen S, Hurd E, Cush J, et al., "Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial," Arthritis Rheum 2002;46(3):614-624, PMID 11920396, DOI: 10.1002/art.10141).¹ Once-daily anakinra never became a first-line RA drug, though — daily self-injection and a real local injection-site-reaction rate made once-weekly TNF blockers like etanercept the more common choice, and anakinra's modern use has shifted mostly toward rarer autoinflammatory diseases: the FDA approved it for NOMID, the most severe form of CAPS, in January 2013, based on a 43-patient open-label study run at the NIH under Raphaela Goldbach-Mansky.

Rilonacept: from a CAPS drug to the first approved pericarditis medicine

Regeneron discovered rilonacept and won its first FDA approval on 27 February 2008, for two other forms of CAPS — familial cold autoinflammatory syndrome and Muckle-Wells syndrome — as a once-weekly self-injection. That approval sat as a modest, ultra-rare-disease product for nearly a decade until Regeneron licensed worldwide rights (outside Israel, Egypt, Turkey and parts of the Middle East and North Africa) to Kiniksa Pharmaceuticals in 2017, splitting future US profits evenly between the two companies. Kiniksa then ran the pivotal RHAPSODY trial in an entirely different disease — recurrent pericarditis, inflammation of the sac around the heart — testing rilonacept as a randomized-withdrawal study after initial open-label response. Patients who continued on rilonacept had a 96% reduction in the risk of a pericarditis recurrence compared with those switched to placebo, with a median time to treatment response of five days (Klein AL, Imazio M, Cremer P, et al., for the RHAPSODY Trial Investigators, "Phase 3 Trial of Interleukin-1 Trap Rilonacept in Recurrent Pericarditis," N Engl J Med 2021;384(1):31-41, PMID 33200890, DOI: 10.1056/NEJMoa2027892).² The FDA approved rilonacept for recurrent pericarditis on 18 March 2021 — the first FDA-approved therapy for that condition specifically, in adults and children 12 and older.

The same ultra-rare disease, one week apart

Deficiency of the interleukin-1 receptor antagonist (DIRA) is a genetic disease so rare that only a few dozen cases have ever been reported worldwide — patients are born unable to make functional IL-1Ra at all, leaving IL-1 signaling permanently unchecked and causing severe, potentially fatal neonatal-onset skin and bone inflammation. In December 2020, both drugs on this page picked up an FDA approval for DIRA within roughly the same week: rilonacept for maintenance of remission, and anakinra (announced by Sobi on 22 December 2020) for the disease more broadly. It's a genuine coincidence of timing rather than a coordinated launch — the two companies are unrelated and the drugs work by different mechanisms — but it means DIRA is the one indication where a patient's choice between the two IL-1 blockers on this page is a live clinical decision rather than a difference in which disease each drug happens to treat.

Anakinra's COVID-19 detour

In November 2022, the FDA granted anakinra an emergency use authorization for hospitalized COVID-19 pneumonia patients requiring supplemental oxygen who were assessed to be at risk of progressing to severe respiratory failure — based on the SAVE-MORE trial, a randomized, placebo-controlled study run in Greece. That EUA sits alongside, not in place of, anakinra's standing approvals for RA, CAPS/NOMID and DIRA, and remains tied to the broader COVID-19 public-health-emergency framework the FDA has used for other drug and biologic EUAs since 2020 — a framework HHS has said it intends to wind down, though the formal end date for drug and biologic COVID EUAs specifically has continued to be pushed back rather than fixed.

Current status

Sobi (Swedish Orphan Biovitrum) now owns and markets Kineret worldwide, having acquired the rights in stages between 2018 and 2020 from originator Amgen. Kiniksa Pharmaceuticals markets Arcalyst in the US and splits profits evenly with Regeneron under their 2017 agreement, across all three of its approved indications (CAPS, DIRA maintenance and recurrent pericarditis). Both remain routinely prescribed specialty biologics with no FDA-approved biosimilar competition established in the broad US market as of 2026, dispensed through specialty pharmacies under physician supervision — not available outside that channel in either case.