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Interleukin 1 inhibitors

	Anakinra	Canakinumab	Rilonacept
Target	IL-1alpha, IL-1beta	IL-1beta	IL-1alpha, IL-1beta*
Mechanism of action	IL-1ra	Anti-IL-1beta	IL-1 "trap" fusion protein
IgG isotype	N/A	IgG1, kappa	IgG1 (heavy chains only)
Half-life	4 to 6 hours	26 days	7 days
Administration	Subcutaneous (IV)	Subcutaneous^¶	Subcutaneous
Administration interval	Daily	Every 1 to 2 months	Weekly
Renal dose adjustment	Yes	No	No
Antiinflammatory potency	+++	+++	++
FDA-approved indications	CAPS Rheumatoid arthritis	CAPS TRAPS HIDS/MKD FMF Systemic JIA Adult-onset Still's disease	CAPS DIRA Recurrent pericarditis
EMA-approved indications	CAPS FMF Systemic JIA Adult-onset Still's disease Rheumatoid arthritis	CAPS TRAPS HIDS/MKD FMF Systemic JIA Adult-onset Still's disease Gout flare	None
Common off-label uses (in addition to FDA- and EMA-approved uses)	Gout flare Recurrent pericarditis Macrophage activation syndrome
Select adverse effects	Injection site reactions Acute and subacute hepatitis Infections Neutropenia	Injection site reactions Acute infections Neutropenia	Injection site reactions Undefined acute infection risk Hyperlipidemia

IL-1: interleukin 1; IL-1ra: IL-1 receptor antagonist; IgG: immunoglobulin G; IV: intravenous; FDA: US Food and Drug Administration; CAPS: cryopyrin-associated periodic syndromes; TRAPS: tumor necrosis factor receptor-associated periodic syndrome; HIDS/MKD: hyperimmunoglobulin D syndrome/mevalonate kinase deficiency; FMF: familial Mediterranean fever; JIA: juvenile idiopathic arthritis; DIRA: deficiency of interleukin 1 receptor antagonist; EMA: European Medicines Agency.
* Rilonacept also binds endogenous IL-1ra with a lower affinity than for IL-1alpha and IL-1beta.
¶ Intravenous administration has been used on an investigative basis.

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