Kineret blocks the biologic activity of IL-1 alpha and beta by competitively inhibiting IL-1 binding to the interleukin-1 type I receptor (IL-1RI), which is expressed in a wide variety of tissues and organs.

IL-1 production is induced in response to inflammatory stimuli and mediates various physiologic responses including inflammatory and immunological responses.
IL-1 has a broad range of activities including cartilage degradation by its induction of the rapid loss of proteoglycans, as well as stimulation of bone resorption. The levels of the naturally occurring IL-1Ra in synovium and synovial fluid from RA patients are not sufficient to compete with the elevated amount of locally produced IL-1. 

Spontaneous mutations in the CIAS1/NLRP3 gene have been identified in a majority of patients with cryopyrin-associated periodic syndromes such as NOMID. CIAS1/NLRP3 encodes for cryopyrin, a component of the inflammasome. The activated inflammasome results in proteolytic maturation and secretion of IL-1β, which has an important role in the systemic inflammation and manifestations of NOMID.

Kineret is an interleukin-1 receptor antagonist indicated for: 

Rheumatoid Arthritis (RA)
• Reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis, in patients 18 years of age or older who have failed 1 or more disease modifying antirheumatic drugs (DMARDs).
Cryopyrin-Associated Periodic Syndromes (CAPS)
• Treatment of Neonatal-Onset Multisystem Inflammatory Disease (NOMID).

Rheumatoid Arthritis (RA)
• The recommended dose of Kineret for the treatment of patients with rheumatoid arthritis is 100 mg/day administered daily by subcutaneous injection. The dose should be administered at approximately the same time every day.
• Physicians should consider a dose of 100 mg of Kineret administered every other day for RA patients who have severe renal insufficiency or end stage renal disease (defined as creatinine clearance < 30 mL/min, as estimated from serum creatinine levels).

Cryopyrin-Associated Periodic Syndromes (CAPS)
• The recommended starting dose of Kineret is 1-2 mg/kg daily for NOMID patients. The dose can be individually adjusted to a maximum of 8 mg/kg daily to control active inflammation.
• Physicians should consider administration of the prescribed Kineret dose every other day for NOMID patients who have severe renal insufficiency or end stage renal disease (defined as creatinine clearance < 30 mL/min, as estimated from serum creatinine levels).

Rheumatoid Arthritis (RA)
Most common adverse reactions (incidence ≥ 5%) are injection site reaction, worsening of rheumatoid arthritis, upper respiratory tract infection, headache, nausea, diarrhea, sinusitis, arthralgia, flu like-symptoms, and abdominal pain.

NOMID
The most common AEs during the first 6 months of treatment (incidence >10%) are injection site reaction, headache, vomiting, arthralgia, pyrexia, and nasopharyngitis.

Known hypersensitivity to E coli-derived proteins, Kineret, or to any component of the product.

• In RA, discontinue use if serious infection develops. In Kineret-treated NOMID patients, the risk of a NOMID flare when discontinuing Kineret treatment should be weighed against the potential risk of continued treatment. Do not initiate Kineret in patients with active infections.
• Use in combination with Tumor Necrosis Factor (TNF) blocking agents is not recommended.
• Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported.
• The impact of treatment with Kineret on active and/or chronic infections and the development of malignancies is not known.
• Live vaccines should not be given concurrently with Kineret.
•  Neutrophil counts should be assessed prior to initiating Kineret treatment, and while receiving Kineret, monthly for 3 months, and thereafter quarterly for a period up to 1 year.