Introduction to the use of Kineret® (anakinra) in Rheumatoid Arthritis (RA)
The central role of IL-1 in RA
Kineret® (anakinra) is a recombinant form of the interleukin-1 receptor (IL-1Ra) antagonist, r-metHuIL-1ra, produced by recombinant DNA technology using Escherichia coli as an expression system. Kineret® (anakinra) is analogous to endogenous IL-1Ra, except for the addition of a single amino-terminal methionine residue.
Interleukin-1 (IL-1) is a major proinflammatory cytokine 1-4 , present in high concentrations in the plasma and synovial fluid of patients with rheumatoid arthritis (RA) 4-6 .
Furthermore, plasma IL-1 levels in subjects with RA have been shown to correlate with the degree of disease activity 5,6 . IL-1 is a mediator involved in many cellular immune responses, including those involved in synovial inflammation and pannus formation 7-9 . Binding of IL-1 to the interleukin-1 receptor type 1 (IL-1RI) activates signal transduction mechanisms 10,11 and, consequently, enhances the expression of a series of phlogogenic molecules involved in inflammatory processes.
» Learn more about the pathophysiology of RA
» Learn more about the key role of IL-1 in the
pathophysiology of RA
From a therapeutic point of view, Kineret® (anakinra) neutralizes the biological activity of IL-1 (IL-1α and IL-1β) by competitively inhibiting its binding to IL-1RI 10,11 .
Kineret® (anakinra) therefore prevents signal transduction as well as the production of nitric oxide, prostaglandin E2 (PGE2) and/or the production of the enzyme collagenase by synovial cells, fibroblasts and chondrocytes 12 .
» Learn more about the mechanism of action of Kineret® (anakinra)
IL-1 is a cytokine of fundamental importance in the pathophysiology of RA
Pharmacokinetics of Kineret® (anakinra)
Kineret® (anakinra) is well absorbed following subcutaneous injection. The absolute bioavailability of the drug following a 70 mg subcutaneous bolus injection in healthy subjects (n = 11) is 95%. In patients with RA, peak plasma concentrations of Kineret® (anakinra) occur 3 to 7 hours after subcutaneous administration of clinically relevant doses (1 to 2 mg/kg; n = 18) and the terminal half-life ranges from 4 to 6 hours. Furthermore, subcutaneous injection for up to 24 weeks in patients with RA did not result in any unexpected accumulation 13 .
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Kineret® (anakinra) selectively blocks the effects of IL-1 in patients with RA
Kineret® (anakinra) is a new drug effective in the treatment of RA
Kineret® (anakinra) is indicated for the treatment of the signs and symptoms of RA in combination with methotrexate (MTX), in patients with an inadequate response to MTX alone 13 . The efficacy of Kineret® (anakinra) has been evaluated in three large, multicenter, randomized, placebo-controlled clinical trials 14-17 . Considering the criteria of the American College of Rheumatology (ACR), the data emerging from these clinical trials highlight that patients treated with Kineret® (anakinra) 100 mg/day are more likely to obtain an ACR20 or greater response (ACR50 or ACR70) compared to subjects treated with placebo 14-17 . For example, 38% of patients treated with Kineret® (anakinra) achieved an ACR20 response after 24 weeks, compared with 22% of the placebo group (P<0.001) 13,14 . A clinical response to anakinra was generally evident within 2 weeks of starting treatment and was maintained with continued anakinra administration. A maximal clinical response was generally observed within 12 weeks of starting treatment 13-17 .
Kineret® (anakinra) is effective in reducing the signs and symptoms of RA
Treatment with anakinra and methotrexate in combination demonstrates a statistically significant and clinically significant reduction in the signs and symptoms of RA in patients who have had an inadequate response to MTX alone 14-16 . Additionally, Kineret® (anakinra) has demonstrated significant benefits in patient-reported assessments, as measured using the Health Assessment Questionnaire (HAQ), global assessment, and patient assessment of pain 14-16 . Additionally, significant improvements in the number of tender joints, levels of acute phase mediators, and components of the physician’s global assessment using the ACR score were observed after 24 weeks of treatment with Kineret® (anakinra) in these patient populations 14-16 .
» Read more about the efficacy of Kineret®.
The use of Kineret® (anakinra) significantly improves patient-reported assessments
Kineret® (anakinra): a new well-tolerated drug for the treatment of RA
The safety of Kineret® (anakinra) has been evaluated on the basis of an integrated pharmacovigilance database of 2606 patients with RA, including 1812 patients exposed for at least 6 months and 570 patients exposed for at least 1 year. Of these patients, 1379 received a dose of the drug greater than or equal to the recommended dose (100 mg/day) for at least 6 months and 237 patients for at least 1 year 13,14 .
In all placebo-controlled clinical trials, the most frequently reported adverse event during therapy with Kineret® (anakinra) was an injection site reaction (RSI 64.4%, n = 1399) which was mild or moderate in severity in 95% (n = 1333) of patients. The mean duration of typical RSI symptoms (erythema, bruising, inflammation and pain) was 14-28 days 13,14 .
» Read more about the safety profile of
Kineret® (anakinra).
Kineret® (anakinra) has been administered to over 2600 patients in large-scale clinical trials.
Dosage and administration
The recommended dose of Kineret® (anakinra) is 100 mg administered once daily by subcutaneous injection. Administration should be performed at approximately the same time 13 .
Role of Kineret® (anakinra) in RA therapy
Kineret® (anakinra) is a drug with a novel mechanism of action that has proven efficacy and a favorable safety profile in RA patients. Clinical data indicate that Kineret® (anakinra) is an important addition to the currently available therapeutic armamentarium for the treatment of RA patients who are inadequately responsive to MTX treatment 13 .
» Read the guidelines for the treatment of RA with
biological drugs .
Kineret® (anakinra) is an important addition to the therapeutic armamentarium available for the treatment of patients with RA who are unresponsive to treatment with MTX alone.