Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease caused by a combination of genetic and environmental factors which primarily affects the joints.1 RA is estimated to affect 0.5–1% of the worldwide population, although variation in prevalence has been reported across geographies and ethnicities.1 The aim of RA treatment is to achieve remission or minimal disease activity, using a treat to target approach.2,3
European Alliance of Associations for Rheumatology (EULAR) and American Colleague of Rheumatology (ACR) consider methotrexate to be the ‘anchor’ drug in RA, either as monotherapy (first-line DMARD) or in combination with other drugs (glucocorticoids, other csDMARDs, bDMARDs, or tsDMARDs).2,3
The EULAR definition of difficult-to-treat requires presence of three criteria: failure of ≥2 b/ts DMARDs (different MoA), signs of active/progressive disease, and perception by the rheumatologist and/or patient that disease management has become problematic.
All three of the following criteria need to be present:
Though RA is primarily defined as an autoimmune disease, patients with difficult-to- treat RA may have a pronounced autoinflammatory component to their disease. If your patient has tried and failed multiple RA treatments, their disease may be driven by autoinflammation. Interleukin-1 (IL-1) may be a driver of that inflammation.8,9
Adapted from: Figure 1, McGonagle, et al. Mechanistic immunological based classification of rheumatoid arthritis.
A few general criteria may provide important context for identifying if any of your patients have predominantly autoinflammatory RA.
Kineret is a valuable asset for the treatment of refractory RA.13 Kineret blocks the interleukin-1 (IL-1) receptor to help protect against autoinflammatory events.11
The safety and efficacy of anakinra in combination with methotrexate have been demonstrated in 1790 RA patients ≥ 18 years of age with varying degrees of disease severity.11
Kineret is indicated in adults for the treatment of the signs and symptoms of RA in combination with methotrexate, with an inadequate response to methotrexate alone. A clinical response to anakinra generally appears within 2 weeks of initiation of treatment and is sustained with continued administration of anakinra. Maximal clinical response is generally seen within 12 weeks after starting treatment.11
Kineret was studied in patients with active RA
This randimised, double-blind, placebo-controlled trial was conducted on 899 patients with active RA who had been on a stable dose of methotrexate (10-25 mg/ week) for at least 8 weeks. Patients were randomised to Kineret (n=250) or placebo (n=251) in addition to their stable doses of methotrexate. The first 501 patients were evaluated for signs and symptoms of active RA.14
At month 6, ~1 in 4 patients achieved a minimum of ACR50 (23%)* following treatment with Kineret compared to placebo (10%).14
Adapted from: Figure 1 A, Cohen et al. A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate
Radiographic changes improved over the course of 1 year with Kineret
The effect of Kineret on the progression of structural damage was assessed by measuring the change from baseline at month 12 in the Total Modified Sharp Score (TMSS) and its subcomponents, erosion score (ES), and joint space narrowing (JSN) score. Radiographs of hands/wrists and forefeet were obtained at baseline, 6 months, and 12 months and scored by readers who were unaware of treatment group. Differences between placebo and Kineret for change in TMSS, ES, and JSN score were observed at 12 months.14
The disability index of the Health Assessment Questionnaire (HAQ) was administered monthly for the first 6 months and quarterly thereafter during the study.14
Health outcomes were assessed by the Short Form-36 (SF-36) questionnaire. The 1-year data on HAQ in Study 1 showed more improvement with Kineret than placebo. The physical component summary score of SF-36 also showed more improvement with Kineret than placebo but not the mental component summary.14
Adapted from: Table 5, Kineret US Prescribing information
Abbreviations
csDMARD, conventional synthetic disease-modifying antirheumatic drug; bDMARD, biologic disease-modifying antirheumatic drug; tsDMARD, targeted synthetic disease-modifying antirheumatic drug; TNF, tumor necrosis factor; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; MTX, methotrexate.