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Addition of Kineret to Methotrexate Therapy Safely, Effectively Reduces Arthritic Symptoms

Adding Kineret® to methotrexate therapy for the treatment of rheumatoid arthritis significantly improves patient outcomes, according to results from a recent multicentre, randomised, placebo-controlled study.

The cytokine, interleukin 1 (IL1), is present at elevated levels in arthritic joints of patients with rheumatoid arthritis (RA), and is likely related to the pathogenesis of this disorder. Kineret (anakinra), an IL1 receptor agonist, has demonstrated success for the treatment of RA.

To determine the ability of anakinra to safely improve outcomes in patients with inadequate response to methotrexate (MTX) therapy, Stanley Cohen, MD with the St. Paul Medical Centre, Dallas, Texas, United States, and colleagues studied an intent-to-treat population of 501 individuals, mean age 57 and mostly female, with active RA.

Patients treated with MTX for at least 24 weeks, who met the American College of Rheumatology (ACR) diagnostic criteria, were enrolled. Individuals with comorbid autoimmune disease, infection, or leukopaenia, and those receiving corticosteroids or additional anti-rheumatic drugs were excluded from the study.

Patients were randomised to add subcutaneous anakinra (100 mg/day) or placebo to 10 to 25 mg/week MTX for 24 weeks. Participants were also supplemented with folic acid. Follow up at 4-week intervals for 6 months evaluated RA characteristics and adverse effects.

Of the patients receiving anakinra, 38% achieved at least a 20% improvement in ACR composite score (ACR20) at 24 weeks, compared with 22% of those receiving MTX alone (P < .001). Similarly, the proportions of individuals demonstrating ARC50 or ARC70 in the anakinra group were more than twice as high as the MTX-only group (P < .01 and P < .05, respectively).

Odds ratios for ACR20, ACR50 and ACR70 response in the anakinra group, relative to placebo, were 2.36 (95% confidence interval (CI), 1.55-3.62), 2.61 (95% CI, 1.46-4.84), and 3.14 (95% CI, 1.16-10.06), respectively.

In addition, anakinra provided a more sustained response during follow-up. Specifically, 27% of these individuals achieved ACR20 at 4 of the 6 follow-up assessments, compared with 12% in the placebo group (P < .001).

When individual response components were evaluated, disease activity, tender/painful joint count, pain, and functional ability were all improved at 24 weeks in the patients treated with anakinra (P < .05). C-reactive protein levels and erythrocyte sedimentation rates also showed greater improvement in the anakinra group (P < .001). Swollen joint counts decreased with treatment, but improvement was similar for both groups.

No serious side effects were noted. However, a greater number of anakinra-treated patients treated had injection site reactions resulting in discontinuation.

In conclusion, the authors write, "as it is most likely that anakinra, similar to other new therapies, will be primarily used in combination with (disease-modifying anti-rheumatic drugs) such as MTX, this study confirms the previous observations of efficacy and safety of this combination."

Ann Rheum Dis 2004 Apr 13 [Epub ahead of print]. "A multicenter double-blind randomized placebo-controlled trial of Kineret(R) (anakinra), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate therapy"

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