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Anakinra is worth trying in RA after TNF inhibitors fail

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Two previous reports have suggested that patients with rheumatoid arthritis who have failed to respond to treatment with TNF inhibitors are unlikely to respond to the interleukin-1 antagonist anakinra (Kineret, Amgen). However, both reports were based on experience with only 26 patients, and other clinicians have told rheumawire of anecdotal cases they have had of such patients responding and doing well.

Now, a report from a “real-world” database that included 192 such patients concludes that anakinra may be of benefit and is worth considering in RA patients who have not responded to TNF-inhibitor therapy. The new data, reported by Dr Michael Schiff (Denver Arthritis Center, CO) in a letter in the January 2005 issue of Arthritis & Rheumatism, come from the Rheumatoid Arthritis DMARD Intervention and Utilization Study (RADIUS 1). This is a prospective multicenter observational study designed to systematically document use patterns, effectiveness, and safety of disease-modifying antirheumatic drugs (DMARDs) used in the treatment of RA, Schiff explains. Between October 2001 and December 2002, this study enrolled around 5000 RA patients who needed a new DMARD (either a switch or an add-on) from 389 sites across the US.Good candidates for anakinra therapy?An ad hoc analysis found 192 patients who started on anakinra and who had previously been treated with a TNF inhibitor; most had discontinued because of lack of efficacy (46.9%) and/or adverse effects (40.1%). The mean disease duration was 11.2 years, and patients had received a mean of 3.2 prior DMARDs. Of these 192 patients, most had tried only 1 TNF inhibitor, but 48 patients had tried 2 agents; as expected, these patients were considered by their physicians to have more severe disease, Schiff comments. Overall, these patients demonstrated improvements in all efficacy measures after 6 months of anakinra therapy and, despite the need for daily injections, continued to receive anakinra at 6 months, Schiff reports. Significant improvements were seen in tender- and swollen-joint counts, morning stiffness, and pain scores and on both physician and patient global assessments. Patients who had discontinued 2 prior TNF inhibitors showed a “more robust improvement” with anakinra therapy in patient-reported outcomes than those who had previously tried only 1 TNF inhibitor, Schiff notes. However, he suggests that it is the patients who discontinued TNF inhibitors for safety reasons that may be good candidates for anakinra therapy, based on “its excellent safety profile and current efficacy results.” Would previous failures have responded to anything? Another reason for the previous negative findings, in addition to the small numbers involved, may be that the patients who were being treated had disease that was more severe that that of patients seen typically at a rheumatology practice, Schiff suggests. He notes that the series of 26 patients reported by the UK team [2] had an average disease duration of >15 years and had tried 5 prior DMARDs. “Patients with these disease characteristics are not likely to respond to any treatment,” he comments. In a reply [3], the UK team, headed by Dr Paul Emery (University of Leeds), agrees with both comments but points out that their study was prospective and had clearly defined outcomes and very well-defined patient characteristics. The participants were chosen specifically not only because they had failed TNF-inhibitor therapy but also because the majority (23 of 26 patients) had primary inefficacy of TNF blockade. Because they had a pure nonresponse to TNF inhibitors, they could have reasonably been expected to have a more interleukin-1-driven disease, the team writes. But they had virtually no measurable response to anakinra, and in fact had an outcome that was worse than that seen in comparable patients not selected for TNF-blockade resistance. “We concur that patients who have discontinued TNF-antagonist therapy for safety reasons may respond to anakinra therapy,” say Emery et al. But they add: “We still strongly believe that patients with primary failure to TNF blockade are not those with an IL-1-driven disease.”(Source: JointandBone, February 2005)

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Posted On: 6 February, 2005
Modified On: 16 January, 2014

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