Optimizing outcomes in patients with rheumatoid arthritis and an inadequate response to anti-TNF treatment.

A failure to respond to TNF inhibitors remains a serious concern for patients with RA. Although some patients experience a primary lack of drug efficacy in reducing their symptoms, others fail to maintain an initial response because of acquired drug resistance. While switching to another TNF inhibitor is a common practice for patients who are not responsive to a particular treatment, limited clinical trial data support this strategy. If more than one TNF inhibitor provides inadequate responses and/or similar tolerability issues, switching to a different class of agent may provide a more effective option. Currently four non-TNF inhibitors are approved for use in RA patients-the T-cell co-stimulation inhibitor abatacept, the B-cell-depleting mAb rituximab, the IL-1 receptor blocker anakinra and the IL-6 receptor inhibitor tocilizumab. These biologic agents have been studied in large, randomized placebo-controlled trials that demonstrate their efficacy in reducing disease activity in patients failing TNF inhibitor therapy. Results with the majority of these agents suggest that their administration may provide a greater proportion of patients with an effective, evidence-based disease-modifying approach earlier in the course of their disease than switching TNF inhibitors.