Lack of response to anakinra in rheumatoid arthritis following failure of tumor necrosis factor α blockade

Objective. In patients with rheumatoid arthritis (RA) treated with tumor necrosis factor alpha (TNFalpha)blocking therapy, there is heterogeneity of response. This raises the possibility that in certain circumstances, cytokines such as interleukin-1 (IL-1) may dominate the drive toward joint inflammation. This study was undertaken to investigate whether blocking the action of IL-1 with an IL-1 receptor antagonist (IL-1Ra) is efficacious in patients with disease that did not respond to TNFalpha blockade. Methods. We identified 26 RA patients whose disease had failed to respond to TNFalpha-blocking therapy, defined as failure to achieve or sustain a 20% improvement in disease activity according to the criteria of the American College of Rheumatology (ACR20 response). These patients were then treated with anakinra (100 mg/day subcutaneously) for 12 weeks, and their levels of response were assessed. Results. After 3 months of anakinra therapy, only 2 of 26 patients (8%) achieved an ACR20 response; none achieved an ACR50 or ACR70 response. A rise in the mean C-reactive protein level and an increase in the mean swollen joint count were noted during the study period. Conclusion. This study demonstrates that patients with disease that fails to respond to TNFalpha blockade also do not respond to IL-1Ra. These data do not provide evidence of a dominant role for IL-1 in patients who do not respond to TNFalpha blockade, but they do not exclude a role for other proinflammatory mediators.