Decreased pain and synovial inflammation after etanercept therapy in patients with reactive and undifferentiated arthritis: An open-label trial

Objective. Elevated levels of tumor necrosis factor alpha (TNF alpha) have been identified in the synovium of patients with reactive and undifferentiated arthritis, implicating TNF alpha in the pathogenesis of these disorders. This finding has provided a rationale for the use of TNF alpha antagonists in the treatment of reactive arthritis; however, the possibility that the triggering microorganism might persist in affected joints and become activated with use of these agents has been of concern. Methods. The efficacy and safety of etanercept (25 mg subcutaneous twice weekly) in 16 patients with undifferentiated or reactive arthritis was assessed in a 6-month open-label trial. Synovial biopsies were performed before and after treatment with etanercept. Polymerase chain reaction (PCR) analysis was performed on the synovial biopsy samples to evaluate for the presence of nucleic acid material of bacterial organisms. Outcome measures including tender and swollen joint counts, pain assessment on a 10-point visual analog scale, and functional ability as measured by the Health Assessment Questionnaire were determined before and after etanercept therapy. Results. Ten of 16 patients completed the trial. Six patients withdrew, but none had a worsening of arthritis or infection. Of the 10 completers, 9 could be classified as treatment responders, despite the evidence of bacterial organisms on PCR analysis prior to initiating etanercept in 3 patients; 2 patients became PCR negative on etanercept. Five of 6 patients with adequate synovial biopsy specimens showed improvement, but not normalization of histology. Conclusion. Etanercept was well-tolerated without clinical exacerbation of any suspected underlying infections and appeared to provide therapeutic benefit in our cohort of patients with reactive and undifferentiated arthritis.