Abstract

Objectives:To incorporate a novel trial design to examine clinical response, cytokine expression, and joint imaging in rheumatoid arthritis patients switching from etanercept to infliximab.

Methods:A randomized, open-label, clinical trial of 28 patients with an inadequate response to etanercept. Eligible patients remained on background methotrexate and were randomized 1:1 to discontinue etanercept and receive infliximab 3 mg/kg at weeks 0, 2, 6, 14, and 22 or continue etanercept 25 mg twice weekly. Data were analyzed for clinical response, serum biomarker levels, radiographic progression, MRI, and adverse events.

Results:At week 16, 62% of infliximab-treated patients achieved ACR20 responses compared with 29% of etanercept-treated patients. A 30.8% decrease from baseline in disease activity score 28 was observed in patients receiving infliximab compared with a 16.0% decrease observed in patients receiving etanercept. ACR20 and ACR50 responses correlated at least minimally with intracellular adhesion molecule-1 and IL-8 in patients receiving infliximab. Thirty-eight percent of patients who were switched to infliximab showed reductions in health assessment questionnaire scores (>0.4) compared with 0% of etanercept patients. MRI analyses were inconclusive. Both drugs were well tolerated; 54% of infliximab-treated patients and 50% of etanercept-treated patients reported adverse events.

Conclusions: In this exploratory, open-label trial (with single-blind evaluator), patients were randomized to continue etanercept or switch to infliximab. The small sample size of this hypothesis- generating study was underpowered to show statistical differences between groups. There was a numerical trend favoring patients switched to infliximab, therefore warranting further study with a more rigorous design.