Background/Purpose: After demonstration of effectiveness of anti-tumor necrosis factor (TNF) agents in patients with rheumatoid arthritis (RA), their use has become common practice in treating patients not responding to classical disease modifying anti-rheumatic drugs (DMARDs). In this paper, we studied the long-term clinical outcome of infliximab, which is first biological DMARD for RA in Japan, to demonstrate the �ereal-world’ data using our registry system. To accumulate the data from daily clinical practice is quite important to improve the treatment strategy for RA.

Methods: All eligible patients were registered in the Tsurumai Biologics Communication Registry (TBCR), an RA research consortium that consists of Nagoya University Hospital and 12 affiliated institutes. As of September 2011, 2,176 RA patients treated with biologics are registered in this registry system. Four hundred forty seven RA patients previously unexposed to biological DMARDs were treated with infliximab (IFX). Drug retention rates were calculated by Kaplan-Meier method using endpoint of inefficacy or adverse events.

Results: As baseline characteristics, mean age was 56.6 years, disease duration was 14.9 years, proportion of patients with methotrexate was 99.6%, MTX dose was 7.2 mg/week, proportion of patients with prednisolone (PSL) was 76.1%, PSL dose was 5.2 mg, serum C-reactive protein was 3.8 mg/dL, and DAS28 was 5.7. IFX retention rate was 67.5% at 1 year, 31.0% at 5 years, and 22.5% at 8 years (Fig. a). IFX discontinuation rate due to inefficacy was 58.1% (Fig. b). Primary inefficacy was seen in 6.9% and secondary inefficacy was seen in 27.1% of patients. Discontinuation rate due to adverse events was 42.7% at 8 years (Fig. c). Most frequent adverse events resulted in IFX discontinuation was pulmonary complication (9.8%) including interstitial pneumonia (IP, 2.5%), bacterial pneumonia (4.3%), pulmonary tuberculosis (1.1%), pneumocystis pneumonia (0.7%), and organizing pneumonia (0.4%). The second most frequent was infusion reaction seen in 7.8%. The incidence of malignant neoplasm was seen in 1.8%.

Conclusion: We observed quite high discontinuation rate due to secondary inefficacy. This is probably dependent on the relatively low MTX dose, because of the Japanese regulation of public health insurance coverage. We are convinced of improved discontinuation rate if only with higher dose of concomitant MTX, which would reduce the production of anti-IFX antibodies resulting in secondary inefficacy and infusion reaction. It was the important data that the most frequent adverse events resulting in discontinuation was pulmonary complications. Putting all our results together, we would suggest that the most suitable patients for IFX treatment, expecting long-tern adherence, would be ones using sufficient dosage of concomitant MTX treatment and do not have baseline comorbidity of pulmonary diseases.