DISCONTINUATION OF ETANERCEPT IN EARLY RHEUMATOID ARTHRITIS PATIENTS WHO HAVE ACHIEVED SUSTAINED REMISSION: RESULTS OF THE RANDOMIZED CONTROLLED TRIAL IN PERIOD 2 OF THE ENCOURAGE STUDY

Abstract

Background It has been argued whether anti-TNF treatment can be discontinued after the introduction of clinical remission. The ENCOURAGE study has been conducted as an international, multi-institutional prospective study to demonstrate the efficacy and safety of etanercept (ETN) plus methotrexate (MTX) treatment in early RA patients with moderate disease activity (Period 1), and to explore the possibility of discontinuing ETN in patients who have achieved sustained clinical remission.

Objectives Period 2 of the ENCOURAGE study was conducted to investigate the maintenance of sustained remission for 1 year after randomization to determine whether to continue or discontinue ETN.

Methods This was a multi-center study, comprising 30 institutes (28 in Japan, 2 in Korea), to investigate the optimal therapeutic strategy for RA patients who had an incomplete response to MTX, moderate disease activity, and a disease duration5 years (n=225, Period 1). A total of 99 patients who maintained clinical remission for 6 months with ETN plus MTX in Period 1 were randomly allocated to either the ETN continuation (C) or discontinuation (D) arm. Resumption of ETN therapy at any time was allowed in arm D, but these patients were excluded from the analysis. The primary endpoint was the remission rate after 1 year, and the analysis was conducted using LOCF or linear extrapolation.

Results Ninety-nine patients were randomized into either the ETN continuation (C, n=49) or discontinuation (D, n=50) arm. There was no significant difference in baseline disease duration (C: 1.9, D: 2.4 years), DAS28 (1.7, 1.8) or HAQ (0.1, 0.1). At 6 or 12 months after randomization, 90.6 or 87.5% of patients in arm C and 64.3 or 53.6% of patients in arm D maintained clinical remission. No significant radiological progression of joint damage was demonstrated in 89.7% of patients in arm C and 82.6% in arm D; 90.9% of patients in arm C completed the protocol, and 58.9% of arm D completed the protocol without resuming ETN.

Conclusions Early RA patients who had achieved sustained remission after administration of ETN plus MTX maintained remission through the continuation of this treatment combination; however, more than half of the patients maintained sustained remission even after discontinuation of ETN.