Abstract and Introduction
Abstract
Objective To assess the efficacy and safety of abatacept in biological-naive patients with rheumatoid arthritis and an inadequate response to methotrexate treated in the long-term extension (LTE) of the ATTEST trial.
Methods Patients randomly assigned to abatacept, placebo or infliximab completing the 1-year double-blind period were eligible to receive abatacept ~10 mg/kg in the open-label LTE. Efficacy to year 2 is presented for patients randomly assigned to abatacept or infliximab who switched to open-label abatacept. Safety data are presented for all patients entering LTE regardless of double-blind treatment.
Results Of 431 patients randomly assigned, 79.8% remained on abatacept at year 2. At years 1 and 2, 19.7% and 26.1% of abatacept and 13.3% and 28.6% of infliximab-to-abatacept patients achieved disease activity score 28-defined remission (<2.6). Safety with abatacept during the cumulative study period was consistent with the double-blind experience, with no increase in adverse event incidence following the switch to abatacept.
Conclusion In methotrexate-inadequate responders, abatacept efficacy was maintained over 2 years. For infliximab-to-abatacept patients, efficacy improvements were seen in year 2 after patients switched to abatacept. Switching directly from infliximab to abatacept was well tolerated. These data demonstrate that abatacept provides sustained responses and consistent safety, suggesting that switching from infliximab to abatacept is a viable treatment option.
Introduction
Randomised clinical trials have assessed the efficacy and safety of switching to abatacept (T-cell costimulation modulator), rituximab (B-cell depleting therapy) or tocilizumab (interleukin-6 inhibitor) after failure of anti-tumour necrosis factor (TNF) agents. However, there is a paucity of information on the efficacy and safety of switching from one mechanism of action to another in patients who have not failed previous anti-TNF therapy due to lack of efficacy.
The Abatacept or infliximab versus placebo, a Trial for Tolerability, Efficacy and Safety in Treating rheumatoid arthritis (ATTEST) trial provided a unique opportunity to assess clinical efficacy and safety outcomes in biological-naive patients who switched from an anti-TNF to abatacept, regardless of earlier treatment response - that is including both patients in high, moderate or low disease states, or with American College of Rheumatology (ACR) 20, 50 or 70 responses, at the end of 12 months of infliximab treatment. Such observations could help inform clinical decision-making following treatment withdrawal for either safety or efficacy-related reasons. In the 1-year double-blind period of ATTEST, although a greater proportion of patients achieved ACR20 at month 1 with infliximab versus abatacept, by month 3 responses were similar. Both biological agents demonstrated comparable efficacy compared with placebo at 6 months; further improvements were observed with abatacept over 1 year. there were numerically fewer serious adverse events (SAE) and serious infections with abatacept versus infliximab over 1 year.
Here, we report the efficacy and safety from the 1-year open-label long-term extension (LTE) of ATTEST, in which all patients received open-label abatacept, regardless of double-blind treatment or treatment response.