Remission: a realistic goal in rheumatoid arthritis?

Remission in randomized clinical trials The FIN-RACo study was the first randomized controlled rheumatoid arthritis (RA) trial that used remission as the primary outcome measure [1]. In the FIN-RACo trial, remission was defined as the treatment goal and the primary outcome measure as early as 1993, years before the first biologic agent became available. Results of FIN-RACo were amazing: 42% of those who received a combination of conventional antirheumatic drugs (methotrexate [MTX], sulfasalazine [SSZ], hydroxychloroquine [HCQ] and prednisolone) for an active early RA were in remission 2 years after baseline, entirely without signs and symptoms of RA, and 68% met the disease activity index 28 (DAS28) remission criteria [2]. These findings indicated that remission is a realistic goal in RA even before the era of biologic agents. A higher remission rate than that of the FINRACo trial has only been seen in two other trials so far [3,4]. After seeing the striking results of FIN-RACo, Finnish rheumatologists were curious whether adding a biologic agent to a combination of traditional drugs would improve results. In the NEO-RACo trial, both the comparator and the active arm involved a triple therapy plus prednisolone. The active arm was intensified with half-a-year infliximab therapy. At 2 years, >80% of patients in both arms were in DAS28 remission [3]. A Dutch pilot study called ‘intensified COBRA’ involved a triple therapy plus high-dose prednisolone. Infliximab was started in six of 21 patients who did not reach a treatment target [4]. At 40 weeks, 90% of the patients were in DAS28 remission. Most randomized clinical trials (RCTs) are designed to analyze differences between active and control treatments, rather than to attain a certain clinical status such as remission. In addition to RCTs mentioned above, a few other trials have been directed to ‘tight control’ of inflammation according to a protocol that guides treatments according to clinical responses. These trials have documented that remission can be achieved in a large proportion of patients using effectively conventional antirheumatic drugs. The CIMESTRA trial required active use of glucocorticoid injections of all active joints. Remission rates were 59 and 54% for DAS28 remission and 41 and 35% for American College of Rheumatology (ACR) remission at 2 years in the combination and monotherapy arms, respectively [5]. In the TICORA trial, 65% of the tight control group and 16% in the control group were in remission according to DAS <1.6 [6]. In the BeSt study, 38–46% of patients in the four arms were in remission at the end of intervention [7]. In the CAMERA trial all patients received a monotherpy with MTX up to 30 mg. During 2 years of the study, 3-month remission periods were more often seen in patients in the computer-assisted monitoring group compared with a conventional follow-up group (50 vs 37% of patients) [8]. Two conclusions can be drawn from RCTs concerning remissions: a ‘tight control’ is a ‘remission-inducing’ strategy in patients with early RA; and remission can be achieved with a combination of MTX + SSZ + HCQ + p rednisolone in early RA in 70–80% of patients.