Maxime Verhoeven

105 Effectiveness and safety of treat-to-target strategies over 5 years INTRODUCTION The current guidelines for the treatment of rheumatoid arthritis (RA) recommend treating to target, aiming for remission, to reduce the risk of disability and improve long- term outcomes. With this aim, generally, a conventional synthetic disease modifying anti-rheumatic drug (csDMARD) is started immediately after diagnosis. If the treatment target is not achieved within 3-6 months, another csDMARD or a biological (b)DMARD is added. 1 Several placebo-controlled randomized controlled trials (RCTs) in early RA patients compared the effects of initial treatment strategies using a bDMARD to those of initial treatment strategies with only (a) csDMARD(s), mostly methotrexate (MTX). 2–8 In the short term (<1 year), disease control and outcomes, including progression of joint damage and physical function, were better in strategies initiating a bDMARD with or without a csDMARD. The first RCT of initiation of the bDMARD tocilizumab (TCZ) in DMARD-naïve early RA patients showed that more patients receiving TCZ(+/- MTX) achieved remission at 24 and 52 weeks compared with patients receiving MTX. 6 However, this was not a treat-to-target design like the U-Act-Early trial. In this 2-year trial involving early DMARD- and glucocorticoid (GC)-naïve RA patients with the treatment target of sustained remission (SR), efficacy and safety of step-up treatment strategies initiating treatment with TCZ, MTX or their combination were compared. When the treatment target was achieved, medication was tapered and eventually stopped, if patients remained in remission. Outcomes of U-Act-Early were in line with those of other RCTs showing improved effectiveness for strategies initiating/adding a bDMARD from the start of therapy, compared with strategy groups not including a bDMARD from the start. 9 For example, SR was achieved earlier in the TCZ strategy groups in the U-Act-Early trial. 10 However, starting TCZ immediately upon diagnosis in early RA patients does not accord with the current disease management recommendations. To justify initiation of (expensive) bDMARDs directly after diagnosis, not only clear advantages in the first months, but also a longer-term effectiveness would be warranted. Therefore, patients in the U-Act-Early trial were followed for another 3 years, to determine longer-term effectiveness. We hypothesized that during this follow-up period, the disease activity score assessing 28 joints (DAS28, based on erythrocyte sedimentation rate (ESR)) would remain similar (continuing the treat-to-target approach) between the initial strategy groups, and that radiographic progression would be less in patients who had initiated TCZ (+/- MTX) compared with those who had initiated MTX. Moreover, based on the finding that during the 2-year trial TCZ use steadily increased in the MTX initiation strategy group and decreased in the 2 TCZ initiation strategy groups, we hypothesized 6