Maxime Verhoeven

21 Systematic review of remission-induction strategies in early RA INTRODUCTION In rheumatoid arthritis (RA), early initiation of disease modifying anti-rheumatic drug (DMARD) treatment, preferably within the ‘window of opportunity’, is thought to optimally prevent joint damage, improving long-term outcome and quality of life. 1,2 Accordingly, current international guidelines advice to start treatment in early RA as soon as possible after diagnosis. Initial therapy is started with a conventional synthetic (cs)DMARD, most frequently methotrexate (MTX), in a ‘tight-controlled’ manner, aiming for low disease activity or, preferably, remission. 1,3 Initial MTX therapy is sometimes combined with short-term use of moderate-high dose glucocorticoids (GCs), which are then tapered as soon as possible: GC bridging therapy. The treatment strategy has to be intensified if the treatment target is not achieved within 6 months. 1,3 This next step is often to add a biological (b) or targeted small molecule (ts) DMARD. 4,5 Previous research shows that approximately 30-50% of early RA patients need additional b/tsDMARD therapy. 6 Patients who initiate a more intensive DMARD strategy as first-line treatment than that according to current guidelines as described above, have sometimes shown superior effectiveness outcomes, and achieve remission more often and earlier, sometimes also including sustained remission (SR) and even sustained drug free remission (sDFR), which may thus become achievable treatment targets. 4,7 Achieving remission earlier has been found to be related to improved long-term outcomes. 7 Furthermore, SR and sDFR may become future treatment targets for early RA within the window of opportunity. This may lead to a paradigm shift towards the above described so called ‘remission-induction’ strategies. For this reason it would be interesting to investigate the effectiveness of initiating in early RA more intensive treatment strategies, compared to single csDMARD-initiating strategies according to current guidelines; these more intensive strategies herein are designated remission-induction strategies. The aim of the study is to provide a systematic summary of these remission- induction strategies and their effectiveness. METHODS Systematic literature search and study selection A systematic review of the literature was performed according to current standards and reported according to the Preferred Items for Systematic Reviews and Meta-analyses (PRISMA) statement protocol. 8 In October 2018 we performed a literature search in 2