Maxime Verhoeven

43 An indirect comparison of treat-to-target strategies in early RA INTRODUCTION Rheumatoid arthritis (RA) is a chronic inflammatory joint disease often requiring lifelong treatment to reduce symptoms, improve physical function, and avoid structural joint damage. Implementation of treat-to-target treatment strategies has improved those outcomes. Guidelines recommend to start a conventional synthetic (cs) disease modifying anti-rheumatic drug (DMARD) as soon as the diagnosis is made and to swiftly adjust treatment when the treatment target is not achieved. 1 Methotrexate (MTX) is typically the initial treatment, often combined with glucocorticoids (GCs). MTX is well- tolerated, effective and inexpensive. GCs have been used for 70 years in RA and have proven to be effective and safe, if used in low-moderate dose. 2–5 Combination treatment of csDMARDs with GCs improves disease control, physical function and radiographic progression. 6–8 Similar beneficial effects have been shown for treatment with biological (b)DMARDs. 1 Earlier performed studies showed that first-line treatment initiating MTX was less effective compared to treatments initiating bDMARDs, importantly for example for achieving drug free remission (DFR). 9 However, a bDMARD is typically not prescribed as first-line treatment, mainly because of cost considerations and to a lesser extent safety concerns. For this reason several studies attempted to predict bDMARD response on individual patient level, which proved not to be feasible so far. 10 However, with tapering of originator bDMARDs and increasing number of less costly biosimilar approvals, these may in the future be more frequently considered as an initial treatment option in RA, as this may increasingly become more cost-effective. Therefore, it is important to better understand the relative effectiveness and safety of a first-line treatment strategy initiating a bDMARD compared to initiating a csDMARD with GCs. This is particularly important as the long-term impact of a potent treatment strategy might be more pronounced when started in early disease (i.e., within the window of opportunity). 11 Our department has previously performed the U-Act-Early and the second Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA-II) trials in early DMARD-naïve RA patients. In U-Act-Early the effectiveness and safety of treat- to-target treatment strategies initiating the bDMARD tocilizumab (TCZ) with MTX (TCZ+MTX) or with placebo (TCZ) were compared with those of a strategy initiating MTX with placebo (MTX). 12 Following the rationale that with longer-term use GCs act as a DMARD, in CAMERA-II effectiveness of a treat-to-target treatment strategy initiating MTX with 10mg prednisone (MTX+Pred) was compared with that of a strategy initiating MTX with placebo (MTX). 6 The MTX strategies in both trials were similar. The U-Act-Early trial concluded that the TCZ strategy arms were more effective in achieving sustained remission (i.e., remission ≥24 weeks) and showed less erosive joint damage than the MTX strategy arm, with a similar safety profile. 12 The CAMERA-II trial concluded that 3