Maxime Verhoeven

42 Chapter 3 ABSTRACT Objective Methotrexate (MTX), often combined with low-moderately dosed prednisone, is still the cornerstone of initial treatment for early RA. It is not known how this strategy compares with initial treatment with a biological. We therefore compared the effectiveness of tocilizumab (TCZ), or TCZ plus MTX (TCZ+MTX) with MTX plus 10mg prednisone (MTX+Pred), all initiated within a treat-to-target treatment strategy in early RA. Methods Using individual patient data of 2 trials, we indirectly compared tight-controlled treat- to-target strategies initiating TCZ (n=103), TCZ+MTX (n=106) or MTX+Pred (n=117), using initiation of MTX (n=227) as reference. Primary outcome was DAS28 over 24 months. To assess the influence of acute phase reactants (APRs), a disease activity composite outcome score without APR (i.e., m-CDAI) was analysed. Secondary outcomes were remission (several definitions), physical function and radiographic progression. Multi- level models were used to account for clustering within trials and patients over time, correcting for relevant confounders. Results DAS28 over 24 months was lower for TCZ+MTX than for MTX+Pred (mean difference: -0.62 [95%CI -1.14 to -0.10]). Remission was more often achieved in TCZ+MTX and in TCZ vs. MTX+Pred (p=0.02/ 0.05, respectively). Excluding APRs from the disease activity outcome score, TCZ-based strategies showed a slightly higher m-CDAI compared to MTX+Pred, but this was not statistically significant. Other outcomes were also not statistically significantly different between the strategies. Conclusion In early RA patients, although TCZ-based strategies resulted in better DAS28 and remission rates compared to MTX+Pred, at least part of these effects may be due to a specific effect of TCZ on APRs.