Maxime Verhoeven

44 Chapter 3 the MTX+Pred arm was more effective regarding achieving remission and inhibition of erosive joint damage than the MTX arm, with a numerically better safety profile. 6 We hypothesised that TCZ-based treatment strategies in early RA patients would be more effective than a MTX+Pred-based treatment strategy, and would have similar safety. Therefore, we indirectly compared the effectiveness and safety of initial treatment strategies based on TCZ, with or without MTX, with those of an initial strategy based on MTX with 10mg prednisone, using individual patient data from the U-Act-Early and CAMERA-II trials. METHODS Patients U-Act-Early and CAMERA-II were 2-year, double-blind, placebo-controlled randomized controlled trials in DMARD-naïve early RA patients. Patients who participated (1) fulfilled the 1987 American College of Rheumatology (ACR) criteria (CAMERA-II), or (for U-Act- Early) 2010 ACR/European League Against Rheumatism (EULAR) classification criteria, (2) had a disease duration <12 months and (3) had active disease (in U-Act-Early defined as disease activity score assessing 28 joints (DAS28) ≥2.6; not specified in CAMERA-II) at baseline. In both trials, treatment followed a tight-control, treat-to-target strategy, aiming for (sustained) remission. In U-Act-Early remission was defined as DAS28 <2.6 and ≤4 swollen joints on the 28 swollen joint count (SJC28). In CAMERA-II remission was defined as absence of swollen joints and at least 2 of the following: tender joint count (TJC) ≤3, patient visual analogue score (VAS) of general health ≤20 mm, erythrocyte sedimentation rate (ESR) ≤20 mm/h. In U-Act-Early, patients were randomized to a treatment strategy initiating oral MTX (starting dose 10mg/week), intravenous TCZ (8mg/kg every 4 weeks) or their combination (TCZ+MTX). In CAMERA-II, patients were randomized to a treatment strategy initiating oral MTX (starting dose 10mg/week) with or without 10mg prednisone (MTX+Pred) daily. In both trials, the MTX dose was increased in steps of 5mg, up to 30mg per week or up to the maximum tolerable dose until remission was achieved. In U-Act-Early when the treatment target was not achieved, placebo was replaced by the respective active treatment in the combination strategy arms initiating MTX or TCZ plus placebo, and in both trials, if the treatment target was still not achieved, a tumour necrosis factor inhibitor was started. More detailed information on the individual trials has been reported previously. 6,12