Maxime Verhoeven

48 Chapter 3 to 0.97]), but not over 24 months, Supplementary Figure S1b. No statistically significant differences were found between the TCZ arms and the MTX+Pred arm for any safety outcome, Table 2. Results for all primary and secondary outcomes are shown in Table 2, Figure 1 and, Supplementary Figure S1-S2. Table 2 Differences in effectiveness and safety outcomes over 24 and 3 months between TCZ strategy arms and MTX+Pred strategy arm. TCZ+MTX vs. MTX+Pred p-value TCZ vs. MTX+Pred p-value Effectiveness DAS28, mean difference (95%CI) - Over 24 months - Over first 3 months -0.62 (-1.14 to -0.10) -0.44 (-1.00 to 0.13) 0.02 0.14 -0.44 (-1.00 to 0.12) -0.37 (-0.98 to 0.24) 0.13 0.24 m-CDAI, proportional mean difference (95% CI) 1 - Over 24 months - Over first 3 months 0.10 (-0.16 to 0.36) 0.25 ( 0.02 to 0.48) 0.47 0.04 0.24 (-0.04 to 0.52) 0.35 ( 0.11 to 0.59) 0.09 0.01 DAS28 remission, RR (95%CI) - Over 24 months - Over first 3 months 1.11 ( 1.02 to 1.22) 1.12 ( 1.02 to 1.22) 0.02 0.03 1.09 ( 1.00 to 1.20) 1.11 ( 1.01 to 1.22) 0.05 0.04 m-CDAI remission, RR (95%CI) - Over 24 months - Over first 3 months 0.96 ( 0.84 to 1.08) 0.90 ( 0.81 to 0.99) 0.52 0.03 0.90 ( 0.78 to 1.02) 0.88 ( 0.89 to 0.97) 0.12 0.01 ConRew score, mean difference (95%CI) 3.92 (-1.12 to 8.97) 0.14 4.73 (-0.41 to 9.86) 0.08 HAQ score, mean difference (95%CI) 0.01 (-0.14 to 0.17) 0.86 0.09 (-0.07 to 0.25) 0.29 SvdH score, IRR (95%CI) 0.70 ( 0.32 to 1.57) 0.40 1.05 ( 0.48 to 2.29) 0.89 Safety Occurrence of ≥1x elevated ALT, RR (95%CI) 1.62 ( 0.66 to 3.97) 0.30 0.92 ( 0.33 to 2.53) 0.86 Occurrence of ≥1x elevated AST, RR (95%CI) 1.48 ( 0.35 to 6.17) 0.60 0.55 ( 0.11 to 2.86) 0.48 Occurrence of ≥1 infection, RR (95%CI) 0.99 ( 0.11 to 9.03) 0.97 1.05 ( 0.11 to 9.58) 0.96 Drop out due to AE, RR (95%CI) 1.18 ( 0.39 to 3.63) 0.77 1.30 ( 0.43 to 3.90) 0.65 Random effects for the variables in the model were evaluated and retained if the model fit was improved, as judged by a decrease in Bayesian information criterion or a change in one of the estimates of treatment effect of at least 10%. Random effects for the following variables were used in the models: DAS28, HAQ, RF-status, smoking status, all at baseline and time. Negative values indicate lower values for continuous outcomes (i.e., DAS28, m-CDAI, HAQ) in TCZ strategy arms compared to the MTX+Pred strategy arm. (I)RR >1 indicates higher occurrence of the outcome (i.e., DAS28 remission, m-CDAI remission, drop out due to AE) in TCZ strategy arms compared to the MTX+Pred strategy arm. 1 log transformed values. Multiplying the above regression coefficients by 100 leads to a difference on a modified percentage scale. 16