Maxime Verhoeven

120 Chapter 6 To analyse if effects of therapy were different for severe and non-severe RA, we first defined subgroups as severe (baseline DAS28>5.1) vs. non-severe (DAS28≤5.1); this classification is based on 1) literature showing that baseline DAS28 is an important prognostic factor for RA severity and 2) the fact that randomisation in U-Act-Early was performed by high (DAS28>5.1) or low disease activity (DAS28≤5.1) enabling a valid subgroup analysis. This resulted in 2 subgroups of n=112 severe and n=114 non-severe patients, allowing analyses, although with limited power. Supplementary Table S2 and S3 provide outcomes of Table 2 in the manuscript, stratified by severe and non-severe RA. Thereafter, we tested for significance the interaction between treatment (TCZ+MTX, TCZ, MTX) and RA severity. For DAS28 and HAQ over 5 years, we used the same model as in the primary analysis. For total SvdH score, we used a zero inflated Poisson regression with total SvdH score as outcome, and treatment, RA severity, and the interaction term treatment*RA severity as covariates, controlling for baseline SvdH score. For DAS28 and HAQ, we found no statistically significant interaction between treatment and RA severity, but for total SvdH score the interaction was statistically significant (p<0.001). The relative rates for radiographic progression were in favour of the TCZ strategy groups in the severe subgroup (TCZ+MTX vs. MTX relative rate (RR) (95% confidence interval) 0.32 (0.19 to 0.53); TCZ vs. MTX 0.38 (0.26 to 0.55)), whereas no significant differences were shown in the non-severe subgroup (TCZ+MTX vs. MTX 1.07 (0.78 to 1.48); TCZ vs. MTX 1.24 (0.87 to 1.78)). This indicates that the joint protective effect of TCZ regimens, in contrast to that of MTX, is slightly stronger in severe RA than in non-severe RA. Supplementary Table S2 Effectiveness outcomes over 5 years, results based on data of patients included in the post-trial follow-up severe RA subgroup, n=112. Mean difference in DAS28 between initial treatment strategy groups over 5 years # Period Strategy comparison Mean difference 95%CI of mean difference Over 5 years TCZ+MTX vs. MTX TCZ vs. MTX TCZ+MTX vs. TCZ - 0.05 - 0.19 0.14 - 0.35 to 0.25 - 0.48 to 0.11 - 0.15 to 0.43 Sustained (drug free) remission over 5 years TCZ+ MTX (n=38) TCZ (n=40) MTX (n=34) P-value Number of patients (%) achieving SR at least once 38 (100) 40 (100) 34 (100) 1.00 1 Cumulative duration of SR in weeks, median (IQR) 186 (118-243) 184 (126-242) 144 (93-202) <0.03 2 Number of patients (%) achieving sDFR at least once 12 (32) 10 (25) 6 (18) 0.40 1 Cumulative duration of sDFR in weeks, median (IQR) 95 (71-154) 139 (53-159) 60 (30-123) 0.26 2