Maxime Verhoeven

114 Chapter 6 Subgroup analyses for (non-) severe RA are shown in Supplementary files (Table S2 and S3). In general, results are in line with the overall results, probably except for total SvdH score. Safety No statistically significant differences over 5 years were found in safety outcomes between strategy groups as initially randomized, Table 3. Of the patients in the TCZ+MTX initiation strategy group, 21 (28%) experienced at least one SAE compared with 23 (29%) in the TCZ initiation strategy group and 15 (21%) in the MTX initiation strategy group, p=0.47. Infections, benign/malignant neoplasms and cardiac disorders were the most common SAEs and occurred at least once 15, 8 and 8 times, respectively. Occurrence of at least one serious infection was numerically more frequent in the TCZ initiation strategy groups compared with the MTX initiation strategy group (7 in TCZ+MTX, 5 in TCZ vs. 1 in MTX), p=0.11. Table 3 Safety outcomes over 5 years, results based on data of patients included in the post-trial follow-up, n=226. TCZ+MTX (n=75) TCZ (n=79) MTX (n=72) P-value 1 ≥1 AE, n (%) 75 (100) 78 (99) 72 (100) 1.00 AE rate per 100 patient-years 336 340.96 382 Treatment was given for AE, % 73 70 72 0.13 ≥1 SAE, n (%) 21 (28) 23 (29) 15 (21) 0.47 SAE rate per 100 patient-years 7.1 10.5 6.5 ≥1 serious infection, n (%) 7 (9) 5 (6) 1 (1) 0.11 1 = extended Fisher exact test TCZ+MTX= tocilizumab + methotrexate initiation strategy group; TCZ= tocilizumab + placebo-methotrexate initiation strategy group; MTX= methotrexate + placebo-tocilizumab initiation strategy group; AE= adverse event; SAE= serious adverse event. Sensitivity analysis For the primary end point, DAS28 over 5 years, the results of the sensitivity analysis using data of all patients who were included in U-Act-Early (n=317), after imputation of missing PTFU data, were in line with the findings of our main analysis with DAS28 as end point, see Supplementary Table S5. The sensitivity analysis, analysing the individual unweighted components of the DAS28 separately (ESR excluded), to eliminate the influence of TCZ on APR in the primary outcome yielded statistically significant differences between the treatment strategies for U-Act-Early trial period, but not for the PTFU, see Supplementary Table S3.