Maxime Verhoeven

107 Effectiveness and safety of treat-to-target strategies over 5 years Outcomes The primary end point was DAS28 over 5 years. The secondary end point was medication use (NSAID use, GCs, csDMARDs and bDMARDs) during the 3-year PTFU. Other secondary end points were number of patients achieving SR and sDFR, cumulative duration of SR and sDFR, change in SvdH score, HAQ scores, and the number of patients with occurrence of any AE, or SAE, all variables evaluated over 5 years. Statistics Data of all patients enrolled in this PTFUwere used for analyses. Continuous variables were described using means with standard deviations (SD) or medians with interquartile ranges (IQR), where appropriate. Frequencies and proportions were calculated for categorical variables. Differences between the initial strategy groups in baseline characteristics were evaluated and tested using one-way ANOVA for continuous outcomes and chi-square test or Fisher’s exact test for categorical outcomes. Mixed model analyses were used to assess differences over time between the initial treatment strategy groups in continuous outcomes, with a random intercept and fixed effects for treatment arm, visit-week, the interaction visit-week*treatment arm, correcting for DAS28 at baseline and center (i.e., both the stratification factors used for randomization). Differences between the initial treatment strategy groups in proportions of patients using medication were tested with a Cochran-Mantel-Haenszel (CMH) test. Differences between the initial treatment strategy groups in proportions of patients achieving SR and sDFR and cumulative duration of all SR and sDFR periods in individual patients were tested with CMH test and linear regression analysis, respectively, correcting for baseline DAS28 (for CMH; DAS28 <5.1 or ≥5.1, as this cut-off was used for the randomization) and center. Differences between the initial treatment strategy groups in median change in radiographic scores were tested with the van Elteren test, correcting for baseline DAS28 and center. The statistical analyses were performed in SAS version 9.4 and R version 3.4.3. All tests were two-sided; a p-value ≤0.05 was considered statistically significant. Sensitivity analysis To evaluate the generalizability of our findings, a sensitivity analysis was performed for the primary end point, including also patients (n= 91) who had not participated in the PTFU, only in the 2-year U-Act-Early trial. Missing data for all patients in DAS28 and swollen joint count (SJC)28 over time were imputed using a joint multivariate model of 2-level data. The package “jomo” in R was used for multiple imputation; this package also handles categorical data and uses cluster-specific covariance matrices. 11 The variables treatment arm, visit-week, duration of participation, reason for drop out, and DAS28, HAQ, age, disease duration, gender and rheumatoid factor (RF) status (positive/negative) at baseline were used in the imputation model. Patient was used 6