Maxime Verhoeven

223 Summary and general discussion of the Clinical Disease Activity Index (CDAI) as outcome, no difference in efficacy between TCZ-based strategies and MTX with prednisone could be detected. An explanation could be the known direct acute phase suppression by TCZ, extra lowering DAS28. As it is known that, approximately 30% of the patients does not benefit from MTX 1 or does not tolerate it, identifying these patients up-front would be useful for a more patient-tailored treatment strategy. A prediction model (including baseline predictors; DAS28, HAQ, erythrocyte folate, genetic markers (SNPs; ABCB1 and ABCC3), smoking and BMI) for insufficient clinical response to MTX at three months of treatment (i.e., DAS28>3.2) was previously developed. 4 We performed an (external) validation of this prediction model using data from the trial arm initiating MTX-monotherapy in U-Act-Early (chapter 4) . Results showed a similar predictive value in this validation cohort as in the development cohort. Investigation of the specific predictive effect of individual components in the model showed baseline DAS28>5.1 and HAQ>0.6 to be the strongest predictors. Lifestyle parameters (BMI/smoking) and erythrocyte folate further increased the predictive value. Whether this prediction model is strong enough at patient level remains to be established. An important outcome of RA is joint damage, as typically scored on X-rays (‘radiographic progression’). Although it is generally found for disease activity outcomes that TCZ-monotherapy and TCZ combination therapy with MTX are equally effective, 5 their relative effect on preventing radiographic progression is not clear. Chapter 5 aimed to address this by combining data of several clinical trials. We explored the effect of TCZ strategies on different components of radiographic progression, and whether the level of disease activity, joint damage present at baseline and disease duration modified this relative effect. Results indicated that combination therapy with MTX (TCZ+MTX) is more effective in preventing radiographic progression compared to TCZ-monotherapy, but that the joint-sparing effectiveness of TCZ-monotherapy might approximate that of TCZ+MTX in specific subgroups. Specifically, in early RA patients with more joint damage or a lower DAS28 at baseline, and in established RA patients with longer disease duration. As the impact of a treatment strategy for a chronic disease like RA becomes more apparent over a longer-term, participants of U-Act-Early 1 were followed for three additional years in an extension study. During this period, treatment was according to standard of care. The aim of chapter 6 was to determine the longer-term effectiveness in daily clinical practice of the initial treatment strategies used in U-Act-Early. Although 1 U-Act-Early was a 2-year, randomized placebo controlled, double-blind trial, in which DMARD-naïve early RA patients were treated to the target of sustained remission. Patients were randomly assigned to a treatment strategy initiating TCZ, MTX or their combination. If the treatment target was not achieved, MTX (in TCZ-monotherapy group) or TCZ (in MTX group) was added. When patients achieved sustained remission (i.e., remission for ≥24 weeks) medication was tapered, and finally stopped. 13