Maxime Verhoeven

225 Summary and general discussion to develop and validate a composite disease activity measure for assessing RA patients using OST values obtained by the HandScan instead of the clinical joint assessment (SJC/TJC; chapter 10 ). The developed formula for the new disease activity index, DAS- OST, was: -0.44 + OST*0.03 + male*-0.11 + LN(ESR)*0.77 + VAS*0.03. The intra-class correlation coefficient, evaluating agreement between DAS-OST and DAS28, was high in the internal and external validation cohort. Diagnostic performance of DAS-OST for discriminating specific disease activity states was in general good as well. As there exists no gold standard for measuring disease activity in RA patients, we used DAS28 as reference standard for the development of DAS-OST, described above. Another reference standard relevant for clinical practice, because it would indicate the need for intensifying of the therapeutic strategy or not, would be the assessment whether RA is active or inactive, according to the rheumatologist. Therefore, chapter 11 aimed to establish the value of DAS-OST, versus that of DAS28, to classify RA as active versus inactive, with the rheumatologist’s clinical classification as reference standard. In our analyses, DAS-OST showed a clearly better performance than a single OST-score, but statistically significantly less compared to DAS28. The final chapter, chapter 12 , of part II of this thesis is a letter in response to a paper of Triantafyllias et al. 7 Our letter aimed to explain the gender difference in OST-score observed by Triantafyllias et al. as observed also in our studies. We concluded that the OST-score in controls and probably also in RA patients is statistically significantly higher in males compared to in females, although there is considerable overlap in OST-scores between subgroups. GENERAL DISCUSSION What is the optimal DMARD treatment strategy for DMARD-naïve early RA patients? The finding that the additional effectiveness of more intensive treatment strategies (i.e., using bDMARDs as initial treatment) is limited compared to single csDMARD strategies when combined with GCs is relevant for clinical practice as bDMARDs are not available in all countries, mainly due to their high costs. 8 It is reassuring that csDMARD therapy with GC as bridging therapy and as additional DMARD when used over a longer-term might be effective and safe, 9 and probably a more cost-effective alternative. Also the longer- term effectiveness (of main importance in a chronic disease like RA) of initiating more intensive treatment strategies compared to a strategy starting with MTX-monotherapy in early RA does not seem to do better. 10 This is likely due to the treat-to-target design with swift treatment intensification in case of insufficient effect of initial therapy. 2 In line with this it is plausible that the specific initial DMARD therapy used is not the most important, but treating patients within the ‘window of opportunity’ to rapidly suppress disease activity is. 11 13