Maxime Verhoeven

196 Chapter 10 DISCUSSION We developed and validated three disease activity indices using OST. DAS-OST(JC) performed similarly as DAS-OST, and therefore we prefer DAS-OST as this index has the most simple formula. DAS-OST without patient VAS performed significantly less well. In general, the (diagnostic) performance was found to be good and results remained well in the external validation (ACURA) cohort including patients with a more active disease compared to the out-patient-clinic patients of the MMC cohort. The measurement error of DAS28 is generally assumed to be around 0.6, 12,13 in the validation cohorts similar and slightly higher measurement errors between DAS28 and DAS-OST were found. 12,13 Misclassification occurred in both cohorts, but mainly regarding the low- and moderate disease activity categories and less regarding remission and high disease activity states, see Supplementary Table S2 and S3. Diagnostic performance of DAS-OST for defining specific disease activity states was in general good, although specifically sensitivity for HDA was low, indicating that the performance in ruling out HDA using this index might be suboptimal (compared to DAS28, the reference). However, the primary use would be intensification of treatment strategy in absence of remission and/or LDA, and thus diagnostic accuracy for these outcomes are most important. Sensitivity and specificity for remission and LDA were adequate. Therefore we assume that our disease activity index, DAS-OST, might save the rheumatologists’ time regarding evaluation of the disease activity of their patients in clinical practice. Interestingly, in our analyses sensitivity and especially specificity were low when using Boolean remission as outcome for DAS-OST. Therefore, we calculated sensitivity and specificity for DAS28 itself to detect Boolean remission (data not shown). In this analysis sensitivity and specificity were also low(er) and similar with those of DAS-OST (87% and 68%, respectively). A limitation of this study is the lack of information on smoking status as it is known that smoking decreases the blood flow of digits, which could influence the HandScan score. 6 Furthermore, data on BMI and/or hand-size, which have been found to affect the HandScan outcome, 14 was absent. By including gender in our models, we may have partly corrected for the effect of hand size, which was found to influence the OST- score independently from the disease activity variables in DAS-OST, but it would be interesting to investigate whether hand size or BMI would have an additional effect. Despite these limitations, the current study containing information of 1505 unique RA patients (with multiple observations) and an external validation cohort provided a unique opportunity to develop and validate a disease activity index using the HandScan. The fact that these were data of daily clinical practice of unselected patients enhances generalisability of results.