Maxime Verhoeven

11 General introduction In the past two decades, several studies have shown that early and more intensive treatment strategies including (combinations of) cs- and bDMARDs, as well as treating to a predefined low level of disease activity, preferably remission, using protocolized step-up treatment (treat-to-target) and regularly monitoring disease activity (tight- control), significantly improve outcomes in RA patients. 2,10 Approximately 30-50% of early RA patients will need more intensive treatment, as they fail to respond sufficiently on MTX-monotherapy (with or without GC bridging). 11 Therefore, several studies tried to predict (in)sufficient response to MTX, however, resulting models are not implemented mainly due to their limited predictive ability. If MTX non-response or toxicity could be reliably predicted, then treatment with the bDMARD tocilizumab (TCZ, interleukin(IL)-6 receptor inhibitor) might be a suitable option for these non-responders since TCZ can be used with lower-dosed MTX, or even without MTX (i.e., TCZ-monotherapy). In contrast to other bDMARDs, like the most tumour necrosis factor inhibitors (TNFi) which are more effective in combination with MTX, no substantial loss in effectiveness is shown for TCZ-monotherapy compared to combination therapy with MTX. 12 Currently, TCZ, like other bDMARDs, is usually not prescribed as first-line treatment, mainly because of cost considerations and, to a lesser extent, safety concerns. 2 In treat-to-target treatment strategies, disease activity is usually monitored by using the disease activity score assessing 28 joints (DAS28) as measuring instrument in the Netherlands. 13 This is a composite measure, consisting of assessment of 28 joints for swelling and tenderness (‘joint counts’; SJC28 and TJC28), an acute phase reactant (APR, e.g., erythrocyte sedimentation rate (ESR)) and patient global assessment (PGA) scored on a visual analogue scale (VAS, PGA-VAS). 1 The assessment of joint counts is rather time consuming, requires a trained healthcare professional and its inter-observer variety often is high. 14 Regularly monitoring disease activity thus is both a key element, and a hurdle in the implementation of treat-to-target strategies in standard care in out- patient-clinics. 15,16 Other validated composite disease activity measures, which could also be used for monitoring disease activity, are the clinical disease activity index (CDAI) and the simplified disease activity index (SDAI). These indices have several similarities compared to DAS28, like an assessment of TJC28 and SJC28 and a PGA-VAS scored by the patient. In addition, an evaluator global assessment VAS scored by evaluator is included in CDAI and SDAI; an APR is included only in SDAI. 17 An instrument to assess disease-modifying effects, specifically for longer-term disease duration, is radiography, to score radiographic progression of joint damage, typically on X-rays of joints of hands, wrists and feet. 18 A relatively newmedical device, using optical spectral transmission (OST) to measure inflammation quickly and objectively in hand and wrist joints, is the HandScan. The HandScan performs a measurement within 5 minutes, without taking time of a 1