Maxime Verhoeven

132 Chapter 7 might be cost-effective in very early RA patients compared to MTX as initial strategy, taking into account costs related to medical consumption, other direct healthcare costs, indirect non-healthcare costs, as well as costs related to productivity loss. The current study aimed to compare these costs and quality-adjusted life years (QALYs), as a generic measure of effectiveness, of initial treatment with TCZ+MTX, TCZ and MTX in a treat-to-target treatment strategy over the 5-year observation period. METHODS Detailed methods of U-Act-Early and PTFU are reported elsewhere. 8,9 In the current study we evaluated the cost effectiveness of TCZ(+MTX) compared to MTX. For this purpose we used individual patient data of U-Act-Early and its PTFU, hence we performed a trial-based cost-utility analysis (i.e., using empirical study data). Patients visited the out-patient-clinic every month during the 2-year trial period, every 3 months during the first year of the PTFU and every 6 months thereafter. The medical ethics research committee of the University Medical Center Utrecht approved the trial, ID number: ML28388. For the PTFU, the institutional review boards of the participating centers confirmed that the Medical Research Involving Human Subjects Act (WMO) was not applicable. In both studies, all patients gave written informed consent. QALYs Effectiveness was expressed as QALYs, measured at baseline, 3, 6, 12 and 24 months using the EuroQol 5-Dimensions 5-Levels (EQ-5D5L) with results expressed as a utility score. Utility is a score ranging from 0 (death) to 1 (full health), and was based on the Dutch tariff. 10 For the post-trial period, during which EQ-5D5L was not measured, and in case of missing EQ-5D5L data, utility was estimated from HAQ and age. 11 See Supplementary Data S1 for details. Medication costs Medication use was based on recorded dose and duration of (non-placebo) MTX and TCZ, and recorded use (yes/no) for NSAIDs. If patients dropped out during U-Act-Early (about 25%, n=80), we assumed that TCZ was discontinued, treatment with MTX (15mg per week) was continued and a TNFi (i.e., adalimumab 40mg subcutaneously biweekly) was added until the end of the trial, as advised by the U-Act-Early study protocol. If the reason for drop-out was infection or malignancy (about 34% of dropouts, n=27), we assumed that treatment was continued with MTX (15mg per week), and that, for safety reasons, another csDMARD (e.g., sulfasalazine 1000mg twice a day) was added, instead of a TNFi, in line with the U-Act-Early protocol and clinical guidelines during the inclusion period (i.e., 2010-2012). For patients completing U-Act-Early, but not included