Maxime Verhoeven

133 Cost-effectiveness of treat-to-target strategies over 5 years in PTFU, medication use (per category) during the first 3 months after U-Act-Early (‘first 3 months of PTFU’) were assumed equal to the use in the last 3 months of U-Act-Early and further set as ‘missing’ and imputed for the analysis (see below). To calculate medication costs, medication use was multiplied by national prices, separately for bDMARD, csDMARD, and NSAIDs, see Supplementary Table 1. 12 If the administration route of the medication was intravenous, we calculated additional costs for day care. For NSAIDs, we assumed the most frequently used NSAID in the trial (i.e., naproxen) in a dose of 0.75 gram per day. Other direct healthcare costs and indirect non-healthcare costs Other direct healthcare related resource use (e.g., physician visit, hospital admissions, non RA medication) and indirect non-healthcare related resource use (e.g., travel cost, purchase of a stair lift, etc.) typically over the last 3 months were obtained via healthcare resource use questionnaires, as used in previous studies. 3,4,10,13 Productivity loss costs Data about productivity loss was obtained with the work participation questionnaire as filled out at baseline, 3, 6, 12 and 24 months during the trial, and yearly during PTFU. Costs related to productivity loss were calculated as incidental work loss hours caused by sickness as well as structural reduction in working hours, including discontinuation of paid work. The productivity loss costs related to structural reduction in work were calculated compared to the productivity hours per week at baseline. Working hours lost were valued by the average wage of Dutch citizens by gender to calculate the total productivity loss costs, following the human capital approach. 10 Productivity loss costs were also calculated, applying the friction cost approach using only structural productivity loss hours during the first 15 weeks (i.e., friction period 2017). 10 If the patient reached the retirement age of 65 years, we assumed that patients retired and productivity loss costs no longer occurred. Costs were calculated using 2017 reference prices in euro (€) and in line with the Dutch costing manual see Supplementary Table 1. 10 Discounting Costs were discounted using a discount rate of 4% per year, and QALYs using a discount rate of 1.5% per year, according to Dutch guidelines for economic evaluations in healthcare. 10 Missing data and data imputation To obtain yearly costs and QALYs, linear interpolation was used over scheduled visits within a year. To account for remaining missing cost (12%/22% during trial/PTFU) and QALY 7