Maxime Verhoeven

142 Chapter 7 Table 3 (continued) TCZ+MTX= initiation of tocilizumab + methotrexate strategy group; TCZ= initiation of tocilizumab + placebo- methotrexate strategy group; MTX= initiation of methotrexate + placebo-tocilizumab strategy group; Societal perspective= direct healthcare costs + indirect not healthcare costs + productivity loss costs + medication costs; # = using human capital approach; QALY= quality-adjusted life years; ICER= incremental cost effectiveness ratio (using societal perspective according to human capital approach); SE = south east: gain in QALY, less expensive (i.e., TCZ dominant); SW= south west: loss in QALY, less expensive; NW= north west: loss in QALY, more expensive (i.e., TCZ inferior); NE= north east: gain in QALY, more expensive; SC= subcutaneous. DISCUSSION We hypothesized that initiating a TCZ-based strategy using a strict treat-to-target approach and including a clear tapering strategy when in sustained remission might become cost-effective. Our results do not confirm this hypothesis: we found that treat-to- target treatment strategies initiating TCZ as first treatment after diagnosis of RA are not cost-effective compared to a treatment strategy initiating MTX. Our results are in line with those of previous research in which the cost effectiveness of early initiation of bDMARDs compared to MTX initiation was analyzed in early (DMARD-naïve) RA patients. 7 The observed decrease in medication use during U-Act-Early, however, did not decrease further in the PTFU. 9 If a tapering protocol had been included in the PTFU, this might have led to a further decrease in TCZ use and might have increased cost effectiveness of TCZ strategies compared to MTX. Interestingly, our study showed that medication costs did decrease over time but remained higher for TCZ strategies over time, the only exception was the final (5 year) observation where medication cost became lower in both TCZ strategy groups compared to MTX. As specifically in year 5 total medication costs, productivity loss costs and direct healthcare costs are lower in TCZ-based treatment strategies, we hypothesize that this may be due to the fact that these patients need less intensive treatment due to their initial intensive treatment strategy, during the window of opportunity. However, to definitely establish this an evaluation over a longer time horizon would be needed. Furthermore, the differences between TCZ(+MTX) and MTX regarding productivity loss costs were lower than expected. Interestingly, productivity loss costs were saved only in the TCZ group, not in the TCZ+MTX group, compared to MTX. This may indicate that omitting MTX may be an advantage regarding productivity effects of treatment, as MTX is associated with (mild) adverse events. 15 In line with this, also limited saving in overall healthcare costs and indirect non-healthcare costs were made in the TCZ group. We did not include presentism in these costs (i.e., costs of being less productive during working hours) which may have led to a higher impact of productivity on cost savings. However, sensitivity/scenario analyses show that effect would need to be substantial to materially influence the results. Specifically, sensitivity analyses showed that only