Maxime Verhoeven

131 Cost-effectiveness of treat-to-target strategies over 5 years INTRODUCTION Rheumatoid arthritis (RA) is a chronic inflammatory disease of mainly the joints, in which lifelong treatment is required to reduce symptoms, improve physical function, and avoid structural joint damage. Over the last decades, early treatment with disease modifying anti-rheumatic drugs (DMARDs) according to the treat-to-target principle together with the use of newer, more effective, biological (b)DMARDs improved these outcomes. 1 Due to their high costs compared to conventional synthetic (cs)DMARDs, bDMARDs are reserved as second-line treatment after a first DMARD (mostly methotrexate (MTX)) has shown to be insufficiently effective. Typically, bDMARDs are added to the existing csDMARD therapy. Some studies have evaluated TNF-inhibitors (TNFi) as initial bDMARD therapy in RA, and have shown that initial treatment with this bDMARD, though effective, is currently not cost-effective over 1-2 years. 2–4 Simulation model based analyses over a longer term (i.e., 5-year to life-time horizon) also conclude that this is not a cost- effective strategy. 5–7 Tocilizumab (TCZ) is a non-TNFi bDMARD, targeting the IL-6 receptor. A recent trial and its post-trial follow-up (PTFU) investigated the effect of TCZ as first-line treatment, in early RA patients. U-Act-Early was a 2-year multicentre, double-blind, randomized, placebo-controlled trial in early (DMARD-naïve) RA patients treated to the target of remission (i.e., DAS28<2.6 with ≤4 swollen joints). Patients were assigned to step- up treatment strategies starting with TCZ, MTX or their combination (TCZ+MTX). 8 If the treatment target was not achieved, MTX (in TCZ-monotherapy group) or TCZ (in MTX group) was added. When patients achieved and remained in remission for ≥24 weeks, medication was tapered and finally stopped. 8 Patients were followed for 3 years after the trial (i.e., PTFU), during which treatment was at the discretion of the treating rheumatologist. 9 Results of U-Act-Early and its PTFU showed a high effectiveness of all treatment strategies. Almost all patients achieved (sustained) remission over follow-up, which was achieved earlier in the TCZ strategy groups. Due to active tapering during the trial, we observed that bDMARD use decreased in TCZ-based strategies and increased in the MTX-based strategy, and TCZ use was almost similar in both arms after two years. High effectiveness and higher sustained (drug free) remission rates compared to previous cost effectiveness bDMARD-studies were achieved in U-Act-Early, as well as in its PTFU, possibly due to the patient population with very early RA, treated within the ‘window of opportunity’. Furthermore, TCZ-monotherapy was equally effective as TCZ+MTX as initial strategy, 9 in contrast to most TNFi. Since some patients do not tolerate MTX, TCZ-monotherapy may have a positive influence on quality of life and productivity. Therefore, the question could be raised whether using TCZ (+/- MTX) as initial therapy in a strict treat-to-target strategy with active tapering in case of sustained remission 7