FRI0110 TAPERING TOWARDS DMARD-FREE REMISSION IN ESTABLISHED RHEUMATOID ARTHRITIS: 2 YEAR RESULTS OF THE TARA TRIAL
Authors: E. Van Mulligen, A. Weel, M. Kuijper, J. Hazes, A. Van der Helm - van Mil, P. De Jong
Journal: Annals of the Rheumatic Diseases (2020)

Background: In rheumatoid arthritis (RA) disease outcomes have improved enormously in the last decades. Due to early initiation of therapy, a treat-to-target approach and a growing arsenal of disease-modifying antirheumatic drugs (DMARDs) and biologics, RA patients are in sustained remission more often. This raises the subsequent questions whether treatment should be continued, tapered or stopped. Although DMARD free remission (DFR) is nowadays achievable for increasing numbers of RA patients, the optimal tapering approach still needs to be defined. Objectives: To evaluate the 2-year clinical effectiveness of two gradual tapering strategies, namely tapering the csDMARD first followed by the TNF-inhibitor, or tapering the TNF-inhibitor first followed by the csDMARD. Methods: In this multicenter single-blinded randomised controlled trial RA patients with controlled disease for at least 3 consecutive months, defined as a DAS≤2.4 and a swollen joint count (SJC) ≤1, which was achieved with csDMARDs and a TNF-inhibitor were included. Eligible patients were randomised into gradual tapering csDMARDs followed by the TNF-inhibitor, or vice versa. Medication was tapered in three steps over the course of 6 months. After 12 months, the other DMARD was tapered. Gradual tapering was done by cutting the dosage into half, a quarter and thereafter it was stopped. In case of a flare (DAS44&gt;2.4 or SJC&gt;1) the previous effective dose was restarted and tapering was not initiated any further throughout the whole study period. The primary outcome for the clinical effectiveness was the number of patients with a disease flare, defined as DAS44&gt;2.4 and/or SJC&gt;1. Secondary outcomes were DFR, disease activity, quality of life and functional ability. Outcomes were calculated in an intention-to-treat analysis, using all available data. Results: A total of 189 patients were randomly assigned to tapering the csDMARD first or tapering the TNF-inhibitor first. The cumulative flare rate, after 24 months, for tapering the csDMARD first was 61% (95% CI, 50% - 69%) and for tapering the TNF-inhibitor first was 62% (95% CI, 50%-70%) (p=0.35)(figure 1). The cumulative flare rate differed the most between both groups between 12 and 18 months of follow-up (figure 1). Figure 2 shows an overview of how gradual tapering took place and which medication patients were using at different time points(figure 2). This was indicated for both tapering arms, and for the first and second year (figure 2). For the second year, tapering status was only indicated for the patients who actually tapered medication, so who stayed flare-free in the first year. Patients that tapered their csDMARD first were more often able to completely taper their csDMARD (n=30), and subsequently they also had a higher chance of reaching DFR(n=15) (table 1). However, mean DAS and mean HAQ over time and after 2 years did not differ between both tapering arms (table 1). Table 1. Baseline characteristics and results after 24 months. Tapering csDMARD first (n=94) Tapering TNF-inhibitor first (n=95) Baseline (T0) Age (years), mean (sd ) 55.9 (14.1) 57.2 (10.6) Gender, female, n(% ) 66 (71) 58 (61) Symptom duration (years), median (IQR ) 6.0 (4.3-8.5) 6.3 (4.1-8.9) ACPA positive, n(% ) 61 (72) 65 (75) RF positive, n(% ) 49 (57) 56 (64) 2-year follow-up (T24) Cumulative flare, n(% ) 57 (61) 59 (62) DMARD free remission, n(% ) 15 (16) 8 (8) Tapered, n(% ) 30 (32) 20 (21) DAS, mean (sd ) 1.39 (0.67) 1.30 (0.70) ΔDAS (T24-T0), mean (sd ) 0.41 (0.55) 0.33 (0.77) HAQ-DI, mean (sd ) 0.62 (0.53) 0.52 (0.51) ΔHAQ-DI (T24-T0), mean (sd ) 0.074 (0.40) 0.058 (0.31) Conclusion: The order in which tapering and stopping medication was performed was not superior to each other based on flare rates, DAS and HAQ. However, patients who tapered their csDMARD first could more often completely taper off their medication and, therefore, also reached DFR more often. Disclosure of Interests: None declared