OP0318 TREATMENT TAPERING AND WITHDRAWAL IN RHEUMATOID ARTHRITIS WITH STABLE REMISSION - FINAL ANALYSIS OF THE RETRO STUDY

Abstract

Background:Due to better treatment strategies and higher remission rates the management of rheumatoid arthritis (RA) patients in sustained remission is of increasing interest (1). The Rheumatoid Arthritis in Ongoing Remission (RETRO) study investigated the possibility to taper and stop disease modifying anti-rheumatic drugs (DMARDs).Objectives:To compare one-year remission and relapse rates in rheumatoid arthritis patients randomized to continued treatment, reduced treatment or gradual treatment withdrawal after stable remission under routine care.Methods:Primary data of the phase III, randomized, controlled RETRO trial in RA patients with stable conventional synthetic and/or biologic DMARD treatment in sustained (>6 months) DAS28-ESR remission (<2.6 units). Patients were randomized 1:1:1 into three strategy arms (continuation of 100% DMARD dose, CONT; tapering to 50% DMARD dose, TAP; 50% tapering followed by withdrawal of DMARDs, STOP). The primary endpoint was the proportion of patients in sustained DAS28-ESR remission after 1 year.Results:316 RA patients in sustained remission were included, 303 were randomized (CONT: N=100; TAP: N=102; STOP: N=101) and 282 (93%) had complete data sets after 1 year (CONT:N=93; TAP: N=93; STOP: N=96; Table 1). After 1 year, 81.2%, 58.6%, 43.3% of patients, maintained their remission state over 1 year in the CONT, TAP and STOP arms, respectively (p=0.0004 with log rank test for trend; Figure 1). Hazard ratios for flare were 3.02 (95%CI 1.69 to 5.40) and 4.34 (95%CI 2.48 to 7.60) for the TAP and STOP arms. RA patients who flared were more likely to be female, have longer disease duration, RF/ACPA positivity and higher baseline DAS-28 scores with standardized mean differences >0.2. Serious adverse events were reported in 10.8%, 7.5%, and 13.5% in the CONT, TAP and STOP arms, respectively.Table 1.Baseline CharacteristicsGroupControlReduceReduce/StopOverallN939396282Age, mean(SD)55.9 (12.7)56.9 (13.0)56.5 (13.3)56.5 (13.0)Female, n (%)53 (57.0)57 (62.0)57 (59.4)167 (59.4)RF, n (%)52 (55.9)58 (62.4)52 (54.2)162 (57.4)ACPA, n (%)53 (57.0)50 (54.9)55 (57.3)158 (56.4)Disease duration, years, mean(SD)7.6 (6.9)7.8 (6.9)6.8 (8.1)7.4 (7.3)Remission duration, months, mean(SD)20.6 (18.0)16.5 (15.9)22.7 (30.4)20.0 (22.6)Biologics, n (%)39 (41.9)44 (47.3)39 (40.6)122 (43.3)Methotrexate, n (%)71 (76.3)67 (72.0)75 (78.1)213 (75.5)Other DMARDs, n (%)24 (25.8)20 (21.5)16 (16.7)60 (21.3)Glucocorticoids, n (%)27 (29.0)23 (24.7)17 (17.7)67 (23.8)CRP, mg/L, mean(SD)0.3 (0.3)0.5 (0.5)0.5 (0.6)0.4 (0.5)ESR, mm/h, mean(SD)11.3 (8.4)12.2 (8.8)13.0 (10.0)12.2 (9.1)Tender joint count, mean(SD)0.2 (0.6)0.0 (0.2)0.1 (0.3)0.1 (0.4)Swollen joint count, mean(SD)0.1 (0.3)0.1 (0.3)0.1 (0.4)0.1 (0.3)Physician VAS,mm, mean(SD)1.8 (4.2)2.6 (4.4)2.0 (3.9)2.1 (4.2)Patient VAS,mm, mean(SD)6.4 (9.0)5.5 (8.3)4.5 (8.4)5.5 (8.6)HAQ, standard, mean(SD)0.2 (0.4)0.2 (0.3)0.2 (0.4)0.2 (0.4)HAQ, alternative, mean(SD)0.2 (0.4)0.1 (0.3)0.2 (0.3)0.2 (0.3)DAS-28, mean(SD)1.7 (0.7)1.7 (0.6)1.7 (0.6)1.7 (0.6)SDAI, mean(SD)1.4 (1.5)1.4 (1.5)1.3 (1.3)1.3 (1.4)DAS-28 remission, n (%)91 (97.8)93 (100.0)95 (99.0)279 (98.9)SDAI remission, n (%)79 (87.8)79 (84.9)88 (92.6)246 (88.5)Boolean remission, n (%)69 (75.8)71 (76.3)76 (79.2)216 (77.1)Conclusion:This randomized controlled study shows that half of RA patients in sustained remission relapse when tapering/stopping their DMARDs. Presence of autoantibodies, higher baseline DAS28-ESR and female sex are predictors for flares.