OP0318 TREATMENT TAPERING AND WITHDRAWAL IN RHEUMATOID ARTHRITIS WITH STABLE REMISSION - FINAL ANALYSIS OF THE RETRO STUDY
Authors: Hagen M. , Tascilar K. , Reiser M. , Valor L. , Haschka J. , Kleyer A. , Hueber A. , Manger B. , Cobra J. , Figuereido C. , Finzel S. , Tony H. P. , Wendler J. , Kleinert S. , Schuch F. , Ronneberger M. , Feuchtenberger M. , Fleck M. , Manger K. , Ochs W. , Schmitt-Haendle M. , Lorenz H. M. , Alten R. , Henes J. , Krueger K. , Rech J. , Schett G. 
Published: May 2021

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 Characteristics

GroupControlReduceReduce/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.

References:

[1]Schett G et al. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions. Ann Rheum Dis. 2016 Aug;75(8):1428-37.

Disclosure of Interests:

Melanie Hagen Speakers bureau: advisory boards, Koray Tascilar Speakers bureau: advisory board, Michaela Reiser: None declared, Larissa Valor: None declared, Judith Haschka Speakers bureau: advisory board, Arnd Kleyer Speakers bureau: advisory board, Axel Hueber Speakers bureau: advisory boards, Bernhard Manger Speakers bureau: advisory boards, Jayme Cobra Speakers bureau: advisory boards, Camille Figuereido Speakers bureau: advisory boards, Stephanie Finzel Speakers bureau: advisory boards, Hans-Peter Tony Speakers bureau: advisory boards, Joerg Wendler Speakers bureau: advisory boards, Stefan Kleinert Speakers bureau: advisory boards, Florian Schuch Speakers bureau: advisory boards, Monika Ronneberger: None declared, Martin Feuchtenberger Speakers bureau: advisory boards, Martin Fleck Speakers bureau: advisory boards, Karin Manger: None declared, Wolfgang Ochs: None declared, Matthias Schmitt-Haendle: None declared, Hanns-Martin Lorenz Speakers bureau: advisory boards, Rieke Alten Speakers bureau: advisory boards, Jörg Henes Speakers bureau: advisory boards, Klaus Krueger Speakers bureau: advisory boards, Jürgen Rech Speakers bureau: advisory boards, Georg Schett Speakers bureau: advisory boards.