A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS INTO THE SUCCESS RATE OF GLUCOCORTICOID DISCONTINUATION AFTER THEIR USE AS INITIAL BRIDGING THERAPY IN RHEUMATOID ARTHRITIS PATIENTS IN OBSERVATIONAL COHORTS AND CLINICAL TRIALS

Background: Glucocorticoids (GC) are widely used for the initial treatment of rheumatoid arthritis (RA), to induce rapid suppression of inflammation and clinical symptoms and thereby limit radiographic damage progression. There are concerns that GC use in the long term is associated with a dose and duration dependent risk of serious side effects. Therefore, international guidelines have recommended to start GC when initiating a csDMARD, but to discontinue GC as rapidly as clinically feasible, preferably within 3 months (bridging therapy). In contrast, due to the concerns of GC side effects, the ACR guidelines published in 2021 conditionally recommend to start csDMARD monotherapy without GC bridging therapy. Objectives: We aim to evaluate the success rate of GC discontinuation after using temporary GC as part of initial therapy (‘bridging’) both in observational cohorts and clinical trials in newly diagnosed RA patients. Methods: Systematic literature searches were conducted to identify observational cohorts (scoping search) and clinical trials (in-depth search) that included RA patients who were treated with initial GC bridging therapy. GC bridging was defined as oral or intramuscular GC treatment that was discontinued within one year, alongside conventional DMARD therapy. Patient percentages still or again using GC were considered to represent the reverse of successful discontinuation. Random-effects meta-analyses were performed stratified by time point. Results: The literature search on observational cohort studies could not identify any study answering the research question, since it remained unclear which patients had received GC as part of the initial treatment. The literature search for clinical trials identified 7160 abstracts, resulting in 10 included studies, with varying type and dose of GC and varying tapering schedules ( Table 1 ). Of these included studies, 4 reported sufficient data on GC discontinuation or GC use after the bridging phase. The pooled proportion of patients who were still using GC was 22% (95% Confidence Interval (CI) 8; 37, based on 4 trials) at 12 months and 10% at 24 months (95% CI -1; 22, based on 2 trials) (Figure 1). Thus, the vast majority had stopped GC. Heterogeneity was substantial (I ≥ 65%). Table 1. Overview of included clinical trials. Study (publication year) Tapering schedule (mg/day) COBRA (1997) In 7 weeks to 7.5. Stop after 28 weeks.* BeSt (2005) In 7 weeks to 7.5. Stop in 8 weeks after week 28 if DAS persistently ≤2.4 IDEA (2014) N.A. COBRA-light (2015) arm 1: in 7 weeks to 7.5 arm 2: in 9 weeks to 7.5 Stop after 32 weeks if DAS<1.6. IMPROVED (2014) In 7 weeks to 7.5. Stop after 20 weeks if DAS <1.6 at 4 months. ARCTIC (2016) In 7 weeks to 0 if DAS <1.6 and no swollen joints present. tREACH (2013) In 10 weeks to 0.* CareRA (2017) - in 7 weeks to 7.5, further tapered from week 28, stop after 34 weeks. - Classic - in 6 weeks to 5, further tapered from week 28, stop after 34 weeks. - Slim - in 6 weeks to 5, further tapered from week 28, stop after 34 weeks. - Avant garde All if DAS28(CRP) ≤3.2. Hua et al. (2020) Tapering after 4 months to 5, stop after 6 months.* NORD-STAR (2020) - arm 1A (oral prednisolone ) In 9 weeks to 5. Stop after 9 months.* DAS=disease activity score; mg=milligram; N.A.=not applicable. *GC tapered and stopped according to protocol, not depending on disease activity score. Conclusion: The success rate of GC discontinuation after bridging as part of initial treatment of RA has been described in a limited number of studies. Reports on observational cohorts did not answer the research question and in clinical trials reports, GC (dis)continuation data were also scarce. However, the available data show that GC can be discontinued successfully in a large majority of patients. The paucity of data also reveals that more efforts are needed to provide data towards identifying the optimal GC bridging and discontinuation strategy, combining Treatment to Target with Starting to Stop. Acknowledgements: We would like to thank J.W. Schoones for his help and expertise in the systematic literature search. Disclosure of Interests: Lotte van Ouwerkerk: None declared, Andriko Palmowski: None declared, Isabell Nevins: None declared, Frank Buttgereit Consultant of: Consultant of AstraZeneca, AbbVie, Grünenthal, Horizon Pharma, Pfizer, and Roche., Grant/research support from: Grant/research support from AbbVie, Horizon Pharma, Pfizer, and Roche., Patrick Verschueren Consultant of: Was consultant for ABBVIE, BMS, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Pfizer and UCB., Employee of: Holds the Pfizer Chair Early Rheumatoid Arthritis Management at KU Leuven., Josef Smolen: None declared, Robert B.M. Landewé Shareholder of: Shareholder of: Director of Rheumatology Consultancy BV., Consultant of: Consultant of: Honoraria from AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Eli-Lilly, Novartis, Pfizer, UCB Pharma., Hans Bijlsma Consultant of: Consultant for Galapagos, Lilly and Sun., Grant/research support from: Received study grants from AbbVie and Roche., Andreas Kerschbaumer: None declared, Rene Westhovens Consultant of: Was consultant for Celltrion, Galapagos and Gilead., Thomas Huizinga: None declared, Cornelia Allaart Grant/research support from: Received study grants for BeSt and IMPROVED from Centocor Inc. (now Janssen) and AbbVie, respectively., Sytske Anne Bergstra Grant/research support from: Received an ASPIRE grant from Pfizer. Citation: , volume 81, supplement 1, year 2022, page 1329Session: Rheumatoid arthritis - non biologic treatment and small molecules (Publication Only)