OP0220 INITIAL GLUCOCORTICOID BRIDGING IN RHEUMATOID ARTHRITIS: DOES IT AFFECT GLUCOCORTICOID USE OVER TIME?

Abstract

Background Glucocorticoid (GC) ‘bridging’ therapy as temporary part of the initial treatment in rheumatoid arthritis (RA) helps to rapidly suppress disease activity. It has been proposed that patients treated with GC bridging (bridgers) may continue to use more GC later in the disease course than patients who did not receive GC bridging (non-bridgers). Objectives To compare GC use over time between RA patients in clinical trials randomized to treatment with or without initial GC bridging. Methods Data were available from the BeSt, CareRA and COBRA trials, which included study arms with and without initial GC bridging in addition to csDMARD treatment. GC bridging schedules were planned for a minimal duration of 34 (CareRA), 35 (COBRA) and 36 (BeSt) weeks (Table 1). In an individual patient data (IPD) meta-analysis we compared GC use between bridgers and non-bridgers at 12, 18 and 24 months from baseline as primary outcome. Secondary outcomes were the mean cumulative GC dose until 24 months after baseline with and without the bridging period, number of (study defined) flares (DAS28 increase >1.2 or ΔDAS28 >0.6 and ≥3.2 at previous visit), number of DMARD changes (adding a DMARD or switching between DMARDs) and DAS28 over time. We used mixed effects regression analyses including study arm as random effect. To investigate DAS28 over time, an interaction term between treatment group (whether or not started with GC bridging) and time (as categorical variable) was included. Results 252/625 patients (40%) were randomized to GC bridging. Baseline characteristics were comparable between bridgers and non-bridgers. Mean DAS28 improved more rapidly in bridgers in the first 6 months (p<0.01, Figure 1A), but the decrease was similar in both groups thereafter. After the planned end of bridging, GC use was low in both groups (Figure 1B). Only at t=12 months, significantly more bridgers than non-bridgers still or again used GC (OR 3.27 (95% CI 1.06; 10.08)). Disregarding the initial bridging schedules there was no difference between the two groups in cumulative dose, 365 mg (95%CI -62; 793), but the cumulative GC dose including the planned bridging schedules was significantly higher for the bridgers (2889 mg (95% CI 1812; 3967), this can be translated to a difference of 4mg a day for 2 years). The incidence rate ratio (IRR) for (study defined) flares was similar between the groups (IRR 1.14 (95%CI 0.86; 1.50), but the IRR for number of DMARD changes was significantly lower in the bridgers (IRR 0.59 (95%CI 0.38; 0.94)). Conclusion After GC bridging therapy (on average 35 weeks), bridgers had an increased risk of using GC at 12 months from baseline compared to non-bridgers, but not thereafter. The bridging schedule determined the cumulative GC dose over time, which after the bridging period was similar in bridgers and non-bridgers. After the end of bridging schedules there were no differences in mean DAS28, number of flares (by study definition) or post-bridging cumulative GC dose, but bridgers had a more rapid decrease of DAS28 in the first 6 months (during bridging schedule) and fewer DMARD changes over time. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Lotte van Ouwerkerk: None declared, Patrick Verschueren Speakers bureau: consultancy and/or speaker honoraria from AbbVie, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Roularta and Sidekick Health within the last 24 months., Consultant of: consultancy and/or speaker honoraria from AbbVie, Celltrion, Eli Lilly, Galapagos, Gilead, Nordic Pharma, Roularta and Sidekick Health within the last 24 months., Employee of: holds the Pfizer Chair Early Rheumatoid Arthritis Management at KU Leuven, Maarten Boers: None declared, Paul Emery Consultant of: Provided expert advice to Abbvie, Astra-Zeneca, BMS, Boehringer Ingelheim, Galapagos, Gilead, Janssen, MSD, Lilly, Novartis, Pfizer, Roche, Samsung, Grant/research support from: Abbvie, BMS, Lilly, Novartis, Pfizer, Roche, Samsung., Pascal de Jong: None declared, Robert B.M. Landewé: None declared, WIllem Lems Consultant of: Received consultancy speaker fees from Eli Lilly, Pfizer, Amgen, Galapagos and UCB., Grant/research support from: received study grants from Pfizer, Josef Smolen: None declared, Thomas Huizinga: None declared, Cornelia Allaart Grant/research support from: received study grants for BeSt study and IMPROVED study from Centocor (now Janssen) and AbbVie, respectively. Grants were for conducting the clinical trials., Sytske Anne Bergstra Grant/research support from: Received an ASPIRE grant from Pfizer.

Authors 11

1. Lotte van Ouwerkerk Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center (LUMC), Rheumatology, Leiden, Netherlands

2. Patrick Verschueren

   KU Leuven

   Affiliation as printed

   KU Leuven, Skeletal Biology and Engineering Research Center, Leuven, Belgium

3. Maarten Boers

   Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, locatie VUmc, Rheumatology, Amsterdam, Netherlands

4. Paul E. Emery
   Affiliation as printed

   Leeds NIHR Biomedical Research Centre, Rheumatology, Leeds, United Kingdom

5. Pascal H P de Jong

   Erasmus MC

   Affiliation as printed

   Erasmus Medical Center, Rheumatology, Rotterdam, Netherlands

6. Robert Landewé

   Zuyderland Medisch Centrum

   Affiliation as printed

   Zuyderland Medical Center Heerlen, Rheumatology, Heerlen, Netherlands

7. Willem F. Lems

   Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam

   Affiliation as printed

   Amsterdam UMC, locatie VUmc, Rheumatology, Amsterdam, Netherlands

8. Josef S Smolen

   Medical University of Vienna

   Affiliation as printed

   Medical University of Vienna, Rheumatology, Wien, Austria

9. Tom W. J. Huizinga Aachen

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center (LUMC), Rheumatology, Leiden, Netherlands

10. Cornelia F Allaart Aachen

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center (LUMC), Rheumatology, Leiden, Netherlands

11. Sytske Anne Bergstra Aachen

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center (LUMC), Rheumatology, Leiden, Netherlands