POS0514 Long-term use of glucocorticoids in people with rheumatoid arthritis: a Cochrane living systematic review

Background: Despite advancements in the management of rheumatoid arthritis (RA) with disease-modifying antirheumatic drugs (DMARDs), glucocorticoids (GCs) remain widely used. Concerns about the adverse effects of long-term GC use create uncertainty regarding their optimal role in RA management. Objectives: To assess the benefits and harms of long-term GC therapy (defined as use longer than six months) in adults with RA. Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL Ovid), MEDLINE Ovid and Embase Ovid combining standard Cochrane search filters for ‘rheumatoid arthritis' and ‘randomised trial', and a search of the US National Institutes of Health Ongoing Trials Register (www.clinicaltrials.gov) and the World Health Organization International Clinical Trials Registry Platform (apps.who.int/trialsearch), using the search term ‘rheumatoid arthritis'. For assessments of adverse effects, we searched US Food and Drug Administration – MedWatch, European Medicines Evaluation Agency, Australian Adverse Drug Reaction Bulletin, and Medicines and Healthcare products Regulatory Agency (MHRA), as recommended by the Cochrane Musculoskeletal Group. We searched all databases from their inception to June 2024 with no restriction on language of publication. As this is a living systematic review we will search for new trials on a 6-monthly basis and will update the evidence as new trials are identified. We included trials comparing the use of oral or intramuscular GCs versus placebo in combination with the same DMARD therapy. Key outcomes included proportion achieving low disease activity, mean pain, mean function, mean disease activity, mean radiographic progression, adverse events potentially associated with GCs use and withdrawals due to adverse events. Two authors independently screened search results, extracted data, and assessed risk of bias and certainty of the evidence using standard Cochrane and GRADE methodology, respectively. Results: We identified six trials involving 1,263 participants. At 12 months, GCs may make little to no difference in the proportion of patients achieving low disease activity (RR 1.23, 95% CI 0.79 to 1.91; low certainty evidence due to serious imprecision and serious indirectness). Similarly, GCs probably make little to no difference to pain (MD -3.81, 95% CI -7.01 to -0.61 on a 0 to 100 scale, effect size smaller than MCID 11.9; moderate certainty evidence due to serious indirectness) or function (MD -0.13, 95% CI -0.21 to -0.06 on a 0 to 3 scale, effect size smaller than MCID 0.22; moderate certainty evidence due to serious indirectness). GC therapy probably results in a small improvement in mean disease activity (MD -0.36, 95% CI -0.68 to -0.05 on a 0 to 9.3 scale; moderate certainty evidence due to serious indirectness). Assessed at last follow-up (24 months), GC therapy probably results in a small reduction in mean radiographic progression (MD -19.7, 95% CI -37.7 to -1.67, assessed with Sharp/van der Heijde score 0 to 448; moderate certainty evidence due to serious indirectness). At 24 months follow-up, GC therapy may increase the risk of GC-specific adverse events (RR 1.67, 95% CI 1.01 to 2.76; low certainty evidence due to very serious imprecision - very small event rate, less than 100 events per group) but may have little or no effect on withdrawals due to adverse events (RR 0.87, 95% CI 0.67 to 1.14; low certainty evidence due to very serious imprecision - very small event rate, less than 100 events per group) (Table 1). Conclusion: In adults with RA receiving DMARD therapy, long-term use (up to 24 months) of GC probably provides some improvement in pain, physical function, and disease activity and may reduce radiographic progression. However, on average these benefits are likely to be of little clinical significance and may be counterbalanced by an increased risk of GC-specific adverse events. Current evidence, of low to moderate certainty, suggests that routine long-term GC use in RA cannot be recommended due to the modest benefits and potential harms. Decision-making regarding long-term GC use should consider individual patient circumstances and prioritize shared decision-making. REFERENCES: NIL . Table 1Summary of Findings table: GC + DMARD vs GC placebo + DMARD for adults with rheumatoid arthritis.OutcomesAnticipated absolute effects* (95% CI)Relative effect(95% CI)№ of participants(studies)Certainty of the evidence(GRADE)Risk with GC placebo + DMARDRisk with GC + DMARDProportion of participants with low disease activity assessed with: DAS28 ≤ 3.2Follow-up: 12 months349 per 1000429 per 1000(276 to 666)RR 1.23(0.79 to 1.91)687(2 RCTs)⊕⊕⊝⊝LowPain score assessed with: VAS Scale from: 0 to 100; lower betterFollow-up: range 6 months to 12 monthsThe mean pain score was 40MD 3.81 (7.01 lower to 0.61 lower)-949(5 RCTs)⊕⊕⊕⊝ModerateFunction score assessed with: HAQ Scale from: 0 to 3; lower betterFollow-up: range 6 months to 12 monthsThe mean function score was 1.1MD 0.13 (0.21 lower to 0.06 lower)-949(5 RCTs)⊕⊕⊕⊝ModerateRadiographic progression assessed with: Sharp/van der Heijde (SvHD) score from: 0 to 448; lower betterFollow-up: 24 monthsThe mean radiographic progression (SvHD score) was 19.1MD 19.7 (37.7 lower to 1.67 lower)-870(6 RCTs)⊕⊕⊕⊝ModerateAdverse events of special interest (adverse events potentially associated with GC use; see adverse event domains in the OMERACT endorsed core set for glucocorticoid impact)Follow-up: 24 months89 per 1000149 per 1000(90 to 247)RR 1.67(1.01 to 2.76)1024(5 RCTs)⊕⊕⊝⊝LowWithdrawal due to any adverse eventFollow-up: 24 months153 per 1000133 per 1000(103 to 175)RR 0.87(0.67 to 1.14)1260(6 RCTs)⊕⊕⊝⊝LowMD - mean difference, VAS - visual analogue scale, RR - relative risk Acknowledgements: NIL . Disclosure of Interests: None declared . © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.

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