Thu0475 the efficacy of oral glucocorticosteroids for pain in rheumatoid arthritis: a preliminary report of a meta-analysis

Background:Glucocorticosteroids (GCs) are used to provide rapid relief of symptoms in people with active RA. Their use is recommended by most RA management guidelines and systematic reviews, although the magnitude of their benefit above placebo is uncertain. Persistent pain remains a problem in RA, even despite optimal immunomodulatory management. Systemic GC use may be associated with important adverse events.Objectives:To quantify the specific effects of oral GCs for RA pain.Methods:A systematic literature review was performed for RCTs using GCs in RA compared to inactive treatment. Trials were included whether or not participants received DMARD treatments, so long as a specific effect could be assigned to GCs. Medline, Embase and Cochrane databases were searched until November 2019 and 2 reviewers independently assessed titles, abstracts and full texts. Data for pain were synthesized in a meta-analysis. This study is part of a wider review (PROSPERO CRD42019111562).For subgroup analyses, follow up time points of 0-3 months, >3 - 6 months and >6 months were selected to address duration of effect. Individual studies could contribute to each of the 3 follow up subgroups.Meta-analysis was performed on standardized mean differences (SMDs, bodily pain data) and mean differences (MDs, 100mm VASpain only) of change from baseline (sd), using the Meta and Metafor packages in R. Heterogeneity was quantified using I2and tau statistics. Bias was assessed with a funnel plot and Eggers test.Results:15983 papers, 470 abstracts and 152 full texts were assessed. Pain data from 12 RCTs were suitable for the meta-analyses. The most common pain metric was the 100mm VASpain (9 trials).Study populations ranged from n=12 to n=350 participants, 50% to 71% were female with mean ages from 43 to 66 years. Baseline scores for VASpain ranged from to 34 to 66 mm. Means were reported for DAS28 (from 4.9 to 5.8), ESR (25 to 60mm) and CRP (5 to 27mg/L).Data synthesis at the reported primary time point/end point showed a statistically significant reduction in bodily pain in participants treated with GCs; SMD = -0.36 (10 studies, 1377 participants, 95% CI, -0.59 to -0.14, p=0.002) with significant heterogeneity (I2= 66%, tau = 0.27, p<0.01). The Funnel plot suggested asymmetry, favouring GCs (Eggers p = 0.007).Subgroup analyses were used to investigate the time course of specific effects on pain. Efficacy displayed time-related decreases after initiation. From 0-3 months SMD= -0.56 (95% CI, -0.76 to -0.36, p<0.001, 9 studies, 936 participants, I2= 43%, Eggers p= 0.002). Efficacy was lower at >3 - 6 months (SMD= -0.32, 95%CI -0.52 to -0.11, p=0.002, 3 studies, 382 participants, I2=0%, Eggers p=0.75) and further reduced at >6 months (SMD= -0.07, 95%CI, -0.23 to 0.08, p=0.357, 4 studies, 665 participants, I2= 7%, Eggers p=0.43).For trial data collected during concomitant oral GC dosage, mean difference (MDs) in 100mm VASpain was -14mm (95% CI, -20mm to -9mm) greater improvement in GC than control in the 0-3 month period (8 studies, 1047 participants, I2= 70%). For later follow ups, MDs at >3 to 6 months were -6mm (95% CI, -11mm to -1mm, 3 studies, 537 participants), and -1mm (95% CI, -6mm to 4mm, 3 studies, 369 participants) at >6 months.Conclusion:Oral GCs have efficacy for pain in RA but the mean effect is of borderline clinical importance, and greatest shortly after steroids are commenced. GCs were usually used alongside other treatments as part of a combination. Future research might determine who might gain most benefit from systemic GCs, and improve other treatments to reduce the burden of pain.Acknowledgments:Dr Douglas Grindley for help devising search strategyDisclosure of Interests: :Daniel McWilliams Grant/research support from: Grant support from Pfizer Ltd, Divya Thankaraj: None declared, Rheinallt Morgan: None declared, Julie Jones-Diette: None declared, David Walsh Grant/research support from: Grant support from Pfizer Ltd and Eli Lilly, Consultant of: Consultancy to Eli Lilly, Pfizer, Abbvie and GSK (all payments made to University of Nottingham). Consultancy to Love Productions(all payments made to the University of Nottingham).