The Efficacy of Short-Term Bridging Strategies With High- and Low-Dose Prednisolone on Radiographic and Clinical Outcomes in Active Early Rheumatoid Arthritis: A Double-Blind, Randomized, Placebo-Controlled Trial

Abstract

Objective: In active early rheumatoid arthritis (RA), glucocorticoids are often used for bridging, due to the delayed action of methotrexate. This study was undertaken to compare the effect of 3 bridging strategies, including high-dose and low-dose prednisolone, on radiographic and clinical outcomes.

Methods: Adult RA patients from 1 rheumatology hospital and 23 rheumatology practices who presented with moderate/high disease activity were randomized (1:1:1) to receive 60 mg prednisolone (high-dose prednisolone [HDP]) or 10 mg prednisolone (low-dose prednisolone [LDP]) daily (tapered to 0 mg within 12 weeks) or placebo. The 12-week intervention period was followed by 40 weeks of therapy at the physicians' discretion. The primary outcome measure was radiographic change at 1 year measured using the total modified Sharp/van der Heijde score (SHS). Disease activity was assessed with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR).

Results: Of 395 randomized patients (HDP, n = 132; LDP, n = 131; placebo, n = 132), 375 (95%) remained in the modified intention-to-treat analysis. Mean ± SD changes in SHS scores in the 3 groups after 1 year were comparable: mean ± SD 1.0 ± 2.0 units in the HDP group, 1.1 ± 2.2 units in the LDP group, and 1.1 ± 1.5 units in the placebo group. The primary analysis showed no superiority of HDP compared to placebo (estimated difference of the mean change -0.04 [95% confidence interval (95% CI) -0.5, 0.4]). At week 12, the mean DAS28-ESR differed: -0.6 (95% CI -1.0, -0.2) for HDP versus placebo; -0.8 (95% CI -1.2, -0.5) for LDP versus placebo. At week 52, there was no significant difference in DAS28-ESR between the 3 groups (range 2.6-2.8). Serious adverse events occurred similarly often.

Conclusion: Short-term glucocorticoid bridging therapy at a high dose showed no benefit with regard to progression of radiographic damage at 1 year.