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.

Initial glucocorticoid bridging in rheumatoid arthritis: does it affect glucocorticoid use over time?

“…Trying to avoid adverse effects of GC could affect achieving the benefits of GC. The recent CORRA trial showed that after a ‘COBRA light schedule’ that tapered to zero in 3 months, no radiological benefit could be shown 34. For now, it remains unclear which is the best bridging schedule when balancing both safety and efficacy, and which (cumulative) dose of GC gives an increased risk of adverse events.…”

Three Months of Glucocorticoids in Rheumatoid Arthritis: A Bridge Too Short?

“…In this issue of Arthritis & Rheumatology , Krause et al describe a large placebo‐controlled trial examining the potential benefit of short‐term GC bridge therapy on structural damage in RA (14). The study was adequately powered for a difference of 2 Sharp/van der Heijde units and was meticulously conducted, but it was unable to show benefit of up to ~1,400 mg oral prednisolone over 12 weeks.…”

Correlation of Hematological Indices and Acute-Phase Reactants in Rheumatoid Arthritis Patients on Disease-Modifying Antirheumatic Drugs: A Retrospective Cohort Analysis

“…The severity of RA varies, and treatment typically involves the use of one or a combination of immunomodulators, commonly referred to as disease-modifying anti-rheumatic drugs (DMARDs) [1]. Acute-phase reactant data, particularly regarding the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and the disease activity score 28 (DAS28), are crucial in predicting prognosis and guiding treatment [2][3][4][5]. Disease activity indices are also pivotal in assessing the effectiveness of treatments in clinical trials.…”