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

• Published in: Arthritis & rheumatology (Hoboken, N.J.) N.J.), 2022-10, Vol.74 (10), p.1628-1637
• Main Authors: Krause, Dietmar, Mai, Anna, Klaassen‐Mielke, Renate, Timmesfeld, Nina, Trampisch, Ulrike, Rudolf, Henrik, Baraliakos, Xenofon, Schmitz, Elmar, Fendler, Claas, Klink, Claudia, Boeddeker, Stephanie, Saracbasi‐Zender, Ertan, Christoph, Hans‐Joachim, Igelmann, Manfred, Menne, Hans‐Juergen, Schmid, Albert, Rau, Rolf, Wassenberg, Siegfried, Sonuc, Nilüfer, Ose, Claudia, Schade‐Brittinger, Carmen, Trampisch, Hans J., Braun, Juergen
• Format: Article
• Language: English
• Subjects: Active control; Adult; Antirheumatic Agents - adverse effects; Arthritis; Arthritis, Rheumatoid - diagnostic imaging; Arthritis, Rheumatoid - drug therapy; Clinical outcomes; Delayed-Action Preparations; Double-Blind Method; Double-blind studies; Drug Therapy, Combination; Erythrocyte sedimentation rate; Erythrocytes; Glucocorticoids; Glucocorticoids - therapeutic use; Humans; Joint diseases; Methotrexate; Patients; Placebos; Prednisolone; Prednisolone - therapeutic use; Rheumatoid arthritis; Rheumatology; Treatment Outcome
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.42245

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.