Flare risk after oral glucocorticoid bridging with methotrexate or intra-articular bridging with triple therapy in early rheumatoid arthritis

J Intern Med. 2026 Jun;299(6):741-753. doi: 10.1111/joim.70094. Epub 2026 Apr 6.

Abstract

Objectives: To investigate, in early rheumatoid arthritis, whether bridging with glucocorticoids (GCs) is associated with an increased risk of flare following GC tapering and withdrawal.

Methods: A total of 810 NOrdic Rheumatic Diseases Strategy Trials And Registries (NORD-STAR) patients were included in this post hoc analysis: all received methotrexate (MTX), in addition to which 135 patients received oral GC bridging therapy ('oral GC group'); 80 received intra-articular (IA) GC bridging therapy, sulfasalazine and hydroxychloroquine ('injection GC group'); and 595 received one of three (certolizumab pegol, abatacept and tocilizumab) biologic disease-modifying antirheumatic drugs (bDMARDs), hereafter the ('bDMARD group'). Clinical disease activity index (CDAI) flares (≥4.5 increase in CDAI score) were assessed longitudinally.

Results: Up to 48 weeks, flare occurred at least once in 43% of oral GC, 24% of injection GC and 28% of bDMARD patients. Over-time relative risk (RR) was higher with oral GC bridging (adjusted RR, 1.54; 95% CI, 1.16-2.03) but similar with injection GC bridging (adjusted RR 0.93; 95% CI, 0.54-1.55) versus bDMARD. Flare rates were numerically higher in the oral GC versus bDMARD group at all time points (12, 24, 32, 40 and 48 weeks), with a significant difference at w.40, the visit after protocol-defined GC discontinuation; at this visit 27% of patients who discontinued GC experienced flare; 29% among those in remission; 33% remained on low-dose prednisolone at 48 weeks.

Conclusion: Discontinuation of oral GC bridging therapy on background MTX is associated with increased flare risk, even among patients in remission. Flare rates with IA GC bridging plus triple therapy did not differ from the bDMARD group.

Trial registration number: EudraCT 2011-004720-35; ClinicalTrials.gov NCT01491815.

Keywords: flare; intra‐articular glucocorticoid injections; oral glucocorticoids; rheumatoid arthritis; tapering and discontinuation.

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antirheumatic Agents* / administration & dosage
  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Rheumatoid* / drug therapy
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids* / administration & dosage
  • Glucocorticoids* / adverse effects
  • Glucocorticoids* / therapeutic use
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Injections, Intra-Articular
  • Male
  • Methotrexate* / administration & dosage
  • Methotrexate* / therapeutic use
  • Middle Aged
  • Sulfasalazine / administration & dosage
  • Symptom Flare Up

Substances

  • Methotrexate
  • Glucocorticoids
  • Antirheumatic Agents
  • Hydroxychloroquine
  • Sulfasalazine

Associated data

  • ClinicalTrials.gov/NCT01491815