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Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP
  1. Merete Lund Hetland1,
  2. Mikkel Østergaard1,
  3. Bo Ejbjerg2,
  4. Søren Jacobsen3,
  5. Kristian Stengaard-Pedersen4,
  6. Peter Junker5,
  7. Tine Lottenburger6,
  8. Ib Hansen4,
  9. Lis Smedegaard Andersen7,
  10. Ulrik Tarp4,
  11. Anders Svendsen6,
  12. Jens Kristian Pedersen7,
  13. Henrik Skjødt1,
  14. Torkell Ellingsen4,
  15. Hanne Lindegaard5,
  16. Jan Pødenphant8,
  17. Kim Hørslev-Petersen7,
  18. CIMESTRA study group
  1. 1Department of Rheumatology, Glostrup Hospital, Glostrup, Denmark
  2. 2Department of Rheumatology, Slagelse Hospital, Slagelse, Denmark
  3. 3Department of Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
  4. 4Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark
  5. 5Department of Rheumatology, Odense University Hospital, Odense, Denmark
  6. 6Department of Rheumatology, Vejle Hospital, Denmark
  7. 7Department of Rheumatology, Rheumatism Hospital, University of Southern Denmark, Gråsten, Denmark
  8. 8Department of Rheumatology, Copenhagen University Hospital, Gentofte, Denmark
  1. Correspondence to Kim Hørslev-Petersen, Rheumatisk Hospital, University of Southern Denmark, Toldbodgade 3, DK-6300 Gråsten, Denmark; horslev{at}


Objective To investigate the short-term and long-term efficacy of intra-articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthritis (RA).

Methods During 2 years of follow-up in the CIMESTRA trial, 160 patients received intra-articular betamethasone in up to four swollen joints/visit in combination with disease-modifying antirheumatic drugs. Short-term efficacy was assessed by EULAR good response. Long-term efficacy by Kaplan–Meier plots of the joint injection survival (ie, the time between injection and renewed flare). Potential predictors of joint injection survival were tested.

Results 1373 Unique joints (ankles, elbows, knees, metacarpophalangeal (MCP), metatarsophalangeal, proximal interphalangeal (PIP), shoulders, wrists) were injected during 2 years. 531 Joints received a second injection, and 262 a third. At baseline, the median numbers of injections (dose of betamethasone) was 4 (28 mg), declining to 0 (0 mg) at subsequent visits. At weeks 2, 4 and 6, 50.0%, 58.1% and 61.7% had achieved a EULAR good response. After 1 and 2 years, respectively, 62.3% (95% CI 58.1% to 66.9%) and 55.5% (51.1% to 60.3%) of the joints injected at baseline had not relapsed. All joint areas had good 2-year joint injection survival, longest for the PIP joints: 73.7% (79.4% to 95.3%). 2-Year joint injection survival was higher for first injections: 56.6% (53.7% to 59.8%) than for the second: 43.4% (38.4% to 49.0%) and the third: 31.3% (25.0% to 39.3%). Adverse events were mild and transient. A high MRI synovitis score of MCP joints and anti-CCP-negativity were associated with poorer joint injection survival, whereas IgM-RF and C-reactive protein were not.

Conclusion In early RA, intra-articular injections of betamethasone in small and large peripheral joints resulted in rapid, effective and longlasting inflammatory control. The cumulative dose of betamethasone was low, and the injections were well tolerated.

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  • Funding The study was supported by a grant from the Danish Rheumatism Association, Novartis Healthcare Denmark A/S provided ciclosporin and placebo-ciclosporin and sponsored an independent good clinical practice monitor. Nycomed provided methotrexate, folic acid and calcium/vitamin D. Schering-Plough provided injectable betamethasone. Merck Sharp & Dohme provided alendronate. The sponsors were not involved in the study set-up, data collection, analysis or interpretation, and had no influence on the publishing of data.

  • Competing interests None.

  • Ethics approval Ethics committees in all five participating counties.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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