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Original Investigation
May 4, 2021

Effect of Half-Dose vs Stable-Dose Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Disease Flares in Patients With Rheumatoid Arthritis in Remission: The ARCTIC REWIND Randomized Clinical Trial

Author Affiliations
  • 1Division of Rheumatology and Research, Diakonhjemmet Hospital, Oslo, Norway
  • 2Clinical Trial Unit, Oslo University Hospital, Oslo, Norway
  • 3Department of Rheumatology, Ålesund Hospital, Helse Møre og Romsdal HF, Ålesund, Norway
  • 4Revmatismesykehuset AS, Lillehammer, Norway
  • 5Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
  • 6Department of Rheumatology, Hospital Østfold HF, Moss, Norway
  • 7Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway
  • 8Department of Rheumatology, Drammen Hospital, Vestre Viken HF, Drammen, Norway
  • 9Department of Rheumatology, Sørlandet Hospital HF, Kristiansand, Norway
  • 10Department of Rheumatology, Helgelandssykehuset Mo i Rana, Mo i Rana, Norway
  • 11Department of Rheumatology, Martina Hansens Hospital, Bærum, Norway
  • 12Faculty of Medicine, University of Oslo, Oslo, Norway
  • 13Division of Rheumatology, Brigham and Women’s Hospital, Boston, Massachusetts
  • 14Department of Rheumatology, Leiden University Medical Centre, Leiden, the Netherlands
JAMA. 2021;325(17):1755-1764. doi:10.1001/jama.2021.4542
Visual Abstract. Effect of Half-Dose vs Stable-Dose csDMARDs on Disease Flares in Patients With Rheumatoid Arthritis in Remission
Effect of Half-Dose vs Stable-Dose csDMARDs on Disease Flares in Patients With Rheumatoid Arthritis in Remission
Key Points

Question  In patients with rheumatoid arthritis in remission taking conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), is reducing the csDMARDs to half dose noninferior to stable csDMARD dosage for the outcome of rheumatoid arthritis flares?

Findings  In this randomized clinical trial that included 160 patients with rheumatoid arthritis in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs resulted in disease flares in 25% vs 6% over 12 months; this did not meet the noninferiority criterion of a 20% difference. There were significantly fewer patients with flares in the stable-dose group.

Meaning  These findings do not support the use of half-dose treatment in patients with rheumatoid arthritis in remission taking csDMARDs.

Abstract

Importance  Sustained remission has become an achievable goal for patients with rheumatoid arthritis (RA) receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), but how to best treat patients in clinical remission remains unclear.

Objective  To assess the effect of tapering of csDMARDs, compared with continuing csDMARDs without tapering, on the risk of flares in patients with RA in sustained remission.

Design, Setting, and Participants  ARCTIC REWIND was a multicenter, randomized, parallel, open-label noninferiority study conducted in 10 Norwegian hospital-based rheumatology practices. A total of 160 patients with RA in remission for 12 months who were receiving stable csDMARD therapy were enrolled between June 2013 and June 2018, and the final visit occurred in June 2019.

Interventions  Patients were randomly assigned to half-dose csDMARDs (n = 80) or stable-dose csDMARDs (n = 80).

Main Outcomes and Measures  The primary end point was the proportion of patients with a disease flare between baseline and the 12-month follow-up, defined as a combination of Disease Activity Score (DAS) greater than 1.6 (threshold for RA remission), an increase in DAS score of 0.6 units or more, and at least 2 swollen joints. A disease flare could also be recorded if both the patient and investigator agreed that a clinically significant flare had occurred. A risk difference of 20% was defined as the noninferiority margin.

Results  Of 160 enrolled patients (mean [SD] age, 55.1 [11.9] years; 66% female), 156 received the allocated therapy, of which 155 without any major protocol violations were included in the primary analysis population (77 receiving half-dose and 78 receiving stable-dose csDMARDs). Flare occurred in 19 patients (25%) in the half-dose csDMARD group compared with 5 (6%) in the stable-dose csDMARD group (risk difference, 18% [95% CI, 7%-29%]). Adverse events occurred in 34 patients (44%) in the half-dose group and 42 (54%) in the stable-dose group, none leading to study discontinuation. No deaths occurred.

Conclusions and Relevance  Among patients with RA in remission taking csDMARD therapy, treatment with half-dose vs stable-dose csDMARDs did not demonstrate noninferiority for the percentage of patients with disease flares over 12 months, and there were significantly fewer flares in the stable-dose group. These findings do not support treatment with half-dose therapy.

Trial Registration  ClinicalTrials.gov Identifier: NCT01881308

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