Background: Sustained remission is the goal of rheumatoid arthritis (RA) care, and more patients reach and maintain this state on conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with treat-to-target strategies. The knowledge about whether csDMARDs can be tapered in RA remission is limited.
Objectives: The primary objective of the study was to assess the effect of tapering of csDMARDs on the risk of flares in RA patients in sustained clinical remission.
Methods: In the open, phase 4, non-inferiority ARCTIC REWIND trial, RA patients in clinical remission for ≥ 12 months on stable csDMARD therapy were randomised to continued stable csDMARD or half dose csDMARD. Patients had to be in DAS remission at inclusion with no swollen joints (of 44). The primary endpoint was the proportion of patients with a disease flare during 12 months (defined as a combination of DAS >1.6, change in DAS >0.6 and ≥2 swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Patients attended visits every 4 months, with extra visits in case of flares. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. Mixed effect logistic regression was used to test the inferiority null-hypothesis in the per-protocol population. Radiographs at 0 and 12 months were scored by van der Heijde Sharp score (average score of two readers, progression: ≥1 unit change/year). Clinicaltrials.gov NCT01881308.
Results: We enrolled 160 patients, 155 received the allocated treatment strategy. Baseline characteristics were overall well balanced (Table). 78% of patients in the stable csDMARD arm and 84% in the half-dose csDMARD arm used methotrexate monotherapy. In the primary analysis, we observed flares in 6% of patients on stable csDMARD, compared to 25% in the half-dose csDMARD arm, giving a risk difference (95% CI) of 18.3% (7.2% to 29.3%, Fig 1). Non-inferiority could not be claimed, with the results showing superiority of the stable arm over the half-dose arm (Fig 1). Similar results were found in methotrexate monotherapy users. In the stable arm, 2/5 (40%) escalated DMARD medication following the flares, compared to 18/19 (95%) in the tapering arm. No progression of radiographic joint damage was observed in 79.5% of patients on stable DMARDs and 62.7% of those tapering, difference (95% CI) -17.7% (-33.0%, -2.3%, Fig 2E). At 12 months, 92% of patients in the stable and 85% of patients in the tapered arm were in DAS remission (Fig 2C). The frequency of adverse events was 75 in the stable arm and 53 in the tapered arm, with serious adverse events in 2 (2.6%) of patients in the stable and 4 (5.1%, including two serious infections) patients in the tapered arm.
Conclusion: In RA patients in sustained remission on csDMARDs, continued csDMARD therapy with stable dosage led to significantly fewer disease activity flares and less frequent radiographic joint damage progression than tapered csDMARD treatment.
Disclosure of Interests: Siri Lillegraven: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga: None declared, Joe Sexton: None declared, Inge Olsen: None declared, Hallvard Fremstad: None declared, Cristina Spada: None declared, Tor Magne Madland: None declared, Christian A. Høili Consultant of: Novartis, Gunnstein Bakland Consultant of: Novartis, UCB, Åse Lexberg: None declared, Inger Johanne Widding Hansen: None declared, Inger M. Hansen: None declared, Hilde Haukeland Consultant of: Novartis, Maud-Kristine A Ljosa: None declared, Ellen Moholt: None declared, Till Uhlig Consultant of: Lilly, Pfizer, Speakers bureau: Grünenthal, Novartis, Daniel Solomon Grant/research support from: Funding from Abbvie and Amgen unrelated to this work, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Tore K. Kvien Grant/research support from: Received grants from Abbvie, Hospira/Pfizer, MSD and Roche (not relevant for this abstract)., Consultant of: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Paid instructor for: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Speakers bureau: Have received personal fees from Abbvie, Biogen, BMS, Celltrion, Eli Lily, Hospira/Pfizer, MSD, Novartis, Orion Pharma, Roche, Sandoz, UCB, Sanofi and Mylan (not relevant for this abstract)., Espen A Haavardsholm Grant/research support from: AbbVie, UCB Pharma, Pfizer Inc, MSD Norway, Roche Norway, Consultant of: Pfizer, AbbVie, Janssen-Cilag, Gilead, UCB Pharma, Celgene, Lilly, Paid instructor for: UCB Pharma, Speakers bureau: Pfizer, AbbVie, UCB Pharma, Celgene, Lilly, Roche, MSD
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