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OP0019 STABLE VERSUS TAPERED AND WITHDRAWN TREATMENT WITH TUMOR NECROSIS FACTOR INHIBITOR IN RHEUMATOID ARTHRITIS REMISSION (ARCTIC REWIND): A RANDOMISED, OPEN-LABEL, PHASE 4, NON-INFERIORITY TRIAL
  1. S. Lillegraven1,
  2. N. P. Sundlisæter1,
  3. A. B. Aga1,
  4. J. Sexton1,
  5. I. Olsen2,
  6. Å. Lexberg3,
  7. T. M. Madland4,
  8. H. Fremstad5,
  9. C. A. Høili6,
  10. G. Bakland7,
  11. C. Spada8,
  12. H. Haukeland9,
  13. I. M. Hansen10,
  14. E. Moholt1,
  15. T. Uhlig1,
  16. D. Solomon11,
  17. D. Van der Heijde1,12,
  18. T. K. Kvien1,
  19. E. A. Haavardsholm1
  1. 1Diakonhjemmet Hospital, Oslo, Norway
  2. 2Oslo Univ. Hosp., Oslo, Norway
  3. 3Vestre Viken HF, Drammen, Norway
  4. 4Haukeland Univ. Hosp., Bergen, Norway
  5. 5Ålesund Hosp., Ålesund, Norway
  6. 6Hosp. Østfold, Moss, Norway
  7. 7Univ. Hosp. of N. Norway, Tromsø, Norway
  8. 8Revmatismesykehuset, Lillehammer, Norway
  9. 9Martina Hansens Hosp., Bærum, Norway
  10. 10Helgelandssykehuset, Mo i Rana, Norway
  11. 11Brigham and Women’s Hosp., Boston, United States of America
  12. 12Leiden Univ., Leiden, Netherlands

Abstract

Background: Remission is the preferred treatment target in rheumatoid arthritis (RA), and many patients require biologic DMARDs to reach this state. It is debated whether tapering of tumor necrosis factor inhibitor (TNFi) treatment to discontinuation should be considered in RA patients who sustain remission on treatment (1).

Objectives: The primary study objective was to assess the effect of tapering and withdrawal of TNFi on the risk of flares in RA patients in clinical remission.

Methods: In the non-inferiority ARCTIC REWIND trial, RA patients in remission for at least 12 months on stable TNFi therapy were randomly assigned to continued stable TNFi or tapering (half-dose TNFi for 4 months, thereafter withdrawal of TNFi), with visits every four months. csDMARD co-medication was kept stable in both arms. Patients had to be in DAS remission at inclusion with 0/44 swollen joints. The primary endpoint was the proportion of patients with disease flare during the 12-month study period (defined as DAS>1.6, change in DAS>0.6 and 2 or more swollen joints, or the physician and patient agreed that a clinically significant flare had occurred). Full-dose TNFi was reinstated in case of flares in the tapering arm. The non-inferiority margin was 20%, with a predefined superiority test if non-inferiority was not shown. The inferiority null-hypothesis was tested in the per-protocol population by mixed effect logistic regression. Radiographs were scored by van der Heijde modified Sharp score (0 and 12 months, average of two readers, progression: ≥1 unit change). Clinicaltrials NCT01881308.

Results: We randomised 99 patients, 92 received the allocated treatment strategy, 84 were included in the per-protocol population. Baseline characteristics, clinical and ultrasound disease activity were balanced (Table). csDMARD co-medication was used by 93% in the stable and 88% in the tapering arm. In the primary analysis, 5% of patients in the stable TNFi arm experienced a flare during 12 months, compared to 63% in the tapering TNFi arm. The risk difference (95% CI) was 58% (42% to 74%, Fig 1), with stable treatment being deemed superior to tapering. 90% in the stable and 81% in the tapering arm did not show progression of radiographic joint damage, difference (95% CI) -9% (-24%, 6%). At 12 months, DAS scores, DAS remission and function were similar between groups (Fig 2). The numbers of adverse events (AE)/serious AE in the stable and tapering arm were 57/2 and 50/3, respectively, with 26 and 15 infections.

Conclusion: In a randomised clinical trial assessing patients in prolonged and deep RA remission, we observed a large increase in the flare rate in patients who tapered and discontinued TNFi. Patients responded well to reinstated treatment and remission rates in the two study arms were comparable at 12 months.

References: [1]Smolen et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. ARD 2020

Table 1.

Baseline values – n (%), mean (SD), or median (IQR)

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, Åse Lexberg: None declared, Tor Magne Madland: None declared, Hallvard Fremstad: None declared, Christian A. Høili Consultant of: Novartis, Gunnstein Bakland Consultant of: Novartis, UCB, Cristina Spada: None declared, Hilde Haukeland Consultant of: Novartis, Inger M. Hansen: 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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