L07: 3-year Results of Tapering TNFi to Withdrawal Compared to Stable TNFi Among Rheumatoid Arthritis Patients in Sustained Remission: A Multicenter Randomized Trial

Kaja Kjørholt¹, Nina Sundlisæter¹, Anna-Birgitte Aga¹, Joseph Sexton¹, Inge Christoffer Olsen², Åse Lexberg³, Tor Magne Madland⁴, Hallvard Fremstad⁵, Christian A. Høili⁶, Gunnstein Bakland⁷, Cristina Spada⁸, Hilde Haukeland⁹, Inger Myrnes Hansen¹⁰, Ellen Moholt¹, Karen Holten¹, Till Uhlig¹, Tore Kvien¹, Daniel Solomon¹¹, Désirée van der Heijde¹², Espen Haavardsholm¹ and Siri Lillegraven¹, ¹Center for treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway, ²Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Nepal, ³Department of Rheumatology, Drammen Hospital, Vestre Viken HF, Drammen, Norway, ⁴Department of Rheumatology, Haukeland University Hospital, Bergen, Norway, ⁵Department of Rheumatology, Møre og Romsdal Hospital Trust, Ålesund, Norway, ⁶Department of Rheumatology, Østfold Hospital Trust, Moss, Norway, ⁷Department of Rheumatology, University Hospital of North Norway, Tromsø, Norway, ⁸Department of Rheumatology, Revmatismesykehuset AS, Lillehammer, Norway, ⁹Department of Rheumatology, Martina Hansens Hospital, Bærum, Norway, ¹⁰Deptartment of Rheumatology, Helgelandssykehuset, Mo i Rana, Norway, ¹¹Division of Rheumatology, Brigham and Women's Hospital, Newton, MA, ¹²Department of Rheumatology, Leiden University Medical Center, Meerssen, Netherlands

Background/Purpose: Tapering of tumor necrosis factor inhibitor (TNFi) treatment in patients who have reached sustained remission is debated in current guidelines, and further data are needed regarding the long-term consequences of such strategies. Our aim was to assess the 3-year effect of tapering to withdrawal of TNFi versus continued stable TNFi on disease activity flare and remission status.

Methods: ARCTIC REWIND was a randomized, multicenter, open-label, non-inferiority trial including RA patients in sustained remission for ³12 months on stable TNFi therapy, with no swollen joints at inclusion. Patients were randomized 1:1 to taper to withdrawal of TNFi (four months half-dose, thereafter withdrawal) or continue stable TNFi therapy, with scheduled visits every four months for 3 years. Full-dose TNFi therapy was reinstated if a flare occurred. The primary endpoint of the current study was disease activity flare over 3 years. A flare was defined as a combination of DAS >1.6 (loss of remission status), an increase in DAS ≥0.6 units (change above minimal detectable change) and ≥2 swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Secondary endpoints included remission status (ACR/EULAR Boolean 2.0 and DAS), medication use and adverse events (AE). Flare-free survival was analyzed by Kaplan-Meier, flare by center adjusted Cox regression, and remission status by logistic regression adjusted for baseline status, analyzed in a per protocol population.

Results: Of 99 randomized patients, 92 received the allocated therapy, and 80 (87%) completed 3-year follow-up. Mean baseline DAS was 0.8 in the tapering TNFi group, and 0.9 in the stable TNFi group. csDMARD co-medication was used by 89% in the tapering group and 91% in the stable group. After 3 years, 25% (95% CI: 13 to 38) remained flare-free in the tapering TNFi group compared to 85% (70 to 93) in the stable TNFi group (Fig 1), with corresponding hazard ratio for flare of 9.4 (3.9 to 22.8). Most patients regained DAS remission within the next visit after a flare (81% in tapering group, 67% in stable group). We observed significantly lower Boolean 2.0 remission rates in the tapering TNFi group than the stable TNFi group throughout the study period (Fig 2), adjusted risk difference 0-36 months -25% (-33 to -16), p< 0.001 (Boolean 1.0 revealed similar results). Systemic glucocorticoids (≥1 treatment period during the study) were used by 23% in the tapering TNFi group and 13% in the stable TNFi group during the study, and 10% switched to other types of TNFi or JAK inhibitor treatment in the tapering group, and 11% in the stable group (Table). AE/serious AE occurred in 81%/21% of the patients in the tapering group, and 89%/11% of the patients in the stable group.

Conclusion: A large majority of RA patients in remission tapering TNFi to withdrawal experienced a flare within 3 years, while a minority of patients receiving stable TNFi treatment flared over the same time period. Even though most patients regained remission within the next visit after a flare, TNFi tapering was associated with significantly lower Boolean 2.0 remission rates throughout the study. These findings do not support tapering of TNFi treatment among RA patients in sustained remission.








3-year Results of Tapering TNFi to Withdrawal Compared to Stable TNFi Among Rheumatoid Arthritis Patients in Sustained Remission: A Multicenter Randomized Trial

K. Kjørholt: None; N. Sundlisæter: None; A. Aga: AbbVie, 6, Lilly, 6, Novartis, 6, Pfizer, 6; J. Sexton: None; I. Olsen: Dilafor AB, 2, European Clinical Research Infrastructure Network, 12, Attending meetings and/or travel, European Medicines Agency, 12, Support for attending meetings/and or travel; Å. Lexberg: None; T. Madland: None; H. Fremstad: None; C. Høili: None; G. Bakland: None; C. Spada: UCB, 1; H. Haukeland: UCB, 12, Advisory Board; I. Hansen: None; E. Moholt: None; K. Holten: None; T. Uhlig: Galapagos, Lilly, Pfizer, UCB, 1, 2; T. Kvien: AbbVie, 1, 2, BMS, 5, Galapagos, 2, 5, Grünenthal, 6, janssen, 2, Novartis, 5, Pfizer, 5, Sandoz, 6, UCB, 2; D. Solomon: CorEvitas, 5, Janssen, 5, moderna, 5, Novartis, 5; D. van der Heijde: AbbVie, 2, Argenx, 2, Bayer, 2, Bristol-Myers Squibb(BMS), 2, Galapagos, 2, Glaxo-Smith-Kline, 2, Imaging Rheumatology bv, 12, Director, Janssen, 2, Lilly, 2, Novartis, 2, Pfizer, 2, Takeda, 2, UCB Pharma, 2; E. Haavardsholm: AbbVie, 1, Eli Lilly, 1, UCB, 1; S. Lillegraven: None.