OP0021 3-YEAR RESULTS OF TAPERING TNFi TO WITHDRAWAL COMPARED TO STABLE TNFi AMONG RHEUMATOID ARTHRITIS PATIENTS IN SUSTAINED REMISSION: A MULTICENTER RANDOMIZED TRIAL
Authors: K. E. Kjørholt, N. P. Sundlisæter, A. B. Aga, J. Sexton, I. C. Olsen, Å. Lexberg, T. M. Madland, H. Fremstad, C. A. Høili, G. Bakland, C. Spada, H. Haukeland, I. M. Hansen, E. Moholt, K. Holten, T. Uhlig, T. K. Kvien, D. H. Solomon, D. Van der Heijde, E. A. Haavardsholm, S. Lillegraven
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> 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. <h3>Objectives:</h3> To assess the 3-year effects of tapering and withdrawal of TNFi versus continuing stable TNFi on disease activity flare, radiographic joint damage and remission status among RA patients in sustained remission. <h3>Methods:</h3> ARCTIC REWIND was a randomized, multicenter, open-label, non-inferiority trial including RA patients in sustained remission for ≥12 months on stable TNFi therapy, with no swollen joints at inclusion. Patients were randomized 1:1 to tapering 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 flare in disease activity over 3 years. A flare was defined as a combination of DAS&gt;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), 3-year change in radiographic joint damage assessed by van der Heijde modified Sharp Score, medication use and adverse events (AE). Data were analysed in the per protocol population adjusting for center as a stratification factor. Flare-free survival was evaluated by Kaplan-Meier and risk of flare by Cox regression, remission status and radiographic change by logistic and linear regression. <h3>Results:</h3> Of 99 randomised patients, 92 received the allocated therapy, and 80 (87%) completed 3-year follow-up. Mean baseline DAS (SD) was 0.8 (0.3) in the tapering TNFi group, and 0.9 (0.4) 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 (<b>Figure 1</b>), with corresponding hazard ratio for flare of 9.4 (3.9 to 22.8), p&lt;0.0001. Most patients regained DAS remission within the next visit after a flare (84% in the tapering group, 67% in the 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 (<b>Figure 2</b>), adjusted risk difference 0-36 months -24% (-33 to -15), p&lt;0.0001 (Boolean 1.0 revealed similar results). The median radiographic changes after 3 years were minimal; 0.5 (95% CI: 0.0 to 2.0) in the tapering group versus 0.5 (0.0 to 1.5) in the stable group, with no significant difference between groups, p-value=0.6. 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, while 10% switched to other types of TNFi or JAK inhibitor treatment in the tapering group, and 11% in the stable group. AE/serious AE occurred in 81%/21% of the patients in the tapering group, and 87%/11% of the patients in the stable group. <h3>Conclusion:</h3> A large majority of RA patients in remission tapering TNFi to withdrawal experienced a flare within three 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. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Kaja E. Kjørholt: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga AbbVie, Lilly, Novartis, Pfizer, Joe Sexton: None declared, Inge C. Olsen Dilafor AB, EU Commission, Åse Lexberg: None declared, Tor Magne Madland Boehringer 2022, Hallvard Fremstad: None declared, Christian A. Høili: None declared, Gunnstein Bakland UCB (Organizing meeting), Cristina Spada Advisory board UCB, Hilde Haukeland Advisory borad for UCB Pharma x2 in 2022., Inger M. Hansen: None declared, Ellen Moholt: None declared, Karen Holten: None declared, Till Uhlig Lilys, Galapagos, Pfizer and UCB, Lilly, Galapagos, Pfizer and UCB, Tore K. Kvien Grünenthal, Janssen, Sandoz, AbbVie, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sandoz, UCB, AbbVie, BMS, Novartis, Pfizer, UCB, Daniel H. Solomon Royalties on several UpToDate chapters on NSAIDs and coxibs. CARRA; unpaid board member., CorEvitas, Horizon, Janssen, Moderna and Novartis provide research support through contracts with Brigham and Women's Hospital for unrelated work., Désirée van der Heijde Director of Imaging Rheumatology, AbbVie, BMS, Galapagos, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, Takeda UCB Pharma., Espen A. Haavardsholm Pfizer, UCB, AbbVie, Participation on a Data Safety Monitoring Board or Advisory Board for Pfizer, AbbVie, Boehringer, Ingelheim, Eli Lilly, Galapagos, Gilead, Novartis, Siri Lillegraven: None declared.