Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial
OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of...
Published in: | Annals of the Rheumatic Diseases |
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Online Access: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579188/ http://www.ncbi.nlm.nih.gov/pubmed/37607809 https://doi.org/10.1136/ard-2023-224476 |
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ftpubmed:oai:pubmedcentral.nih.gov:10579188 2023-11-12T04:13:44+01:00 Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial Lillegraven, Siri Paulshus Sundlisæter, Nina Aga, Anna-Birgitte Sexton, Joseph Olsen, Inge Christoffer Lexberg, Åse Stavland Madland, Tor Magne Fremstad, Hallvard Høili, Christian A. Bakland, Gunnstein Spada, Cristina Haukeland, Hilde Hansen, Inger Myrnes Moholt, Ellen Uhlig, Till Solomon, Daniel H van der Heijde, Désirée Kvien, Tore K Haavardsholm, Espen A 2023-11 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579188/ http://www.ncbi.nlm.nih.gov/pubmed/37607809 https://doi.org/10.1136/ard-2023-224476 en eng BMJ Publishing Group http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579188/ http://www.ncbi.nlm.nih.gov/pubmed/37607809 http://dx.doi.org/10.1136/ard-2023-224476 © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . Ann Rheum Dis Rheumatoid Arthritis Text 2023 ftpubmed https://doi.org/10.1136/ard-2023-224476 2023-10-22T00:50:51Z OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. METHODS: This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. RESULTS: Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. CONCLUSION: In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. TRIAL REGISTRATION NUMBERS: EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308. Text Arctic PubMed Central (PMC) Arctic Annals of the Rheumatic Diseases 82 11 1394 1403 |
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Rheumatoid Arthritis |
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Rheumatoid Arthritis Lillegraven, Siri Paulshus Sundlisæter, Nina Aga, Anna-Birgitte Sexton, Joseph Olsen, Inge Christoffer Lexberg, Åse Stavland Madland, Tor Magne Fremstad, Hallvard Høili, Christian A. Bakland, Gunnstein Spada, Cristina Haukeland, Hilde Hansen, Inger Myrnes Moholt, Ellen Uhlig, Till Solomon, Daniel H van der Heijde, Désirée Kvien, Tore K Haavardsholm, Espen A Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
topic_facet |
Rheumatoid Arthritis |
description |
OBJECTIVES: Many patients with rheumatoid arthritis (RA) require treatment with tumour necrosis factor inhibitor (TNFi) to reach remission. It is debated whether tapering of TNFi to discontinuation should be considered in sustained remission. The aim of ARCTIC REWIND TNFi was to assess the effect of tapering TNFi to withdrawal compared with stable treatment on the risk of disease activity flares in patients with RA in remission ≥1 year. METHODS: This randomised, open-label, non-inferiority trial was undertaken at nine Norwegian rheumatology departments. Patients with RA in remission ≥12 months on stable TNFi therapy were allocated by computer-based block-randomisation to tapering to discontinuation of TNFi or stable TNFi. Conventional synthetic disease-modifying antirheumatic co-medication was unchanged. The primary endpoint was disease flare during the 12-month study period (non-inferiority margin 20%), assessed in the per-protocol population. RESULTS: Between June 2013 and January 2019, 99 patients were enrolled and 92 received the allocated treatment strategy. Eighty-four patients were included in the per-protocol population. In the tapering TNFi group, 27/43 (63%) experienced a flare during 12 months, compared with 2/41 (5%) in the stable TNFi group; risk difference (95% CI) 58% (42% to 74%). The tapering strategy was not non-inferior to continued stable treatment. The number of total/serious adverse events was 49/3 in the tapering group, 57/2 in the stable group. CONCLUSION: In patients with RA in remission for more than 1 year while using TNFi, an increase in flare rate was reported in those who tapered TNFi to discontinuation. However, most regained remission after reinstatement of full-dose treatment. TRIAL REGISTRATION NUMBERS: EudraCT: 2012-005275-14 and clinicaltrials.gov: NCT01881308. |
format |
Text |
author |
Lillegraven, Siri Paulshus Sundlisæter, Nina Aga, Anna-Birgitte Sexton, Joseph Olsen, Inge Christoffer Lexberg, Åse Stavland Madland, Tor Magne Fremstad, Hallvard Høili, Christian A. Bakland, Gunnstein Spada, Cristina Haukeland, Hilde Hansen, Inger Myrnes Moholt, Ellen Uhlig, Till Solomon, Daniel H van der Heijde, Désirée Kvien, Tore K Haavardsholm, Espen A |
author_facet |
Lillegraven, Siri Paulshus Sundlisæter, Nina Aga, Anna-Birgitte Sexton, Joseph Olsen, Inge Christoffer Lexberg, Åse Stavland Madland, Tor Magne Fremstad, Hallvard Høili, Christian A. Bakland, Gunnstein Spada, Cristina Haukeland, Hilde Hansen, Inger Myrnes Moholt, Ellen Uhlig, Till Solomon, Daniel H van der Heijde, Désirée Kvien, Tore K Haavardsholm, Espen A |
author_sort |
Lillegraven, Siri |
title |
Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
title_short |
Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
title_full |
Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
title_fullStr |
Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
title_full_unstemmed |
Effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
title_sort |
effect of tapered versus stable treatment with tumour necrosis factor inhibitors on disease flares in patients with rheumatoid arthritis in remission: a randomised, open label, non-inferiority trial |
publisher |
BMJ Publishing Group |
publishDate |
2023 |
url |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579188/ http://www.ncbi.nlm.nih.gov/pubmed/37607809 https://doi.org/10.1136/ard-2023-224476 |
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Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
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Arctic |
op_source |
Ann Rheum Dis |
op_relation |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10579188/ http://www.ncbi.nlm.nih.gov/pubmed/37607809 http://dx.doi.org/10.1136/ard-2023-224476 |
op_rights |
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
op_doi |
https://doi.org/10.1136/ard-2023-224476 |
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Annals of the Rheumatic Diseases |
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82 |
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11 |
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