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Research ArticleArticle

Can Patients With Controlled Rheumatoid Arthritis Taper Methotrexate From Targeted Therapy and Sustain Remission? A Systematic Review and Metaanalysis

Charis F. Meng, Diviya A. Rajesh, Deanna P. Jannat-Khah, Bridget Jivanelli and Vivian P. Bykerk
The Journal of Rheumatology August 2022, jrheum.220152; DOI: https://doi.org/10.3899/jrheum.220152
Charis F. Meng
This research was supported by the Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York, USA. C.F. Meng MD, V.P. Bykerk, MD, Division of Rheumatology, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. D.A. Rajesh, BA, Division of Rheumatology, Hospital for Special Surgery. D.P. Jannat-Khah, DRPH, MSPH, Division of Rheumatology, Epidemiology and Biostatistics CORE, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. B. Jivanelli, MLIS, Kim Barrett Memorial Library, HSS Education Institute, Hospital for Special Surgery, New York, NY, USA. DPJK declares stock ownership in AstraZeneca, Cytodyn, and Walgreens. VPB declares institutional grants from BMS and Amgen; honoraria or consulting fees from Amgen, BMS, Genzyme, Gilead, Janssen, Pfizer, Sanofi-Aventis, and UCB; support by the National Institutes of Health (NIH; National Institute of Allergy and Infectious Diseases/National Institute of Arthritis and Musculoskeletal and Skin; grants 1UH2AR067691-01 and 11652401) and The Cedar Hill Foundation; and participation on the Data Safety Monitoring Board of NIH Cell Therapies. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. C.F. Meng, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA. Email: mengc@hss.edu. Accepted for publication July 27, 2022.
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Diviya A. Rajesh
This research was supported by the Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York, USA. C.F. Meng MD, V.P. Bykerk, MD, Division of Rheumatology, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. D.A. Rajesh, BA, Division of Rheumatology, Hospital for Special Surgery. D.P. Jannat-Khah, DRPH, MSPH, Division of Rheumatology, Epidemiology and Biostatistics CORE, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. B. Jivanelli, MLIS, Kim Barrett Memorial Library, HSS Education Institute, Hospital for Special Surgery, New York, NY, USA. DPJK declares stock ownership in AstraZeneca, Cytodyn, and Walgreens. VPB declares institutional grants from BMS and Amgen; honoraria or consulting fees from Amgen, BMS, Genzyme, Gilead, Janssen, Pfizer, Sanofi-Aventis, and UCB; support by the National Institutes of Health (NIH; National Institute of Allergy and Infectious Diseases/National Institute of Arthritis and Musculoskeletal and Skin; grants 1UH2AR067691-01 and 11652401) and The Cedar Hill Foundation; and participation on the Data Safety Monitoring Board of NIH Cell Therapies. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. C.F. Meng, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA. Email: mengc@hss.edu. Accepted for publication July 27, 2022.
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Deanna P. Jannat-Khah
This research was supported by the Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York, USA. C.F. Meng MD, V.P. Bykerk, MD, Division of Rheumatology, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. D.A. Rajesh, BA, Division of Rheumatology, Hospital for Special Surgery. D.P. Jannat-Khah, DRPH, MSPH, Division of Rheumatology, Epidemiology and Biostatistics CORE, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. B. Jivanelli, MLIS, Kim Barrett Memorial Library, HSS Education Institute, Hospital for Special Surgery, New York, NY, USA. DPJK declares stock ownership in AstraZeneca, Cytodyn, and Walgreens. VPB declares institutional grants from BMS and Amgen; honoraria or consulting fees from Amgen, BMS, Genzyme, Gilead, Janssen, Pfizer, Sanofi-Aventis, and UCB; support by the National Institutes of Health (NIH; National Institute of Allergy and Infectious Diseases/National Institute of Arthritis and Musculoskeletal and Skin; grants 1UH2AR067691-01 and 11652401) and The Cedar Hill Foundation; and participation on the Data Safety Monitoring Board of NIH Cell Therapies. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. C.F. Meng, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA. Email: mengc@hss.edu. Accepted for publication July 27, 2022.
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Bridget Jivanelli
This research was supported by the Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York, USA. C.F. Meng MD, V.P. Bykerk, MD, Division of Rheumatology, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. D.A. Rajesh, BA, Division of Rheumatology, Hospital for Special Surgery. D.P. Jannat-Khah, DRPH, MSPH, Division of Rheumatology, Epidemiology and Biostatistics CORE, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. B. Jivanelli, MLIS, Kim Barrett Memorial Library, HSS Education Institute, Hospital for Special Surgery, New York, NY, USA. DPJK declares stock ownership in AstraZeneca, Cytodyn, and Walgreens. VPB declares institutional grants from BMS and Amgen; honoraria or consulting fees from Amgen, BMS, Genzyme, Gilead, Janssen, Pfizer, Sanofi-Aventis, and UCB; support by the National Institutes of Health (NIH; National Institute of Allergy and Infectious Diseases/National Institute of Arthritis and Musculoskeletal and Skin; grants 1UH2AR067691-01 and 11652401) and The Cedar Hill Foundation; and participation on the Data Safety Monitoring Board of NIH Cell Therapies. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. C.F. Meng, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA. Email: mengc@hss.edu. Accepted for publication July 27, 2022.
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Vivian P. Bykerk
This research was supported by the Inflammatory Arthritis Center, Hospital for Special Surgery, New York, New York, USA. C.F. Meng MD, V.P. Bykerk, MD, Division of Rheumatology, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. D.A. Rajesh, BA, Division of Rheumatology, Hospital for Special Surgery. D.P. Jannat-Khah, DRPH, MSPH, Division of Rheumatology, Epidemiology and Biostatistics CORE, Hospital for Special Surgery, and Department of Medicine, Weill Cornell Medical College. B. Jivanelli, MLIS, Kim Barrett Memorial Library, HSS Education Institute, Hospital for Special Surgery, New York, NY, USA. DPJK declares stock ownership in AstraZeneca, Cytodyn, and Walgreens. VPB declares institutional grants from BMS and Amgen; honoraria or consulting fees from Amgen, BMS, Genzyme, Gilead, Janssen, Pfizer, Sanofi-Aventis, and UCB; support by the National Institutes of Health (NIH; National Institute of Allergy and Infectious Diseases/National Institute of Arthritis and Musculoskeletal and Skin; grants 1UH2AR067691-01 and 11652401) and The Cedar Hill Foundation; and participation on the Data Safety Monitoring Board of NIH Cell Therapies. The remaining authors declare no conflicts of interest relevant to this article. Address correspondence to Dr. C.F. Meng, Hospital for Special Surgery, 535 E 70th Street, New York, NY 10021, USA. Email: mengc@hss.edu. Accepted for publication July 27, 2022.
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Abstract

Objective To determine the risk of not being able to sustain remission after tapering methotrexate (MTX) from targeted therapy in patients with controlled rheumatoid arthritis (RA).

Methods A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Library for studies reporting remission outcomes after tapering MTX from targeted therapies in RA. Full-text articles and abstracts reported in English were included. Metaanalyses were conducted using random-effects models. Forest and funnel plots were created.

Results A total of 10 articles were included. Studies evaluated MTX being tapered from combination treatment with tumor necrosis factor inhibitors, tocilizumab, abatacept, and tofacitinib. A total of 9 studies used a randomized design and 1 was observational. Out of 10 studies, 3 focused on early RA (ie, < 1 yr). The MTX-tapering strategy was gradual in 2 studies and rapid in 8 studies. Follow-up ranged from 3 to 18 months in randomized trials and up to 3 years in the observational study. Our metaanalysis, which included 2000 participants with RA from 10 studies, showed that patients who tapered MTX from targeted therapy had a 10% reduction in the ability to sustain remission and an overall pooled risk ratio of 0.90 (95% CI 0.84-0.97). There was no heterogeneity (I2 = 0%, P = 0.94). Our funnel plot indicated minimal publication bias.

Conclusion Patients with controlled RA may taper MTX from targeted therapy with a 10% reduction in the ability to sustain remission for up to 18 months. Longer follow-up studies with attention to radiographic, functional, and patient-reported outcomes are needed. The risk of disease worsening should be discussed with the patient with careful follow-up and prompt retreatment of disease worsening.

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The Journal of Rheumatology
Vol. 50, Issue 1
1 Jan 2023
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Can Patients With Controlled Rheumatoid Arthritis Taper Methotrexate From Targeted Therapy and Sustain Remission? A Systematic Review and Metaanalysis
Charis F. Meng, Diviya A. Rajesh, Deanna P. Jannat-Khah, Bridget Jivanelli, Vivian P. Bykerk
The Journal of Rheumatology Aug 2022, jrheum.220152; DOI: 10.3899/jrheum.220152

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Can Patients With Controlled Rheumatoid Arthritis Taper Methotrexate From Targeted Therapy and Sustain Remission? A Systematic Review and Metaanalysis
Charis F. Meng, Diviya A. Rajesh, Deanna P. Jannat-Khah, Bridget Jivanelli, Vivian P. Bykerk
The Journal of Rheumatology Aug 2022, jrheum.220152; DOI: 10.3899/jrheum.220152
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