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Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: the RRRR study, a randomised controlled trial
  1. Yoshiya Tanaka1,
  2. Koji Oba2,
  3. Takao Koike3,
  4. Nobuyuki Miyasaka4,
  5. Tsuneyo Mimori5,
  6. Tsutomu Takeuchi6,
  7. Shintaro Hirata7,
  8. Eiichi Tanaka8,
  9. Hidekata Yasuoka6,
  10. Yuko Kaneko6,
  11. Kosaku Murakami9,
  12. Tomohiro Koga10,
  13. Kazuhisa Nakano1,
  14. Koichi Amano11,
  15. Kazuyasu Ushio12,
  16. Tatsuya Atsumi3,
  17. Masayuki Inoo13,
  18. Kazuhiro Hatta14,
  19. Shinichi Mizuki15,
  20. Shouhei Nagaoka16,
  21. Shinichiro Tsunoda17,
  22. Hiroaki Dobashi18,
  23. Nao Horie2,
  24. Norihiro Sato2
  1. 1 Department of the First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
  2. 2 Clinical Research and Medical Innovation Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan
  3. 3 Department of Clinical Immunology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
  4. 4 Department of Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan
  5. 5 Department of Rheumatology, Ijinkai Takeda General Hospital, Kyoto, Japan
  6. 6 Department of Rheumatology, Keio University, School of Medicine, Tokyo, Japan
  7. 7 Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima, Japan
  8. 8 Department of Rheumatology, School of Medicine, Tokyo Women's Medical University, Tokyo, Japan
  9. 9 Deapartment of Rheumatology and Clinical Immunology, Kyoto University, Kyoto, Japan
  10. 10 Department of Immunology and Rheumatology, Nagasaki University, Nagasaki, Japan
  11. 11 Department of Rheumatology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan
  12. 12 Ushio Clinic, Osaka, Japan
  13. 13 Utazu Hama Clinic, Ayauta-gun, Kagawa, Japan
  14. 14 Department of General Medicine, Tenri Hospital, Tenri, Japan
  15. 15 The Centre for Rheumatic Diseases, Matsuyama Red Cross Hospital, Matsuyama, Ehime, Japan
  16. 16 Department of Rheumatology, Yokohama Minami Kyosai Hospital, Yokohama, Japan
  17. 17 Division of Rheumatology, Hyogo College of Medicine, Nishinomiya, Japan
  18. 18 Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Miki, Japan
  1. Correspondence to Dr Yoshiya Tanaka, First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; tanaka{at}med.uoeh-u.ac.jp

Abstract

Objectives The aim of this study is to determine whether the ‘programmed’ infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year.

Methods In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106.

Results A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI −6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106.

Conclusion Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

  • rheumatoid arthritis
  • infliximab
  • TNF-α
  • randomized controlled trials
  • remission

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    Disclaimer : This is a summary of a scientific article written by a medical professional (“the Original Article”). The Summary is written to assist non medically trained readers to understand general points of the Original Article. It is supplied “as is” without any warranty. You should note that the Original Article (and Summary) may not be fully relevant nor accurate as medical science is constantly changing and errors can occur. It is therefore very important that readers not rely on the content in the Summary and consult their medical professionals for all aspects of their health care and only rely on the Summary if directed to do so by their medical professional. Please view our full Website Terms and Conditions.
    Copyright © 2020 BMJ Publishing Group Ltd & European League Against Rheumatism. Medical professionals may print copies for their and their patients and students non commercial use. Other individuals may print a single copy for their personal, non commercial use. For other uses please contact our Rights and Licensing Team.

  • Lay summary

    Disclaimer : This is a summary of a scientific article written by a medical professional (“the Original Article”). The Summary is written to assist non medically trained readers to understand general points of the Original Article. It is supplied “as is” without any warranty. You should note that the Original Article (and Summary) may not be fully relevant nor accurate as medical science is constantly changing and errors can occur. It is therefore very important that readers not rely on the content in the Summary and consult their medical professionals for all aspects of their health care and only rely on the Summary if directed to do so by their medical professional. Please view our full Website Terms and Conditions.
    Copyright © 2020 BMJ Publishing Group Ltd & European League Against Rheumatism. Medical professionals may print copies for their and their patients and students non commercial use. Other individuals may print a single copy for their personal, non commercial use. For other uses please contact our Rights and Licensing Team.

Footnotes

  • Handling editor Josef S Smolen

  • Contributors All authors made essential and valuable contributions to the patient assessment, data collection and manuscript. In addition to the above, YT contributed to study design, study conduct, data analysis, KO, NH and NS did data management and data analysis and TaKo, NM, TM and TsTa did the study design and study conduct.

  • Funding This is an investigator-initiated trial sponsored by a Research Grant-In-Aid for Scientific Research from the Ministry of Health, Labor and Welfare of Japan. A radiological evaluation was funded by Mitsubishi Tanabe Pharma Co, Ltd.

  • Competing interests YT has received consulting fees, speaking fees and/or honoraria from AbbVie GK; Chugai Pharmaceutical Co Ltd; Daiichi-Sankyo Co Ltd; Bristol-Myers, Mitsubishi Tanabe Pharma Co; Astellas Pharma Inc; Takeda Pharmaceutical Co Ltd; Pfizer Japan Inc; Teijin Pharma; Asahikasei Pharma Corp; YL Biologics; Sanofi KK: Janssen Pharmaceutical KK; Eli Lilly Japan KK and GlaxoSmithKline KK and has received research grants from Mitsubishi Tanabe Pharma Co; Takeda Pharmaceutical Co, Ltd; Daiichi Sankyo Co Ltd; Chugai Pharmaceutical Co Ltd; Bristol-Myers KK; MSD KK; Astellas Pharma Inc; AbbVie GK; Eisai Co Ltd K Oba has received honoraria from Takeda Pharmaceutical Co Ltd; Ono Pharmaceutical Co Ltd; Eisai Co Ltd; Chugai Pharmaceutical Co Ltd; Daiichi- Sankyo Co Ltd. TT has received grants from Astellas Pharma Inc and Pfizer Japan, Inc; Chugai Pharmaceutical Co Ltd; Daiichi Sankyo Co Ltd; Takeda Pharmaceutical Co Ltd; AbbVie GK; Asahikasei Pharma Corp; Mitsubishi Tanabe Pharma Co; Pfizer Japan Inc; Eisai Co Ltd; AYUMI Pharmaceutical Co; Nipponkayaku Co Ltd; Novartis Pharma KK; Shionogi AbbVie GK; AYUMI Pharmaceutical Co; Eisai Co Ltd; Gilead Sciences, Inc; GlaxoSmithKline KK; Sanofi KK; Taiho Pharmaceutical Co Ltd; Mitsubishi Tanabe Pharma Co; Diaichi Sankyo Co Ltd; Chugai Pharmaceutical Co Ltd; Taisho Pharmaceutical Co Ltd; Eli Lilly Japan KK; Novartis Pharma KK; Boehringer-ingelheim Co Ltd; Nipponkayaku Co Ltd; Pfizer Japan Inc; Bristol–Myers KK; Janssen Pharmaceutical KK; UCB Japan Co Ltd. TM received research grants and/or speaking fees from Asahikasei Pharma Corp; Astellas Pharma Inc; AYUMI Pharmaceutical Corporation; Bristol-Myers Squibb; Chugai Pharmaceutical Co Ltd; Diaichi-Sankyo Co Ltd; Eisai Co Ltd; Eli Lilly Japan KK; Mitsubishi-Tanabe Pharma Co; MSD KK; Nippon Kayaku Co Ltd; Pfizer Japan Inc; Sanofi KK; Takeda Pharmaceutical Co Ltd. TK has received speaking fees from AbbVie GK; ASKA Pharmaceutical Co Ltd; Astellas Pharma Inc; Bristol-Myers KK; Chugai Pharmaceutical Co Ltd; Diaichi-Sankyo Co Ltd; Eisai Co Ltd; Mitsubishi Tanabe Pharma Co; Pfizer Japan Inc; Teijin Pharma; UCB Pharma and consulting fees from Bristol-Myers KK; Eli Lilly Japan KK; Pfizer Japan Inc; Diaichi-Sankyo Co Ltd; Sanofi KK. SH has received research grants from Eli Lilly Japan KK; UCB Pharma; consultancy fee from Bristol-Myers Squibb; Celgene KK; Janssen Pharmaceutical KK; Novartis Pharma KK and speaker’s fees from AbbVie GK; Asahikasei Pharma Corp; Astellas Pharma Inc; AYUMI Pharmaceutical Co; Bristol-Myers Squibb; Chugai Pharmaceutical Co Ltd; Eisai Co Ltd; Eli Lilly Japan KK; Janssen Pharmaceutical KK; Kissei Pharmaceutical Co Ltd; Pfizer Japan Inc; Sanofi KK; Takeda Pharmaceutical Co Ltd; Mitsubishi Tanabe Pharma Co; UCB Pharma. ET has received lecture fees or consulting fees from Asahi Kasei pharma co; Bristol Myers Squibb; Chugai Pharmaceutical Co Ltd; Diaichi Sankyo Co Ltd; Eisai Co Ltd; Janssen Pharmaceutical KK; Nippon Kayaku Co Ltd; Pfizer Japan Inc; Takeda Pharmaceutical Co Ltd; Taisho Toyama Pharmaceutical Co Ltd; UCB Pharma. YK has received grants or speaking fees from AbbVie GK; Astellas Pharma Inc; AYUMI Pharmaceutical Co; Bristol-Myers Squibb; Chugai Pharmaceutical Co Ltd; Eisai Co Ltd; Eli Lilly Japan KK; Hisamitsu Pharmaceutical Co Inc; Janssen Pharmaceutical KK; Novartis Pharma KK; Pfizer Japan Inc; Sanofi KK; Takeda Pharmaceutical Co Ltd; Mitsubishi Tanabe Pharma Co; UCB Pharma. KN has received speaking fees from UCB Pharma; Astellas Pharma Inc; Mitsubishi Tanabe Pharma Co and research grants from Mitsubishi Tanabe Pharma Co; Eisai Co Ltd. KA has received research grants from Asahi Kasei Pharma Co; Chugai Pharmaceutical Co Ltd and honoraria from Astellas Pharma Inc; Eli Lilly Japan KK; Pfizer Japan Inc; Mitsubishi Tanabe Pharma Co Ltd.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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