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Ann Rheum Dis 69:1286-1291 doi:10.1136/ard.2009.121491
  • Clinical and epidemiological research
  • Extended report

Discontinuation of infliximab after attaining low disease activity in patients with rheumatoid arthritis: RRR (remission induction by Remicade in RA) study

Open Access
  1. for the RRR study investigators
  1. 1The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
  2. 2Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, Keio University, Tokyo, Japan
  3. 3Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto, Japan
  4. 4Department of Rheumatology/Clinical Immunology, Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan
  5. 5Department of Medicine and Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan
  6. 6Department of Medicine II, Hokkaido University, Sapporo, Japan
  1. Correspondence to Professor Yoshiya Tanaka, The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan, 1-1 Iseigaoka, Kitakyushu 807-8555 Japan; tanaka{at}med.uoeh-u.ac.jp
  • Accepted 9 January 2010
  • Published Online First 1 April 2010

Abstract

Background Tumour necrosis factor (TNF) inhibitors enable tight control of disease activity in patients with rheumatoid arthritis (RA). Discontinuation of TNF inhibitors after acquisition of low disease activity (LDA) is important for safety and economic reasons.

Objective To determine whether infliximab might be discontinued after achievement of LDA in patients with RA and to evaluate progression of articular destruction during the discontinuation.

Methods 114 patients with RA who had received infliximab treatment, and whose Disease Activity Score, including a 28-joint count (DAS28) was <3.2 (LDA) for 24 weeks, were studied.

Results The mean disease duration of the 114 patients was 5.9 years, mean DAS28 5.5 and mean modified total Sharp score (mTSS) 63.3. After maintaining LDA for >24 weeks by infliximab treatment, the drug was discontinued and DAS28 in 102 patients was evaluated at year 1. Fifty-six patients (55%) continued to have DAS28<3.2 and 43% reached DAS<2.6 at 1 year after discontinuing infliximab. For 46 patients remission induction by Remicade in RA (RRR) failed: disease in 29 patients flared within 1 year and DAS28 was >3.2 at year 1 in 17 patients. Yearly progression of mTSS (ΔTSS) remained <0.5 in 67% and 44% of the RRR-achieved and RRR-failed groups, respectively. The estimated ΔmTSS was 0.3 and 1.6 and Health Assessment Questionnaire-Disability Index was 0.174 and 0.614 in the RRR-achieved and RRR-failed groups, respectively, 1 year after the discontinuation.

Conclusion After attaining LDA by infliximab, 56 (55%) of the 102 patients with RA were able to discontinue infliximab for >1 year without progression of radiological articular destruction.

Footnotes

  • Funding Supported in part by a research grant-in-aid for scientific research by the Ministry of Health, Labour and Welfare of Japan, the Ministry of Education, Culture, Sports, Science and Technology of Japan and the University of Occupational and Environmental Health, Japan.

  • Competing interests YT has received consultant fees from Mitsubishi-Tanabe Pharma, Pfizer Inc; lecture fees from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical Co Ltd, Abbott, Eisai Pharma, Chugai Pharma. TT has received consultant fees from Mitsubishi-Tanabe Pharma, Wyeth Japan, Abbott, Eisai Pharma, Janssen Pharma, Chugai Pharma, Bristol-Myers-Squibb, Novartis; lecture fees from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical Co Ltd, Abbott, Eisai Pharma, Chugai Pharma. HK has received lecture fees from Mitsubishi-Tanabe Pharma, Centocor, Wyeth Japan, Takeda Pharmaceutical Co Ltd, Abbott, Eisai Pharma, Chugai Pharma. NM has received consultant fees from Mitsubishi-Tanabe Pharma; Abbott, Eisai Pharma, Janssen Pharma, Chugai Pharma, Bristol-Myers-Squibb; lecture fees from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical Co Ltd, Wyeth Japan, Abbott, Eisai Pharma, Chugai Pharma. TK has received consultant fees from Bristol-Myers-Squibb, Abbott; lecture fees from Mitsubishi-Tanabe Pharma, Takeda Pharmaceutical Co Ltd, Wyeth Japan, Abbott, Eisai Pharma, Chugai Pharma.

  • Patient consent Obtained.

  • Ethics approval This study is an observational study and is registered with the University Hospital Medical Information Network-Clinical trials Registry, number R000002571. Also, ethics committees of the participating centres approved the study protocol.

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

  • RRR study investigators (other than the authors) Shunsuke Fukuyo (University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan), Hayato Nagasawa (Saitama Medical Centre, Saitama Medical University, Kawagoe, Japan), Yukitaka Ueki (Sasebo Central Hospital, Sasebo, Japan), Hideo Ohstubo (Japanese Red Cross Kagoshima Hospital, Kagoshima, Japan), Kosaku Murakami (Kyoto University, Kyoto, Japan), Hiroaki Dobashi (Kagawa University, Kagawa, Japan), Shigeru Honjo (Saiseikai Takaoka Hospital, Takaoka, Japan), Teruhisa Azuma (Tenri Hospital), Masato Yagita, Saori Hatachi and Kazuyasu Ushio (Kitano Hospital, Tazuke Kofukai Medical Resarch Institute and Ushio clinic, Osaka, Japan), Toshihide Mimura and Yuji Akiyama (Saitama Medical University, Saitama, Japan), Hiromitsu Takemori (Aomori Prefectural Hospital), Takao Takeuchi (Osaka Red Cross Hospital, Hayaishi Hospital, Osaka, Japan),Tsuyoshi Kasama (Showa University, Tokyo, Japan), Shunsuke Mori (Kumamoto Saishunsou National Hospital, Kumamoto, Japan), Shouhei Nagaoka (Yokohama Minami Kyousai Hospital, Yokohama, Japan), Masaaki Inaba and Hitoshi Goto (Osaka City University, Osaka, Japan), Toshihiko Hidaka (Zenjinkai Shimin-no-Mori Hospital, Miyazaki, Japan), Yasuaki Okuda (Dohgo Spa Hospital, Matsuyama, Japan), Yoshinari Takasaki and Naoto Tamura (Juntendo University, Tokyo, Japan), Kazuhide Tanimura (Tokeidai Memorial Hospital, Sapporo, Japan), Takayuki Sumida (University of Tsukuba, Tsukuba, Japan), Katsumi Eguchi (Nagasaki University, Nagasaki, Japan), Yho Ishiguro (Hirosaki University, Horosaki, Japan), Takeo Sakurai (Inoue Hospital, Gunma, Japan).

This paper is freely available online under the BMJ Journals unlocked scheme, see http://ard.bmj.com/info/unlocked.dtl