Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study

Oxford University Press (OUP) - Trang 1-9 - 2013
Norihiro Nishimoto1,2,3, Koichi Amano4, Yasuhiko Hirabayashi5, Takahiko Horiuchi6, Tomonori Ishii7, Mitsuhiro Iwahashi8, Masahiro Iwamoto9, Hitoshi Kohsaka10, Masakazu Kondo11, Tsukasa Matsubara12, Toshihide Mimura13, Hisaaki Miyahara14, Shuji Ohta15, Yukihiko Saeki16, Kazuyoshi Saito17, Hajime Sano18, Kiyoshi Takasugi19, Tsutomu Takeuchi20, Shigeto Tohma21, Tomomi Tsuru22, Yukitaka Ueki23, Jiro Yamana8, Jun Hashimoto16, Takaji Matsutani3, Miho Murakami2,3, Nobuhiro Takagi24
1Osaka Rheumatology Clinic, Osaka, Japan
2Department of Molecular Regulation for Intractable Disease, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan
3Laboratory of Immune Regulation, Wakayama Medical University, Wakayama, Japan
4Department of Rheumatology/Clinical Immunology, Saitama Medical Centre, Saitama Medical University, Saitama, Japan
5Department of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan
6Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
7Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Miyagi, Japan
8Higashihiroshima Memorial Hospital, Higashihiroshima, Japan
9Division of Rheumatology and Clinical Immunology, Jichi Medical University, Tochigi, Japan
10Department of Medicine and Rheumatology, Tokyo Medical and Dental University, Tokyo, Japan
11Kondo Clinic of Rheumatology and Orthopaedic Surgery, Fukuoka, Japan
12Matsubara Mayflower Hospital, Hyogo, Japan
13Department of Rheumatology and Applied Immunology, Saitama Medical University, Saitama, Japan
14National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
15Department of Rheumatology, Taga General Hospital, Ibaraki, Japan
16National Hospital Organization Osaka-Minami Medical Center, Osaka, Japan
17The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, Kitakyushu, Japan
18Division of Rheumatology, Department of Internal Medicine, Hyogo College of Medicine, Hyogo, Japan
19Dohgo Spa Hospital, Ehime, Japan
20Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, Keio University, Tokyo, Japan
21Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan
22PS Clinic, Fukuoka, Japan
23Sasebo Chuo Hospital, Nagasaki, Japan
24Chugai Pharmaceutical Co., Ltd, Tokyo, Japan

Tóm tắt

To investigate the duration of remission and low disease activity (LDA) after cessation of tocilizumab (TCZ) treatment in rheumatoid arthritis patients who showed remission or LDA as assessed by DAS28 in response to preceding TCZ monotherapy, and to explore the factors contributing to prolonged efficacy duration. Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan–Meier curves. A total of 187 patients were eligible. At baseline of this study, median disease duration was 7.8 years, preceding TCZ treatment period was 4.0 years and DAS28 was 1.5. The rate of continued LDA at 52 weeks was 13.4 % according to the Kaplan–Meier estimate. 19 patients (10 %) were completely drug-free and 17 patients (9.1 %) fulfilled DAS28 remission at 52 weeks. Multivariate Cox regression analysis identified low serum IL-6 and normalisation of MMP-3 levels at cessation of TCZ as independent predictive markers for longer duration of LDA. In patients with low serum IL-6 (<12.9 pg/mL) and normal MMP-3 levels, the rate of continued LDA reached 38.0 % at 52 weeks. TCZ monotherapy may induce biologics-free remission or LDA without concomitant use of synthetic DMARDs. Serum levels of IL-6 and MMP-3 are useful markers for identifying patients who could discontinue TCZ without acute disease flare.

Tài liệu tham khảo

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