TY - JOUR
T1 - Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study
AU - Nishimoto, Norihiro
AU - Amano, Koichi
AU - Hirabayashi, Yasuhiko
AU - Horiuchi, Takahiko
AU - Ishii, Tomonori
AU - Iwahashi, Mitsuhiro
AU - Iwamoto, Masahiro
AU - Kohsaka, Hitoshi
AU - Kondo, Masakazu
AU - Matsubara, Tsukasa
AU - Mimura, Toshihide
AU - Miyahara, Hisaaki
AU - Ohta, Shuji
AU - Saeki, Yukihiko
AU - Saito, Kazuyoshi
AU - Sano, Hajime
AU - Takasugi, Kiyoshi
AU - Takeuchi, Tsutomu
AU - Tohma, Shigeto
AU - Tsuru, Tomomi
AU - Ueki, Yukitaka
AU - Yamana, Jiro
AU - Hashimoto, Jun
AU - Matsutani, Takaji
AU - Murakami, Miho
AU - Takagi, Nobuhiro
N1 - Funding Information:
Conflict of interest N. Nishimoto has served as a consultant to and received honoraria from Chugai Pharmaceutical Co., Ltd. N.N. also works as a scientific advisor to F. Hoffmann–La Roche, which is developing TCZ in collaboration with Chugai Pharmaceutical Co., Ltd. N.N. also has received research grants from Chugai Pharmaceutical Co. Ltd., Bristol–Myers Japan, and Pfizer Japan Inc. K. Amano has received research grants from Chugai Pharmaceutical Co. Ltd., Astellas Pharm Inc., and Mitsubishi Tanabe Pharma. Y. Hirabayashi has received speakers’ bureau honoraria from Chugai Pharmaceutical Co. Ltd. M. Iwamoto has received a Royalty from Chugai Pharmaceutical Co. Ltd. H. Kohsaka has received research grants, consultant fees, and/or speakers’ bureau honoraria from, Bristol-Myers Japan, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd. T. Mimura received research grants from Abbott Japan, Chugai Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma, and Takeda Pharmaceutical Co. Ltd. T. Takeuchi has received research grants, consultant fees, and/or speakers’ bureau honoraria from Abbott Japan, Bristol-Myers Squibb, Chugai Pharmaceutical Co. Ltd., Eisai Co. Ltd., Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma, Novartis, Pfizer Japan Inc., and Takeda Pharmaceutical Co. Ltd. S. Tohma has received a research grant from Pfizer Japan Inc. and has received subsidies or donations from Health and Labour Sciences Research Grants for Research on Allergic Disease and Immunology, and Chugai Pharmaceutical Co. Ltd. N. Takagi is a full-time employee of Chugai Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.
PY - 2014/1
Y1 - 2014/1
N2 - Objectives 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. Methods Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves. Results 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. Conclusions 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.
AB - Objectives 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. Methods Disease activity was monitored for 56 weeks. The rate of continued efficacy was estimated by Kaplan-Meier curves. Results 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. Conclusions 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.
KW - Drug free
KW - Duration of efficacy
KW - Interleukin 6
KW - Matrix metalloproteinase 3
KW - Rheumatoid arthritis
KW - Tocilizumab
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U2 - 10.3109/14397595.2013.854079
DO - 10.3109/14397595.2013.854079
M3 - Article
C2 - 24261754
AN - SCOPUS:84897569032
SN - 1439-7595
VL - 24
SP - 17
EP - 25
JO - Japanese Journal of Rheumatology
JF - Japanese Journal of Rheumatology
IS - 1
ER -