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

Norihiro Nishimoto; Koichi Amano; Yasuhiko Hirabayashi; Takahiko Horiuchi; Tomonori Ishii; Mitsuhiro Iwahashi; Masahiro Iwamoto; Hitoshi Kohsaka; Masakazu Kondo; Tsukasa Matsubara; Toshihide Mimura; Hisaaki Miyahara; Shuji Ohta; Yukihiko Saeki; Kazuyoshi Saito; Hajime Sano; Kiyoshi Takasugi; Tsutomu Takeuchi; Shigeto Tohma; Tomomi Tsuru; Yukitaka Ueki; Jiro Yamana; Jun Hashimoto; Takaji Matsutani; Miho Murakami; Nobuhiro Takagi

doi:10.1007/s10165-013-0894-z

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

Norihiro Nishimoto, Koichi Amano, Yasuhiko Hirabayashi, Takahiko Horiuchi, Tomonori Ishii, Mitsuhiro Iwahashi, Masahiro Iwamoto, Hitoshi Kohsaka, Masakazu Kondo, Tsukasa Matsubara, Toshihide Mimura, Hisaaki Miyahara, Shuji Ohta, Yukihiko Saeki, Kazuyoshi Saito, Hajime Sano, Kiyoshi Takasugi, Tsutomu Takeuchi, Shigeto Tohma, Tomomi TsuruYukitaka Ueki, Jiro Yamana, Jun Hashimoto, Takaji Matsutani, Miho Murakami, Nobuhiro Takagi

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1-9
Number of pages	9
Journal	Modern Rheumatology
DOIs	https://doi.org/10.1007/s10165-013-0894-z
Publication status	Accepted/In press - 2013

Keywords

Drug free
Duration of efficacy
Interleukin 6
Matrix metalloproteinase 3
Rheumatoid arthritis
Tocilizumab

ASJC Scopus subject areas

Rheumatology

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Nishimoto, N., Amano, K., Hirabayashi, Y., Horiuchi, T., Ishii, T., Iwahashi, M., Iwamoto, M., Kohsaka, H., Kondo, M., Matsubara, T., Mimura, T., Miyahara, H., Ohta, S., Saeki, Y., Saito, K., Sano, H., Takasugi, K., Takeuchi, T., Tohma, S., ... Takagi, N. (Accepted/In press). Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study. Modern Rheumatology, 1-9. https://doi.org/10.1007/s10165-013-0894-z

Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study. / Nishimoto, Norihiro; Amano, Koichi; Hirabayashi, Yasuhiko; Horiuchi, Takahiko; Ishii, Tomonori; Iwahashi, Mitsuhiro; Iwamoto, Masahiro; Kohsaka, Hitoshi; Kondo, Masakazu; Matsubara, Tsukasa; Mimura, Toshihide; Miyahara, Hisaaki; Ohta, Shuji; Saeki, Yukihiko; Saito, Kazuyoshi; Sano, Hajime; Takasugi, Kiyoshi; Takeuchi, Tsutomu; Tohma, Shigeto; Tsuru, Tomomi; Ueki, Yukitaka; Yamana, Jiro; Hashimoto, Jun; Matsutani, Takaji; Murakami, Miho; Takagi, Nobuhiro.

In: Modern Rheumatology, 2013, p. 1-9.

Research output: Contribution to journal › Article › peer-review

Nishimoto, N, Amano, K, Hirabayashi, Y, Horiuchi, T, Ishii, T, Iwahashi, M, Iwamoto, M, Kohsaka, H, Kondo, M, Matsubara, T, Mimura, T, Miyahara, H, Ohta, S, Saeki, Y, Saito, K, Sano, H, Takasugi, K, Takeuchi, T, Tohma, S, Tsuru, T, Ueki, Y, Yamana, J, Hashimoto, J, Matsutani, T, Murakami, M & Takagi, N 2013, 'Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study', Modern Rheumatology, pp. 1-9. https://doi.org/10.1007/s10165-013-0894-z

Nishimoto, Norihiro ; Amano, Koichi ; Hirabayashi, Yasuhiko ; Horiuchi, Takahiko ; Ishii, Tomonori ; Iwahashi, Mitsuhiro ; Iwamoto, Masahiro ; Kohsaka, Hitoshi ; Kondo, Masakazu ; Matsubara, Tsukasa ; Mimura, Toshihide ; Miyahara, Hisaaki ; Ohta, Shuji ; Saeki, Yukihiko ; Saito, Kazuyoshi ; Sano, Hajime ; Takasugi, Kiyoshi ; Takeuchi, Tsutomu ; Tohma, Shigeto ; Tsuru, Tomomi ; Ueki, Yukitaka ; Yamana, Jiro ; Hashimoto, Jun ; Matsutani, Takaji ; Murakami, Miho ; Takagi, Nobuhiro. / Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study. In: Modern Rheumatology. 2013 ; pp. 1-9.

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abstract = "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.",

keywords = "Drug free, Duration of efficacy, Interleukin 6, Matrix metalloproteinase 3, Rheumatoid arthritis, Tocilizumab",

author = "Norihiro Nishimoto and Koichi Amano and Yasuhiko Hirabayashi and Takahiko Horiuchi and Tomonori Ishii and Mitsuhiro Iwahashi and Masahiro Iwamoto and Hitoshi Kohsaka and Masakazu Kondo and Tsukasa Matsubara and Toshihide Mimura and Hisaaki Miyahara and Shuji Ohta and Yukihiko Saeki and Kazuyoshi Saito and Hajime Sano and Kiyoshi Takasugi and Tsutomu Takeuchi and Shigeto Tohma and Tomomi Tsuru and Yukitaka Ueki and Jiro Yamana and Jun Hashimoto and Takaji Matsutani and Miho Murakami and Nobuhiro Takagi",

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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

PY - 2013

Y1 - 2013

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.

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KW - Drug free

KW - Duration of efficacy

KW - Interleukin 6

KW - Matrix metalloproteinase 3

KW - Rheumatoid arthritis

KW - Tocilizumab

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