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

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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.

Original languageEnglish
Pages (from-to)17-25
Number of pages9
JournalModern Rheumatology
Volume24
Issue number1
DOIs
Publication statusPublished - Jan 1 2014

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Pharmaceutical Preparations
Matrix Metalloproteinases
Interleukin-6
Serum
Withholding Treatment
Antirheumatic Agents
tocilizumab
Kaplan-Meier Estimate
Acute Disease
Biological Products
Rheumatoid Arthritis
Regression Analysis
Therapeutics

All Science Journal Classification (ASJC) codes

  • Rheumatology

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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, Vol. 24, No. 1, 01.01.2014, p. 17-25.

Research output: Contribution to journalArticle

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 2014, 'Drug free REmission/low disease activity after cessation of tocilizumab (Actemra) Monotherapy (DREAM) study', Modern Rheumatology, vol. 24, no. 1, pp. 17-25. https://doi.org/10.3109/14397595.2013.854079
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. 2014 ; Vol. 24, No. 1. pp. 17-25.
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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.",
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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

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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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