Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: The RRRR study, a randomised controlled trial

Yoshiya Tanaka, Koji Oba, Takao Koike, Nobuyuki Miyasaka, Tsuneyo Mimori, Tsutomu Takeuchi, Shintaro Hirata, Eiichi Tanaka, Hidekata Yasuoka, Yuko Kaneko, Kosaku Murakami, Tomohiro Koga, Kazuhisa Nakano, Koichi Amano, Kazuyasu Ushio, Tatsuya Atsumi, Masayuki Inoo, Kazuhiro Hatta, Shinichi Mizuki, Shouhei NagaokaShinichiro Tsunoda, Hiroaki Dobashi, Nao Horie, Norihiro Sato

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods: In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results: A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

Original languageEnglish
JournalAnnals of the rheumatic diseases
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Rheumatoid Arthritis
Randomized Controlled Trials
Infliximab
Tumor Necrosis Factor-alpha
Therapeutics
Remission Induction
Serum
Methotrexate
Multicenter Studies

Keywords

  • infliximab
  • randomized controlled trials
  • remission
  • rheumatoid arthritis
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis : The RRRR study, a randomised controlled trial. / Tanaka, Yoshiya; Oba, Koji; Koike, Takao; Miyasaka, Nobuyuki; Mimori, Tsuneyo; Takeuchi, Tsutomu; Hirata, Shintaro; Tanaka, Eiichi; Yasuoka, Hidekata; Kaneko, Yuko; Murakami, Kosaku; Koga, Tomohiro; Nakano, Kazuhisa; Amano, Koichi; Ushio, Kazuyasu; Atsumi, Tatsuya; Inoo, Masayuki; Hatta, Kazuhiro; Mizuki, Shinichi; Nagaoka, Shouhei; Tsunoda, Shinichiro; Dobashi, Hiroaki; Horie, Nao; Sato, Norihiro.

In: Annals of the rheumatic diseases, 01.01.2019.

Research output: Contribution to journalArticle

Tanaka, Y, Oba, K, Koike, T, Miyasaka, N, Mimori, T, Takeuchi, T, Hirata, S, Tanaka, E, Yasuoka, H, Kaneko, Y, Murakami, K, Koga, T, Nakano, K, Amano, K, Ushio, K, Atsumi, T, Inoo, M, Hatta, K, Mizuki, S, Nagaoka, S, Tsunoda, S, Dobashi, H, Horie, N & Sato, N 2019, 'Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: The RRRR study, a randomised controlled trial', Annals of the rheumatic diseases. https://doi.org/10.1136/annrheumdis-2019-216169
Tanaka, Yoshiya ; Oba, Koji ; Koike, Takao ; Miyasaka, Nobuyuki ; Mimori, Tsuneyo ; Takeuchi, Tsutomu ; Hirata, Shintaro ; Tanaka, Eiichi ; Yasuoka, Hidekata ; Kaneko, Yuko ; Murakami, Kosaku ; Koga, Tomohiro ; Nakano, Kazuhisa ; Amano, Koichi ; Ushio, Kazuyasu ; Atsumi, Tatsuya ; Inoo, Masayuki ; Hatta, Kazuhiro ; Mizuki, Shinichi ; Nagaoka, Shouhei ; Tsunoda, Shinichiro ; Dobashi, Hiroaki ; Horie, Nao ; Sato, Norihiro. / Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis : The RRRR study, a randomised controlled trial. In: Annals of the rheumatic diseases. 2019.
@article{35367dd396df4ec5ab54b2bf200fa6a2,
title = "Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis: The RRRR study, a randomised controlled trial",
abstract = "Objectives: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods: In this multicentre randomised trial, patients with IFX-na{\"i}ve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results: A total of 337 patients were randomised. At week 54, 39.4{\%} (67/170) in the programmed group and 32.3{\%} (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5{\%} (40/170) and the standard group 21.6{\%} (36/167), respectively (2.2{\%} difference, 95{\%} CI -6.6{\%} to 11.0{\%}; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.",
keywords = "infliximab, randomized controlled trials, remission, rheumatoid arthritis, TNF-α",
author = "Yoshiya Tanaka and Koji Oba and Takao Koike and Nobuyuki Miyasaka and Tsuneyo Mimori and Tsutomu Takeuchi and Shintaro Hirata and Eiichi Tanaka and Hidekata Yasuoka and Yuko Kaneko and Kosaku Murakami and Tomohiro Koga and Kazuhisa Nakano and Koichi Amano and Kazuyasu Ushio and Tatsuya Atsumi and Masayuki Inoo and Kazuhiro Hatta and Shinichi Mizuki and Shouhei Nagaoka and Shinichiro Tsunoda and Hiroaki Dobashi and Nao Horie and Norihiro Sato",
year = "2019",
month = "1",
day = "1",
doi = "10.1136/annrheumdis-2019-216169",
language = "English",
journal = "Annals of the Rheumatic Diseases",
issn = "0003-4967",
publisher = "BMJ Publishing Group",

}

TY - JOUR

T1 - Sustained discontinuation of infliximab with a raising-dose strategy after obtaining remission in patients with rheumatoid arthritis

T2 - The RRRR study, a randomised controlled trial

AU - Tanaka, Yoshiya

AU - Oba, Koji

AU - Koike, Takao

AU - Miyasaka, Nobuyuki

AU - Mimori, Tsuneyo

AU - Takeuchi, Tsutomu

AU - Hirata, Shintaro

AU - Tanaka, Eiichi

AU - Yasuoka, Hidekata

AU - Kaneko, Yuko

AU - Murakami, Kosaku

AU - Koga, Tomohiro

AU - Nakano, Kazuhisa

AU - Amano, Koichi

AU - Ushio, Kazuyasu

AU - Atsumi, Tatsuya

AU - Inoo, Masayuki

AU - Hatta, Kazuhiro

AU - Mizuki, Shinichi

AU - Nagaoka, Shouhei

AU - Tsunoda, Shinichiro

AU - Dobashi, Hiroaki

AU - Horie, Nao

AU - Sato, Norihiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objectives: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods: In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results: A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

AB - Objectives: The aim of this study is to determine whether the 'programmed' infliximab (IFX) treatment strategy (for which the dose of IFX was adjusted based on the baseline serum tumour necrosis factor α (TNF-α)) is beneficial to induction of clinical remission after 54 weeks and sustained discontinuation of IFX for 1 year. Methods: In this multicentre randomised trial, patients with IFX-naïve rheumatoid arthritis with inadequate response to methotrexate were randomised to two groups; patients in programmed treatment group received 3 mg/kg IFX until week 6 and after 14 weeks the dose of IFX was adjusted based on the baseline levels of serum TNF-α until week 54; patients in the standard treatment group received 3 mg/kg of IFX. Patients who achieved a simplified disease activity index (SDAI) ≤3.3 at week 54 discontinued IFX. The primary endpoint was the proportion of patients who sustained discontinuation of IFX at week 106. Results: A total of 337 patients were randomised. At week 54, 39.4% (67/170) in the programmed group and 32.3% (54/167) in the standard group attained remission (SDAI ≤3.3). At week 106, the 1-year sustained discontinuation rate was not significantly different between two groups; the programmed group 23.5% (40/170) and the standard group 21.6% (36/167), respectively (2.2% difference, 95% CI -6.6% to 11.0%; p=0.631). Baseline SDAI <26.0 was a statistically significant predictor of the successfully sustained discontinuation of IFX at week 106. Conclusion: Programmed treatment strategy did not statistically increase the sustained remission rate after 1 year discontinuation of IFX treatment.

KW - infliximab

KW - randomized controlled trials

KW - remission

KW - rheumatoid arthritis

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=85073791370&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073791370&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2019-216169

DO - 10.1136/annrheumdis-2019-216169

M3 - Article

C2 - 31630117

AN - SCOPUS:85073791370

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

SN - 0003-4967

ER -