Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)

DIAMOND2 Study Group

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1 Citation (Scopus)

Abstract

Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596). Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, “continue” (Con) or “discontinue” (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety. Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group. Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes.

Original languageEnglish
JournalJournal of gastroenterology
DOIs
Publication statusPublished - 2019 Jan 1

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Crohn Disease
Randomized Controlled Trials
Maintenance
Adrenal Cortex Hormones
Adalimumab
Therapeutics
Odds Ratio
Safety
Serum

Keywords

  • Adalimumab
  • Crohn’s disease
  • Thiopurines

ASJC Scopus subject areas

  • Gastroenterology

Cite this

@article{70d0d8a44ab1428e9d850cea1673ffa0,
title = "Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance: a prospective randomised clinical trial (DIAMOND2)",
abstract = "Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596). Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, “continue” (Con) or “discontinue” (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety. Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group. Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes.",
keywords = "Adalimumab, Crohn’s disease, Thiopurines",
author = "{DIAMOND2 Study Group} and Tadakazu Hisamatsu and Shingo Kato and Reiko Kunisaki and Minoru Matsuura and Masakazu Nagahori and Satoshi Motoya and Motohiro Esaki and Norimasa Fukata and Satoko Inoue and Takeshi Sugaya and Hirotake Sakuraba and Fumihito Hirai and Kenji Watanabe and Takanori Kanai and Makoto Naganuma and Hiroshi Nakase and Yasuo Suzuki and Mamoru Watanabe and Toshifumi Hibi and Masanori Nojima and Takayuki Matsumoto and Katsuya Endo and Hiroyuki Hanai and Taku Kobayashi and Sakiko Hiraoka and Tadakazu Hisamatsu and Yutaka Honda and Takuya Inoue and Shuji Inoue and Tetsuya Ishida and Hiroaki Ito and Ryuichi Iwakiri and Motoyoshi Izumi and Takashi Kagaya and Noriko Kamata and Yumiko Naganawa and Hiroyuki Kaneto and Kazuhito Kani and Fukunori Kinjyo and Hiroki Yasaka and Koichi Kurahara and Lee Kyouwon and Yutaka Yano and Toshiyuki Matsui and Hiroki Tanaka and Yoshinori Munemoto and Yuji Naito and Tomoo Nakagawa and Yoko Yokoyama and Shiro Nakamura",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s00535-019-01582-w",
language = "English",
journal = "Journal of Gastroenterology",
issn = "0944-1174",
publisher = "Springer Japan",

}

TY - JOUR

T1 - Withdrawal of thiopurines in Crohn’s disease treated with scheduled adalimumab maintenance

T2 - a prospective randomised clinical trial (DIAMOND2)

AU - DIAMOND2 Study Group

AU - Hisamatsu, Tadakazu

AU - Kato, Shingo

AU - Kunisaki, Reiko

AU - Matsuura, Minoru

AU - Nagahori, Masakazu

AU - Motoya, Satoshi

AU - Esaki, Motohiro

AU - Fukata, Norimasa

AU - Inoue, Satoko

AU - Sugaya, Takeshi

AU - Sakuraba, Hirotake

AU - Hirai, Fumihito

AU - Watanabe, Kenji

AU - Kanai, Takanori

AU - Naganuma, Makoto

AU - Nakase, Hiroshi

AU - Suzuki, Yasuo

AU - Watanabe, Mamoru

AU - Hibi, Toshifumi

AU - Nojima, Masanori

AU - Matsumoto, Takayuki

AU - Endo, Katsuya

AU - Hanai, Hiroyuki

AU - Kobayashi, Taku

AU - Hiraoka, Sakiko

AU - Hisamatsu, Tadakazu

AU - Honda, Yutaka

AU - Inoue, Takuya

AU - Inoue, Shuji

AU - Ishida, Tetsuya

AU - Ito, Hiroaki

AU - Iwakiri, Ryuichi

AU - Izumi, Motoyoshi

AU - Kagaya, Takashi

AU - Kamata, Noriko

AU - Naganawa, Yumiko

AU - Kaneto, Hiroyuki

AU - Kani, Kazuhito

AU - Kinjyo, Fukunori

AU - Yasaka, Hiroki

AU - Kurahara, Koichi

AU - Kyouwon, Lee

AU - Yano, Yutaka

AU - Matsui, Toshiyuki

AU - Tanaka, Hiroki

AU - Munemoto, Yoshinori

AU - Naito, Yuji

AU - Nakagawa, Tomoo

AU - Yokoyama, Yoko

AU - Nakamura, Shiro

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596). Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, “continue” (Con) or “discontinue” (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety. Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group. Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes.

AB - Background: The risk:benefit ratio of concomitant use of thiopurines with scheduled adalimumab (ADA) maintenance therapy for Crohn’s disease is controversial. The aim of this study is to identify the influence of withdrawal of thiopurines in patients in remission with combination therapy in an open-label, randomised, controlled trial (DIAMOND2; UMIN000009596). Methods: Patients in corticosteroid-free clinical remission (CFCR) for ≥ 6 months with ADA (40 mg, s.c., every other week) scheduled maintenance combined with thiopurines were randomised into two groups, “continue” (Con) or “discontinue” (Dis) group of thiopurines, whereas all other patients kept receiving scheduled ADA maintenance therapy for 52 weeks. The primary endpoint was the proportion of patients in CFCR at week 52. Secondary endpoints were endoscopic remission (ER), trough levels of ADA in serum, and safety. Results: Fifty patients were randomised to Con or Dis groups. Characteristics of patients were not significantly different between the groups. CFCR and ER prevalence at week 52 were not significantly different between groups (log rank, P = 0.704, P = 1.000, respectively). Trough levels of ADA were not significantly different between groups (P = 0.515). The proportion of patients with AAA positivity at week 52 was not significantly different (P = 0.437). ER at week 0 was involved in ER and triple remission at week 52. No serious adverse effects were observed in either group. Conclusion: Continuation of thiopurines > 6 months offers no clear benefit over scheduled ADA monotherapy. CFCR, ER, and ADA trough level at week 52 were not significantly different between groups. ER at week 0 may be involved in better long-term clinical outcomes.

KW - Adalimumab

KW - Crohn’s disease

KW - Thiopurines

UR - http://www.scopus.com/inward/record.url?scp=85065229696&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065229696&partnerID=8YFLogxK

U2 - 10.1007/s00535-019-01582-w

DO - 10.1007/s00535-019-01582-w

M3 - Article

AN - SCOPUS:85065229696

JO - Journal of Gastroenterology

JF - Journal of Gastroenterology

SN - 0944-1174

ER -