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J Gastroenterol. 2019 Oct;54(10):860-870. doi: 10.1007/s00535-019-01582-w. Epub 2019 Apr 30.

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

Author information

1
Division of Gastroenterology and Hepatology, Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka-shi, Tokyo, 181-8611, Japan. thisamatsu@ks.kyorin-u.ac.jp.
2
Department of Gastroenterology and Hepatology, Saitama Medical Centre, Saitama Medical University, Saitama, Japan.
3
Inflammatory Bowel Disease Centre, Yokohama City University Medical Center, Kanagawa, Japan.
4
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
5
Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
6
Inflammatory Bowel Disease Center, Sapporo Kosei General Hospital, Sapporo, Japan.
7
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
8
Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
9
Departments of Gastroenterology, Kobe City Medical Center General Hospital, Hyogo, Japan.
10
Department of Internal Medicine, Japan Red Cross Ashikaga Hospital, Tochigi, Japan.
11
Department of Gastroenterology and Hematology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
12
Inflammatory Bowel Disease Center, Fukuoka University Chikushi Hospital, Chikushino, Japan.
13
Division of Gastroenterology, Osaka City General Hospital, Osaka, Japan.
14
Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Japan.
15
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
16
Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
17
Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan.
18
Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
19
Center for Translational Research, Institute of Medical Science Hospital, University of Tokyo, Tokyo, Japan.
20
Division of Gastroenterology, Department of Medicine, Iwate Medical University, Morioka, Japan.

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

PMID:
31041545
DOI:
10.1007/s00535-019-01582-w

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