Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study]

被引：13

作者：

Hisamatsu, Tadakazu ^{[1
,29
]}

Matsumoto, Takayuki ^{[2
,57
]}

Watanabe, Kenji ^{[3
,63
,84
]}

Nakase, Hiroshi ^{[4
,64
]}

Motoya, Satoshi ^{[5
,60
]}

Yoshimura, Naoki ^{[6
,89
]}

Ishida, Tetsuya ^{[7
,36
]}

Kato, Shingo ^{[8
,44
]}

Nakagawa, Tomoo ^{[9
,62
]}

Esaki, Motohiro ^{[10
,22
]}

Nagahori, Masakazu ^{[11
]}

Matsui, Toshiyuki ^{[12
,56
]}

Naito, Yuji ^{[13
,61
]}

Kanai, Takanori ^{[14
,42
]}

Suzuki, Yasuo ^{[15
,77
]}

Nojima, Masanori ^{[16
,65
]}

Watanabe, Mamoru ^{[11
,85
]}

Hibi, Toshifumi ^{[17
,26
]}

Andoh, Akira ^{[18
]}

Ashida, Toshifumi ^{[19
]}

Endo, Katsuya ^{[20
]}

Endo, Yutaka ^{[21
]}

Esaki, Motohiro ^{[10
,22
]}

Fujita, Hiroshi ^{[23
]}

Fujiya, Mikihiro ^{[24
]}

Haruma, Ken ^{[25
]}

Hibi, Toshifumi ^{[17
,26
]}

Hiraoka, Sakiko ^{[27
]}

Hirata, Ichiro ^{[28
]}

Hisamatsu, Tadakazu ^{[1
,29
]}

Honda, Yutaka ^{[30
]}

Iijima, Hideki ^{[31
]}

Iizuka, Bunei ^{[32
]}

Ikeya, Kentaro ^{[33
]}

Inoue, Takuya ^{[34
]}

Inoue, Syuji ^{[35
]}

Ishida, Tetsuya ^{[7
,36
]}

Ishiguro, Yo ^{[37
]}

Ishihara, Shunji ^{[38
]}

Ito, Hiroaki ^{[39
]}

Iwakiri, Ryuichi ^{[40
]}

Kagaya, Takashi ^{[41
]}

Kanai, Takanori ^{[14
,42
]}

Kashida, Hiroshi ^{[43
]}

Kato, Shingo ^{[8
,44
]}

Kato, Jun ^{[45
]}

Katsurada, Takehiko ^{[46
]}

Kinjyo, Fukunori ^{[47
]}

Kobayashi, Kiyonori ^{[48
]}

Kodama, Mayumi ^{[49
]}

机构：

[1] Kyorin Univ, Dept Internal Med 3, Sch Med, Tokyo, Japan

[2] Iwate Med Univ, Dept Med, Div Gastroenterol, Morioka, Iwate, Japan

[3] Hyogo Coll Med, Dept Intestinal Inflammat Res, Nishinomiya, Hyogo, Japan

[4] Sapporo Med Univ, Dept Gastroenterol & Hepatol, Sch Med, Sapporo, Hokkaido, Japan

[5] Sapporo Kosei Gen Hosp, Inflammatory Bowel Dis Ctr, Sapporo, Hokkaido, Japan

[6] Tokyo Yamate Med Ctr, Div Gastroenterol, Dept Med, Tokyo, Japan

[7] Ishida Clin IBD & Gastroenterol, Oita, Japan

[8] Saitama Med Univ, Dept Gastroenterol & Hepatol, Saitama Med Ctr, Saitama, Japan

[9] Chiba Univ, Grad Sch Med, Dept Gastroenterol & Nephrol, Chiba, Japan

[10] Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan

[11] Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Tokyo, Japan

[12] Fukuoka Univ, Dept Gastroenterol, Chikushi Hosp, Chikushino, Japan

[13] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Mol Gastroenterol & Hepatol, Kyoto, Japan

[14] Keio Univ, Sch Med, Dept Internal Med, Tokyo, Japan

[15] Toho Univ, Dept Internal Med, Sakura Med Ctr, Sakura, Chiba, Japan

[16] Univ Tokyo, Inst Med Sci Hosp, Ctr Translat Res, Tokyo, Japan

[17] Kitasato Univ, Ctr Adv IBD Res & Treatment, Kitasato Inst Hosp, Tokyo, Japan

[18] Shiga Univ Med Sci, Otsu, Shiga, Japan

[19] Sapporo Higashi Tokushukai Hosp, Sapporo, Hokkaido, Japan

[20] Tohoku Univ, Sendai, Miyagi, Japan

[21] Showa Univ, Fujigaoka Hosp, Tokyo, Japan

[22] Kyushu Univ, Fukuoka, Fukuoka, Japan

[23] Kagoshima Univ, Kagoshima, Japan

[24] Asahikawa Med Univ, Asahikawa, Hokkaido, Japan

[25] Kawasaki Med Sch, Kawasaki, Kanagawa, Japan

[26] Kitasato Univ, Kitasato Inst Hosp, Tokyo, Japan

[27] Okayama Univ, Okayama, Japan

[28] Fujita Hlth Univ Hosp, Toyoake, Aichi, Japan

[29] Kyorin Univ, Sch Med, Mitaka, Tokyo, Japan

[30] Niigata Univ, Niigata, Japan

[31] Osaka Univ, Suita, Osaka, Japan

[32] Tokyo Womens Med Univ, Tokyo, Japan

[33] Hamamatsu South Hosp, Hamamatsu, Shizuoka, Japan

[34] Osaka Med Coll, Takatsuki, Osaka, Japan

[35] Kochi Natl Hosp, Kochi, Japan

[36] Oita Red Cross Hosp, Oita, Japan

[37] Hirosaki Natl Hosp, Hirosaki, Aomori, Japan

[38] Shimane Univ, Matsue, Shimane, Japan

[39] Kinshukai Infus Clin, Osaka, Japan

[40] Saga Univ, Saga, Japan

[41] Kanazawa Univ, Kanazawa, Ishikawa, Japan

[42] Keio Univ, Tokyo, Japan

[43] Kinki Univ, Higashiosaka, Osaka, Japan

[44] Saitama Med Univ, Saitama Med Ctr, Saitama, Japan

[45] Wakayama Med Univ, Wakayama, Japan

[46] Hokkaido Univ, Sapporo, Hokkaido, Japan

[47] Univ Ryukyus, Nishihara, Okinawa, Japan

[48] Kitasato Univ, Tokyo, Japan

[49] Miyazaki Med Ctr Hosp, Miyazaki, Japan

[50] Yokohama City Univ, Med Ctr, Yokohama, Kanagawa, Japan

来源：

JOURNAL OF CROHNS & COLITIS | 2019年 / 13卷 / 09期

关键词：

Adalimumab; Crohn's disease; anti-TNF-alpha antibody; thiopurine; COMBINATION THERAPY; PHARMACOKINETICS; 6-THIOGUANINE; MONOTHERAPY; INDEX;

D O I：

10.1093/ecco-jcc/jjz030

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background: Combining a thiopurine with the human anti-tumour necrosis factor-a monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. Methods: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. Results: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. Conclusions: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

引用

页码：1097 / 1104

页数：8

共 50 条

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