Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease

DIAMOND study group

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background & Aims: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend =.001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P <.001). Conclusions: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

Original languageEnglish
Pages (from-to)542-549.e1
JournalClinical Gastroenterology and Hepatology
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 1 2018

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Crohn Disease
Pharmacokinetics
Odds Ratio
Confidence Intervals
Azathioprine
Randomized Controlled Trials
Adalimumab
Biological Products
Japan
Referral and Consultation

Keywords

  • Crohn's Disease Activity Index
  • DIAMOND Trial
  • Ileocolonoscopy
  • Narrowing

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease. / DIAMOND study group.

In: Clinical Gastroenterology and Hepatology, Vol. 16, No. 4, 01.04.2018, p. 542-549.e1.

Research output: Contribution to journalArticle

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title = "Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease",
abstract = "Background & Aims: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95{\%} confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95{\%} CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95{\%} CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95{\%} CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95{\%} CI, 1.14–1.58; P for trend =.001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P <.001). Conclusions: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.",
keywords = "Crohn's Disease Activity Index, DIAMOND Trial, Ileocolonoscopy, Narrowing",
author = "{DIAMOND study group} and Kenji Watanabe and Takayuki Matsumoto and Tadakazu Hisamatsu and Hiroshi Nakase and Satoshi Motoya and Naoki Yoshimura and Tetsuya Ishida and Shingo Kato and Tomoo Nakagawa and Motohiro Esaki and Masakazu Nagahori and Toshiyuki Matsui and Yuji Naito and Takanori Kanai and Yasuo Suzuki and Masanori Nojima and Mamoru Watanabe and Toshifumi Hibi and Akira Andoh and Toshifumi Ashida and Katsuya Endo and Yutaka Endo and Motohiro Esaki and Hiroshi Fujita and Mikihiro Fujiya and Ken Haruma and Toshifumi Hibi and Sakiko Hiraoka and Ichiro Hirata and Tadakazu Hisamatsu and Yutaka Honda and Hideki Iijima and Bunei Iizuka and Kentaro Ikeya and Takuya Inoue and Syuji Inoue and Tetsuya Ishida and Yo Ishiguro and Shyunji Ishihara and Hiroaki Ito and Ryuichi Iwakiri and Takashi Kagaya and Takanori Kanai and Hiroshi Kashida and Shingo Kato and Jun Kato and Takehiko Katsurada and Fukunori Kinjyo and Kiyonori Kobayashi and Mayumi Kodama",
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TY - JOUR

T1 - Clinical and Pharmacokinetic Factors Associated With Adalimumab-Induced Mucosal Healing in Patients With Crohn's Disease

AU - DIAMOND study group

AU - Watanabe, Kenji

AU - Matsumoto, Takayuki

AU - Hisamatsu, Tadakazu

AU - Nakase, Hiroshi

AU - Motoya, Satoshi

AU - Yoshimura, Naoki

AU - Ishida, Tetsuya

AU - Kato, Shingo

AU - Nakagawa, Tomoo

AU - Esaki, Motohiro

AU - Nagahori, Masakazu

AU - Matsui, Toshiyuki

AU - Naito, Yuji

AU - Kanai, Takanori

AU - Suzuki, Yasuo

AU - Nojima, Masanori

AU - Watanabe, Mamoru

AU - Hibi, Toshifumi

AU - Andoh, Akira

AU - Ashida, Toshifumi

AU - Endo, Katsuya

AU - Endo, Yutaka

AU - Esaki, Motohiro

AU - Fujita, Hiroshi

AU - Fujiya, Mikihiro

AU - Haruma, Ken

AU - Hibi, Toshifumi

AU - Hiraoka, Sakiko

AU - Hirata, Ichiro

AU - Hisamatsu, Tadakazu

AU - Honda, Yutaka

AU - Iijima, Hideki

AU - Iizuka, Bunei

AU - Ikeya, Kentaro

AU - Inoue, Takuya

AU - Inoue, Syuji

AU - Ishida, Tetsuya

AU - Ishiguro, Yo

AU - Ishihara, Shyunji

AU - Ito, Hiroaki

AU - Iwakiri, Ryuichi

AU - Kagaya, Takashi

AU - Kanai, Takanori

AU - Kashida, Hiroshi

AU - Kato, Shingo

AU - Kato, Jun

AU - Katsurada, Takehiko

AU - Kinjyo, Fukunori

AU - Kobayashi, Kiyonori

AU - Kodama, Mayumi

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Background & Aims: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend =.001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P <.001). Conclusions: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

AB - Background & Aims: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy versus combination with azathioprine for patients with Crohn's disease (CD) who were naive to biologics and thiopurines. We performed a subanalysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. Methods: We compared simple endoscopic scores for CD between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n = 85) or adalimumab in combination with azathioprine (n = 91), from June 2011 to June 2014 in Japan. We evaluated associations of simple endoscopic scores for CD with clinical factors and trough levels of adalimumab. Ultimately, 135 patients at Week 26 and 139 patients at Week 52 from 44 referral sites were analyzed for the present investigation. Results: The odds for endoscopic response were significantly higher in the combination group than in the monotherapy group at Week 26 (odds ratio [OR], 2.12; 95% confidence interval [CI], 1.04–4.32) but not at Week 52 (OR, 1.50; 95% CI, 0.77–2.94). The odds of mucosal healing did not differ significantly between groups at Weeks 26 or 52. Simple endoscopic scores for CD at Week 0 was significantly associated with mucosal healing at Week 26 (OR, 0.80; 95% CI, 0.72–0.90) and at Week 52 (OR, 0.91; 95% CI, 0.84–0.99). Higher adalimumab trough level at Week 26 associated with mucosal healing at Week 52 (OR, 1.34; 95% CI, 1.14–1.58; P for trend =.001) and was significantly higher in patients with endoscopic response than in patients without endoscopic response at Weeks 26 and 52 (P <.001). Conclusions: In a post hoc analysis of data from a randomized controlled trial of patients with moderate to severe CD, we found that adalimumab in combination with azathioprine increased trough levels of adalimumab. Higher trough levels of adalimumab associated with endoscopic response and mucosal healing at Weeks 26 and 52. UMIN registration No: 000005146.

KW - Crohn's Disease Activity Index

KW - DIAMOND Trial

KW - Ileocolonoscopy

KW - Narrowing

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JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

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