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.

• Authors: Kenji Watanabe, Takayuki Matsumoto, Tadakazu Hisamatsu, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi, DIAMOND study group
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 16 Issue 4 Pg. 542-549.e1 (04 2018) ISSN: 1542-7714 [Electronic] United States
• PMID: 29104132 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Adalimumab
• Azathioprine

Topics

• Adalimumab (administration & dosage, pharmacokinetics)
• Adolescent
• Adult
• Aged
• Anti-Inflammatory Agents (administration & dosage, pharmacokinetics)
• Azathioprine (administration & dosage)
• Crohn Disease (drug therapy)
• Drug Therapy, Combination
• Endoscopy
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Intestinal Mucosa (pathology)
• Japan
• Male
• Middle Aged
• Plasma (chemistry)
• Prospective Studies
• Treatment Outcome
• Young Adult