Significance of measurement of serum trough level and anti‐drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease: a subanalysis of the DIAMOND trial. Issue 9 (8th September 2017)

• Record Type: Journal Article
• Authors: Nakase, H.; Motoya, S.; Matsumoto, T.; Watanabe, K.; Hisamatsu, T.; Yoshimura, N.; Ishida, T.; Kato, S.; Nakagawa, T.; Esaki, M.; Nagahori, M.; Matsui, T.; Naito, Y.; Kanai, T.; Suzuki, Y.; Nojima, M.; Watanabe, M.; Hibi, T.
• Other Names: Andoh Akira investigator.; Ashida Toshifumi investigator.; Endo Katsuya investigator.; Endo Yutaka investigator.; Esaki Motohiro investigator.; Fujita Hiroshi investigator.; Fujiya Mikihiro investigator.; Haruma Ken investigator.; Hibi Toshifumi investigator.; Hiraoka Sakiko investigator.; Hirata Ichiro investigator.; Hisamatsu Tadakazu investigator.; Honda Yutaka investigator.; Iijima Hideki investigator.; Iizuka Bunei investigator.; Ikeya Kentaro investigator.; Inoue Takuya investigator.; Inoue Shuji investigator.; Ishida Tetsuya investigator.; Ishiguro Yo investigator.; Ishihara Shunji investigator.; Ito Hiroaki investigator.; Iwakiri Ryuichi investigator.; Kagaya Takashi investigator.; Kanai Takanori investigator.; Kashida Hiroshi investigator.; Kato Shingo investigator.; Kato Jun investigator.; Katsurada Takehiko investigator.; Kinjyo Fukunori investigator.; Kobayashi Kiyonori investigator.; Kodama Mayumi investigator.; Kunisaki Reiko investigator.; Kurahara Koichi investigator.; Kurokami Takafumi investigator.; Kyouwon Lee investigator.; Matsuda Koichiro investigator.; Matsueda Kazuhiro investigator.; Matsui Toshiyuki investigator.; Matsumoto Takayuki investigator.; Mitsuyama Keiichi investigator.; Mizokami Yuji investigator.; Motoya Satoshi investigator.; Naito Yuji investigator.; Nakagawa Tomoo investigator.; Nakamura Shiro investigator.; Nakase Hiroshi investigator.; Nojima Masanori investigator.; Nomura Masafumi investigator.; Ogawa Atsuhiro investigator.; Okazaki Kazuichi investigator.; Otsuka Kazuaki investigator.; Sakuraba Hirotake investigator.; Saruta Masayuki investigator.; Sasaki Makoto investigator.; Shirai Takayuki investigator.; Suga Tomoaki investigator.; Sugimura Kazuhito investigator.; Sugiyama Toshiro investigator.; Suzuki Yasuo investigator.; Takeshima Fuminao investigator.; Tamaki Hiroyuki investigator.; Tanaka Shinji investigator.; Tanida Satoshi investigator.; Tominaga Keiichi investigator.; Tomizawa Taku investigator.; Watanabe Kenji investigator.; Watanabe Mamoru investigator.; Yamamoto Shojiro investigator.; Yamashita Masaki investigator.; Yoshida Atsushi investigator.; Yoshimura Naoki investigator.;
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 46:Issue 9(2017)
• Page Start: 873
• Page End: 882
• Publication Date: 2017-09-08
• Subjects: Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.14318
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Significance of monitoring adalimumab trough levels and anti‐adalimumab antibodies (AAA) for disease outcome in Crohn's disease (CD) patients remained unclear. Aim: To evaluate the association of adalimumab trough levels and AAA at week 26 with clinical remission at week 52, the effect of azathiopurine on AAA and factors influencing trough levels in CD patients in the DIAMOND trial. Methods: We performed this study using adalimumab trough levels, AAA at week 26 and 6‐thioguanine nucleotide (TGN) in red blood cells at week 12. A multiple regression model and receiver operating analysis was performed to identify factors influencing adalimumab trough levels and AAA, and adalimumab thresholds for predicting disease activity. Results: There was a significant difference of adalimumab trough level at week 26 between patients with disease remission and without at week 52 (7.7 ± 3.3 μg/mL vs 5.4 ± 4.3 μg/mL: P <.001). Adalimumab trough level of 5.0 μg/mL yielded optimal sensitivity and specificity for remission prediction (80.2% and 55.6%, respectively). AAA development at week 26 significantly affected remission at week 52 ( P = .021), which was strongly associated with adalimumab trough levels. Female gender and increasing body weight were independently associated with low adalimumab trough levels, and female gender was associated with AAA development. A cut‐off 6TGN level of >222.5 p mol/8 ×10 8 RBCs yielded sensitivity (100%) and specificity (60.6%) for AAA negativity. Conclusion: Adalimumab trough levels and AAA occurrence were significantly associated with clinical remission. Higher 6TGN affected AAA negativity. The combination therapy is beneficial in some relevant aspects for CD patients. (UMIN Registration No. 000005146) Abstract : Linked Content This article is linked to Domènech et al and Nakase papers. To view these papers visithttps://doi.org/10.1111/apt.14350 andhttps://doi.org/10.1111/apt.14365 .