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

DIAMOND study group

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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 ×108 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).

Original languageEnglish
Pages (from-to)873-882
Number of pages10
JournalAlimentary Pharmacology and Therapeutics
Volume46
Issue number9
DOIs
Publication statusPublished - 2017 Nov 1

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Crohn Disease
Anti-Idiotypic Antibodies
Pharmacokinetics
Serum
Pharmaceutical Preparations
Adalimumab
Erythrocytes

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

@article{6324348129a74005bdc69b1792490361,
title = "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",
abstract = "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 ×108 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).",
author = "{DIAMOND study group} and H. Nakase and S. Motoya and T. Matsumoto and K. Watanabe and T. Hisamatsu and N. Yoshimura and T. Ishida and S. Kato and T. Nakagawa and M. Esaki and M. Nagahori and T. Matsui and Y. Naito and T. Kanai and Y. Suzuki and M. Nojima and M. Watanabe and T. 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 Shuji Inoue and Tetsuya Ishida and Yo Ishiguro and Shunji 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",
year = "2017",
month = "11",
day = "1",
doi = "10.1111/apt.14318",
language = "English",
volume = "46",
pages = "873--882",
journal = "Alimentary Pharmacology and Therapeutics",
issn = "0269-2813",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalised pharmacokinetics in patients with Crohn's disease

T2 - a subanalysis of the DIAMOND trial

AU - DIAMOND study group

AU - Nakase, H.

AU - Motoya, S.

AU - Matsumoto, T.

AU - Watanabe, K.

AU - Hisamatsu, T.

AU - Yoshimura, N.

AU - Ishida, T.

AU - Kato, S.

AU - Nakagawa, T.

AU - Esaki, M.

AU - Nagahori, M.

AU - Matsui, T.

AU - Naito, Y.

AU - Kanai, T.

AU - Suzuki, Y.

AU - Nojima, M.

AU - Watanabe, M.

AU - Hibi, T.

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, Shuji

AU - Ishida, Tetsuya

AU - Ishiguro, Yo

AU - Ishihara, Shunji

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 - 2017/11/1

Y1 - 2017/11/1

N2 - 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 ×108 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).

AB - 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 ×108 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).

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U2 - 10.1111/apt.14318

DO - 10.1111/apt.14318

M3 - Article

VL - 46

SP - 873

EP - 882

JO - Alimentary Pharmacology and Therapeutics

JF - Alimentary Pharmacology and Therapeutics

SN - 0269-2813

IS - 9

ER -