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 journalArticlepeer-review

34 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

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)

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