Clinical relevance of innovative immunoassays for serum ustekinumab and anti-ustekinumab antibody levels in Crohn's disease

J Gastroenterol Hepatol. 2020 Jul;35(7):1163-1170. doi: 10.1111/jgh.14962. Epub 2020 Jan 12.

Abstract

Background and aim: Ustekinumab is a human monoclonal antibody to the p40 subunit of human IL-12/IL-23. The purpose of this report is to verify the newly developed immunoassays for serum ustekinumab and anti-ustekinumab antibody (AUA) concentrations and assess their clinical utility.

Methods: Serum ustekinumab trough levels and AUA levels were measured using new immunoassays in 38 patients with Crohn's disease under ustekinumab maintenance injection.

Results: Mean ustekinumab trough levels were 2.54 ± 2.1 μg/mL, and 3 of 38 patients (7.9%) were positive for AUAs. There was no association between ustekinumab trough levels and AUA levels. The optimal trough level of ustekinumab to maintain negative C-reactive protein levels (≤ 0.3 mg/dL) was 1.67 μg/mL determined by receiver operating characteristic curve analysis. Ustekinumab trough level negatively but significantly correlated with C-reactive protein, erythrocyte sedimentation rate, and Crohn's disease activity index and positively and significantly correlated with serum albumin levels. Ustekinumab trough levels were significantly higher in biologics-naïve patients than in biologics-experienced patients, although there was no difference in AUA levels.

Conclusions: We developed new assays for serum ustekinumab trough and AUA levels. These assays might provide new insights into therapeutic drug monitoring-based management of Crohn's disease patients under ustekinumab therapy.

Keywords: anti-ustekinumab antibody; therapeutic drug monitoring; ustekinumab.

MeSH terms

  • Adult
  • Antibodies / blood*
  • Biomarkers / blood
  • C-Reactive Protein
  • Crohn Disease / diagnosis*
  • Crohn Disease / drug therapy*
  • Drug Monitoring / methods*
  • Female
  • Humans
  • Immunoassay / methods*
  • Male
  • Middle Aged
  • ROC Curve
  • Serum Albumin
  • Ustekinumab / blood
  • Ustekinumab / immunology
  • Ustekinumab / therapeutic use*

Substances

  • Antibodies
  • Biomarkers
  • Serum Albumin
  • C-Reactive Protein
  • Ustekinumab