TY - JOUR
T1 - Clinical relevance of innovative immunoassays for serum ustekinumab and anti-ustekinumab antibody levels in Crohn's disease
AU - Morita, Yasuhiro
AU - Imai, Takayuki
AU - Bamba, Shigeki
AU - Takahashi, Kenichiro
AU - Inatomi, Osamu
AU - Miyazaki, Takako
AU - Watanabe, Kenji
AU - Nakamura, Shiro
AU - Yoshida, Atsushi
AU - Endo, Yutaka
AU - Ohmiya, Naoki
AU - Tsujikawa, Tomoyuki
AU - Andoh, Akira
N1 - Publisher Copyright:
© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
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U2 - 10.1111/jgh.14962
DO - 10.1111/jgh.14962
M3 - Article
C2 - 31860733
AN - SCOPUS:85078629701
SN - 0815-9319
VL - 35
SP - 1163
EP - 1170
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 7
ER -