Is It Useful to Monitor Thiopurine Metabolites in Pediatric Patients with Crohn’s Disease on Combination Therapy? A Multicenter Prospective Observational Study

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61389030%3A_____%2F21%3A00549494" target="_blank" >RIV/61389030:_____/21:00549494 - isvavai.cz</a>

Alternative codes found

RIV/61989592:15310/21:73610716 RIV/00216208:11110/21:10425580 RIV/00098892:_____/21:N0000234 RIV/00064203:_____/21:10425580 and 2 more

Result on the web

<a href="http://doi.org/10.1007/s40272-021-00439-1" target="_blank" >http://doi.org/10.1007/s40272-021-00439-1</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s40272-021-00439-1" target="_blank" >10.1007/s40272-021-00439-1</a>

Result language

angličtina

Original language name

Is It Useful to Monitor Thiopurine Metabolites in Pediatric Patients with Crohn’s Disease on Combination Therapy? A Multicenter Prospective Observational Study

Original language description

Background: The additional value of azathioprine concomitant treatment on infliximab pharmacokinetics in children is not well described yet. Aims: In the present study, we aimed to describe the relationship between thiopurine metabolite levels, infliximab trough levels, anti-IFX antibody formation, and clinical and laboratory markers of disease activity in pediatric patients with Crohn’s disease, and to assess non-adherence. Methods: Data were collected prospectively during repeated visits from pediatric patients followed for Crohn’s disease in two Czech pediatric inflammatory bowel disease centers between January 2016 and June 2017. Thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine) were measured by high-performance liquid chromatography. Infliximab trough levels and anti-IFX antibody serum levels were measured routinely by ELISA. The risk of loss of response to infliximab therapy was also assessed. Results: A significant association between infliximab serum levels and 6-thioguanine erythrocyte levels was observed when tested as categorical variables (63 patients, 321 observations). To predict infliximab levels > 5 µg/mL, we propose a 6-thioguanine cutoff of 278 pmol/8 × 108 erythrocytes (sensitivity, 0.799, specificity, 0.347). A higher loss-of-response-to-infliximab rate (tested in a subgroup of 51 patients) was observed in patients with undetectable 6-thioguanine levels than in those with detectable levels (p = 0.026). Non-adherence to azathioprine therapy was suspected in 20% of patients. Conclusion: Thiopurine metabolite monitoring in pediatric patients with Crohn’s disease is useful when optimizing combination therapy. Pediatric patients with undetectable 6-thioguanine levels are more likely to lose response to infliximab therapy. When targeting optimal infliximab levels, the 6-thioguanine cutoff levels in children appear to be higher than in adults.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30402 - Technologies involving the manipulation of cells, tissues, organs or the whole organism (assisted reproduction)

Project

<a href="/en/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molecular, cellular and clinical approach to healthy ageing</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Paediatric Drugs

ISSN

1174-5878

e-ISSN

1179-2019

Volume of the periodical

23

Issue of the periodical within the volume

2

Country of publishing house

NZ - NEW ZEALAND

Number of pages

12

Pages from-to

183-194

UT code for WoS article

000627674500001

EID of the result in the Scopus database

2-s2.0-85102318056