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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/61989592:15310/21:73610716 RIV/00216208:11110/21:10425580 RIV/00098892:_____/21:N0000234 RIV/00064203:_____/21:10425580 a 2 dalších

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

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

Projekt

<a href="/cs/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molekulární, buněčný a klinický přístup ke zdravému stárnutí</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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

Název periodika

Paediatric Drugs

ISSN

1174-5878

e-ISSN

1179-2019

Svazek periodika

23

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

NZ - Nový Zéland

Počet stran výsledku

12

Strana od-do

183-194

Kód UT WoS článku

000627674500001

EID výsledku v databázi Scopus

2-s2.0-85102318056