Inosine Triphosphate Pyrophosphatase and NUDT15 are Good Predictors of Clinical Outcomes in Thiopurine-Treated Chinese Patients with Inflammatory Bowel Disease.
Ther Drug Monit
; 44(3): 391-395, 2022 06 01.
Article
em En
| MEDLINE
| ID: mdl-35067667
ABSTRACT
BACKGROUND:
Although the relationship between NUDT15 and thiopurine-induced leukopenia has been proven in previous studies, no prominent factors explaining interindividual variations in its active metabolite, 6-thioguanine nucleotide (6-TGN), and clinical efficacy have been identified. In this study, the correlation between genotypes (thiopurine S-methyltransferase, NUDT15, and ITPA polymorphisms), 6-TGN concentrations, and clinical outcomes (efficacy and side effects) in patients with inflammatory bowel disease were investigated.METHODS:
In total, 160 patients with inflammatory bowel disease were included, and the 3 genotyped genes and 6-TGN levels were measured by high-performance liquid chromatography. Statistical analyses and calculations were performed to determine their relationships.RESULTS:
ITPA genotypes and 6-TGN concentration were both associated with the clinical effectiveness of azathioprine (P = 0.036 and P = 4.6 × 10-7), with a significant correlation also detected between them (P = 0.042). Patients with ITPA variant alleles exhibited higher 6-TGN levels than those with the wild-type allele. In addition, the relationship between NUDT15 and leukopenia and neutropenia was confirmed (P = 1.79 × 10-7 and 0.002).CONCLUSIONS:
In summary, it is recommended that both ITPA and NUDT15 genotyping should be performed before azathioprine initiation. Moreover, the 6-TGN concentration should be routinely monitored during the later period of treatment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirofosfatases
/
Doenças Inflamatórias Intestinais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
País/Região como assunto:
Asia
Idioma:
En
Revista:
Ther Drug Monit
Ano de publicação:
2022
Tipo de documento:
Article