Personalized therapy for <i>Helicobacter pylori</i>: <i>CYP2C19</i> genotype effect on first‐line triple therapy

Arévalo-Galvis, Azucena; Rangel, Alba Alicia Trespalacios; Regino, William Otero

doi:10.1111/hel.12574

Cited by 13 publications

(14 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Despite the extensive literature on the impact of CYP2C19 genotypes on omeprazole pharmacokinetics, studies investigating the clinical efficacy of omeprazole with CYP2C19 rapid metabolizers (RMs) (*1/*17) and UMs (*17/*17) remain limited and were mostly carried out in non-GERD samples ( Arévalo Galvis et al, 2019 ; Chwiesko et al, 2016 ; Molina-Infante et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus

et al. 2022

View full text Add to dashboard Cite

Omeprazole is extensively used to manage gastroesophageal reflux disease (GERD). It is primarily metabolized by CYP2C19. The CYP2C19*17 (rs12248560) allele and the recently described CYP2C:TG haplotype (rs11188059 and rs2860840) are associated with increased enzymatic activity, and may reduce omeprazole exposure. This observational study aimed to investigate the association between these genetic variants and omeprazole treatment failure in GERD. We recruited predominantly New Zealand European GERD patients who either did not respond to omeprazole or experienced breakthrough heartburn symptoms despite at least 8 weeks of omeprazole (≥40 mg/day). The GerdQ score was used to gauge symptomatic severity. A total of 55 cases were recruited with a median age (range) of 56 years (19–82) and GerdQ score of 11 (5–17). Of these, 19 (34.5%) were CYP2C19*17 heterozygotes and two (3.6%) were CYP2C19*17 homozygotes. A total of 30 (27.3%) CYP2C:TG haplotypes was identified in our cohort, with seven (12.7%) CYP2C:TG homozygotes, and 16 (29%) CYP2C:TG heterozygotes. No significant differences were observed for overall CYP2C19*17 alleles, CYP2C19*17/*17, overall CYP2C:TG haplotypes, and CYP2C:TG heterozygotes (p > 0.05 for all comparisons). Gastroscopy and 24-h esophageal pH/impedance tests demonstrated objective evidence of GERD in a subgroup of 39 (71%) cases, in which the CYP2C:TG/TG was significantly enriched (p = 0.03) when compared with the haplotype frequencies in a predominantly (91%) New Zealand European reference population, but not the CYP2C19*17/*17 (p > 0.99), when compared with the allele frequencies for the non-Finnish European subset of gnomAD. We conclude that omeprazole treatment failure in GERD is associated with CYP2C:TG/TG, but not CYP2C19*17.

show abstract

Section: Discussionmentioning

confidence: 99%

Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus

et al. 2022

View full text Add to dashboard Cite

show abstract

“…En este estudio se decidió utilizar esomeprazol teniendo en cuenta la alta prevalencia en nuestro medio de metabolizadores rápidos y ultrarrápidos de IBP de primera generación (omeprazol, pantoprazol, lansoprazol), que juntos superan 80% y son una causa reconocida de fracaso terapéutico (30,36). Con este medicamento teóricamente obviaríamos una causa de fracaso terapéutico.…”

Section: Discussionunclassified

“…La capacidad de los IBPs para bloquear la producción de ácido depende de su metabolismo por la enzima CYP2C19 a nivel hepático (27)(28)(29). De acuerdo con la velocidad de inactivación o metabolismo de los IBPs existen cuatro diferentes fenotipos: metabolizadores ultrarrápidos, rápidos o extensos, intermedios y lentos (27,30). En un reciente ensayo clínico desarrollado en Colombia, se estableció que 62.4% de los sujetos son metabolizadores rápidos y 21.1% ultrarrápidos (30).…”

Section: Introductionunclassified

“…De acuerdo con la velocidad de inactivación o metabolismo de los IBPs existen cuatro diferentes fenotipos: metabolizadores ultrarrápidos, rápidos o extensos, intermedios y lentos (27,30). En un reciente ensayo clínico desarrollado en Colombia, se estableció que 62.4% de los sujetos son metabolizadores rápidos y 21.1% ultrarrápidos (30). Este hallazgo implica que para erradicar H. pylori en nuestro medio, se necesitarían dosis más altas de los IBPs dependientes de CYP (lansoprazol, omeprazol y pantoprazol) o utilizar IBPs no dependientes de CYP (Esomeprazol o rabeprazol ) (27)(28)(29) o IBPs de tercera generación bloqueadores de potasio en la ATP asa gástrica, como el vonoprazan, disponible sólo en Japón (16,31).…”

Section: Introductionunclassified

See 1 more Smart Citation

Eficacia de la terapia dual para erradicación de H. pylori en una población colombiana

2021

View full text Add to dashboard Cite

Antecedentes: Helicobacter pylori (H. pylori) afecta a 50% de la humanidad. Los tratamientos usuales han disminuido su eficacia por aumento de la resistencia a los antibióticos, excepto: amoxicilina, tetraciclina, furazolidona y bismuto. Recientemente hay un nuevo interés en la terapia dual con altas dosis de inhibidores de bomba de protones (IBP) y amoxicilina como terapia inicial y como rescate. En nuestro medio no hay estudios al respecto. Objetivo: determinar la eficacia de la terapia dual con altas dosis de IBP y amoxicilina para erradicar H. pylori. Material y métodos: estudio cuasiexperimental realizado entre diciembre de 2019 y julio de 2020 en mayores de 18 años, con H. pylori identificado histológicamente. Todos recibieron esomeprazol 40 mg media hora antes de desayuno, almuerzo y cena mas amoxicilina 1 gramo oral cada 8 horas por 14 días. La erradicación se determinó con antígenos fecales (OnSiteTM H. pylori Biotech Inc) después de cuatro semanas del tratamiento. Resultados: se incluyeron 108 pacientes, con edad promedio de 67 años, 70% mujeres. La erradicación por protocolo (PP) e intención de tratar (ITT) fue de 86% (IC95% 79.4-92.5%) para ambos. En los pacientes con tratamiento previo (26%) la eficacia fue de 85.7% (IC95% 71.8-99.5%). Los eventos adversos fueron leves en 31%, especialmente náuseas (16%) y distensión abdominal (14%). En ninguno se suspendió el tratamiento. Conclusión: la terapia dual es eficaz, fácil de administrar y con pocos efectos adversos. Sería una buena opción en nuestro medio como terapia inicial y como rescate. Se requieren estudios más grandes para verificar nuestros resultados.

show abstract

“…Genetic differences in the activity of the enzyme CYP2C19 (the homozygous EM, heterozygous EM (HetEM), and poor metabolizer) dictate how effective PPI will be. A group in Colombia found cure rates to improve from 84% to 92% in a group consisting mainly of rapid metabolisers when omeprazole doses were chosen based on the CYP2C19 polymorphism, which may be useful particularly in populations with a broad spread of CYP2C19 polymorphisms 62 …”

Section: Personalised Treatmentmentioning

confidence: 99%

Review – Treatment of Helicobacter pylori infection 2020

et al. 2020

View full text Add to dashboard Cite

This review summarizes important studies regarding Helicobacter pylori therapy published from April 2019 to April 2020. The main themes that emerge involve studies assessing antibiotic resistance, and there is also growing momentum behind the utility of vonoprazan as an alternative to proton pump inhibitor (PPI) therapy and also bismuth‐based regimens as a first‐line regimen. Antibiotic resistance is rising wherever it is being assessed, and clarithromycin resistance in particular has reached a point where it may no longer be a viable therapy without previous testing in many regions of the world. The evidence for the efficacy of a bismuth‐based quadruple therapy as a first‐line therapy is now very clearly established, and there is substantial evidence that it is the best performing first‐line therapy. The utility of vonoprazan as an alternative to PPI therapy, especially in resistant and difficult‐to‐treat groups, has also been considered in great detail this year, and it may offer an opportunity in the near future to reduce the problem of antibiotic resistance.

show abstract

Personalized therapy for Helicobacter pylori: CYP2C19 genotype effect on first‐line triple therapy

Cited by 13 publications

References 51 publications

Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus

Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at the CYP2C Locus

Eficacia de la terapia dual para erradicación de H. pylori en una población colombiana

Review – Treatment of Helicobacter pylori infection 2020

Contact Info

Product

Resources

About