A multicentre randomised trial to compare the efficacy of omeprazole versus rabeprazole in early symptom relief in patients with reflux esophagitis

Abstract

Background: Proton pump inhibitors (PPIs) are affected by cytochrome P450 2C19 (CYP2C19) polymorphisms. This study compared the effect of two PPIs on early symptom relief in Japanese patients with reflux esophagitis, classified by the CYP2C19 phenotype.

Methods: Patients with reflux esophagitis were randomised to treatment with omeprazole 20 mg or rabeprazole 10 mg once daily. The CYP2C19 phenotype [homozygous extensive metaboliser (homoEM), heterozygous extensive metaboliser (heteroEM) or poor metaboliser (PM)] of each patient was determined. The primary efficacy endpoint was early, sufficient (Global Overall Symptom scale score 1 or 2), sustained (maintained for ≥7 days) reflux symptom relief.

Results: Of the 199 patients included in this analysis, the proportion achieving sufficient, sustained reflux symptom relief was higher with omeprazole than with rabeprazole on day 1 (35.6 vs. 22.4%; p = 0.041) and day 2 (43.6 vs. 28.6%; p = 0.028); there was no significant difference between the two groups on days 3-7. Among patients with the CYP2C19 PM phenotype, sufficient, sustained reflux symptom relief was higher with omeprazole than with rabeprazole on days 4-7 (62.5-66.9 vs. 31.6%; p ≤ 0.03); differences were not significant on days 1-3, or among those with the homoEM or heteroEM phenotypes on days 1-7.

Conclusions: In Japanese patients with reflux esophagitis, omeprazole 20 mg is more effective than rabeprazole 10 mg at achieving early, sufficient, sustained reflux symptom relief in individuals with the CYP2C19 PM phenotype, and is similarly effective to rabeprazole 10 mg in those with heteroEM or homoEM phenotypes.

Fig. 1

Overview of study design. GOS Global Overall Symptom

Fig. 2

Proportion of patients achieving sustained and sufficient relief of their reflux symptoms on days 1–7 of therapy with omeprazole 20 mg or rabeprazole 10 mg. Sustained and sufficient symptom relief was defined as a GOS scale score of 1 or 2 that was maintained for at least 7 consecutive days. GOS Global Overall Symptom

Fig. 3

Proportion of patients achieving sustained and sufficient relief of their reflux symptoms on days 1–7 of therapy with omeprazole 20 mg or rabeprazole 10 mg in those with the CYP2C19 phenotype a PM, b heteroEM and c homoEM. Sustained and sufficient symptom relief was defined as a GOS scale score of 1 or 2 that was maintained for at least 7 consecutive days. CYP2C19 phenotype was unknown for two patients in the omeprazole group. CYP2C19 cytochrome P450 2C19, GOS Global Overall Symptom, heteroEM hetero extensive metaboliser, homoEM homo extensive metaboliser, PM poor metaboliser

Fig. 4

Proportion of patients achieving sufficient relief of their reflux symptoms (GOS scale score of 1 or 2) after 2 and 4 weeks of therapy with omeprazole 20 mg or rabeprazole 10 mg a overall and b according to CYP2C19 phenotype. CYP2C19 phenotype was unknown for two patients in the omeprazole group. CYP2C19 cytochrome P450 2C19, GOS Global Overall Symptom, heteroEM hetero extensive metaboliser, homoEM homo extensive metaboliser, PM poor metaboliser

Fig. 5

Proportion of patients achieving complete resolution (GOS scale score of 1) of their reflux symptoms after 2 and 4 weeks of therapy with omeprazole 20 mg or rabeprazole 10 mg a overall and b according to CYP2C19 phenotype. CYP2C19 phenotype was unknown for two patients in the omeprazole group. CYP2C19 cytochrome P450 2C19, GOS Global Overall Symptom, heteroEM hetero extensive metaboliser, homoEM homo extensive metaboliser, PM poor metaboliser

Fig. 6

Proportion of patients achieving sufficient relief (GOS scale score of 1 or 2) of their upper gastrointestinal symptoms after 2 and 4 weeks of therapy with omeprazole 20 mg or rabeprazole 10 mg a overall and b according to CYP2C19 phenotype. CYP2C19 phenotype was unknown for two patients in the omeprazole group. CYP2C19 cytochrome P450 2C19, GOS Global Overall Symptom, heteroEM hetero extensive metaboliser, homoEM homo extensive metaboliser, PM poor metaboliser

Fig. 7

Proportion of patients achieving complete resolution (GOS scale score of 1) of their upper gastrointestinal symptoms after 2 and 4 weeks of therapy with omeprazole 20 mg or rabeprazole 10 mg a overall and b according to CYP2C19 phenotype was unknown for two patients in the omeprazole group. CYP2C19 cytochrome P450 2C19, GOS Global Overall Symptom, heteroEM hetero extensive metaboliser, homoEM homo extensive metaboliser, PM poor metaboliser