Predictors of Reflux Esophagitis Healing
We performed a post hoc analysis of a large, randomised trial of AZD0865 (a potassium-competitive acid blocker) 25–75 mg/day vs. esomeprazole 40 mg/day (present as 44.5 mg/day esomeprazole magnesium trihydrate) for up to 4 or up to 8 weeks for the treatment of RO (N = 1514) (clinicaltrials.gov identifier: NCT00206245). Endoscopy was performed at baseline; patients included in the clinical trial had LA grade A–D RO, a minimum 6-month history of heartburn ('burning feeling behind the breastbone') as their main GERD symptom, and had experienced ≥4 days of at least moderate intensity heartburn in the week before randomisation, as measured by the Reflux Disease Questionnaire (RDQ) with a 7-day recall.
Most (93%) of the patients also had concomitant regurgitation of some frequency or intensity at baseline. Patients with dominant dyspeptic RDQ symptoms were excluded from the trial. The original trial's primary endpoint was healing of RO at 4 weeks, although healing rates at 2 and 8 weeks were also assessed as secondary variables. To accomplish this while minimising the number of endoscopies performed on each patient, the study population was randomly divided into groups A and B, which were of similar size. Group A patients had endoscopy planned at weeks 2 and 4 and group B at weeks 4 and 8. All patients completed the RDQ by electronic diary twice daily during the first 4 weeks of treatment and the Quality Of Life in Reflux Disease and Dyspepsia (QOLRAD) questionnaire at baseline, after 4 weeks (group A only), and after 8 weeks (group B only) of treatment. Higher scores on the 1–7 graded Likert scale indicate better HRQoL.
Patients in group A (n = 767) were assigned treatment for up to 4 weeks. Therapy was stopped after 2 weeks in patients whose RO had healed. Patients in group B (n = 747) were assigned treatment for up to 8 weeks. Therapy was stopped after 4 weeks in patients whose RO had healed. No more endoscopies or other types of follow-up were done in patients after their RO had healed.
As there was no significant difference between esomeprazole and the various doses of AZD0865 with respect to either the response of heartburn or the healing of RO, we pooled data for all treatment arms in the analysis. Healing of RO in group A was categorised as 'rapid' (RO had healed at 2 weeks) or unhealed at 2 weeks. Healing of RO in group B was categorised as 'slow' (RO not healed at 4 weeks but healed at 8 weeks) or 'refractory' (RO not healed at 8 weeks). Patients in group B who were healed at 4 weeks would also include unidentified 'rapid healers' as they did not have endoscopy at 2 weeks. Patients in group B who were healed at 4 weeks were therefore not included in the analysis.
Proportions were compared by χ tests. For age, the mean values were compared by t-tests. P-values below 0.05 were considered statistically significant.
Variables with more than two categories were collapsed into two categories for comparison (e.g. the proportion of patients with LA grade A + B was compared between groups). Independent predictors of RO healing rate were evaluated by logistic regression analysis.
Methods
We performed a post hoc analysis of a large, randomised trial of AZD0865 (a potassium-competitive acid blocker) 25–75 mg/day vs. esomeprazole 40 mg/day (present as 44.5 mg/day esomeprazole magnesium trihydrate) for up to 4 or up to 8 weeks for the treatment of RO (N = 1514) (clinicaltrials.gov identifier: NCT00206245). Endoscopy was performed at baseline; patients included in the clinical trial had LA grade A–D RO, a minimum 6-month history of heartburn ('burning feeling behind the breastbone') as their main GERD symptom, and had experienced ≥4 days of at least moderate intensity heartburn in the week before randomisation, as measured by the Reflux Disease Questionnaire (RDQ) with a 7-day recall.
Most (93%) of the patients also had concomitant regurgitation of some frequency or intensity at baseline. Patients with dominant dyspeptic RDQ symptoms were excluded from the trial. The original trial's primary endpoint was healing of RO at 4 weeks, although healing rates at 2 and 8 weeks were also assessed as secondary variables. To accomplish this while minimising the number of endoscopies performed on each patient, the study population was randomly divided into groups A and B, which were of similar size. Group A patients had endoscopy planned at weeks 2 and 4 and group B at weeks 4 and 8. All patients completed the RDQ by electronic diary twice daily during the first 4 weeks of treatment and the Quality Of Life in Reflux Disease and Dyspepsia (QOLRAD) questionnaire at baseline, after 4 weeks (group A only), and after 8 weeks (group B only) of treatment. Higher scores on the 1–7 graded Likert scale indicate better HRQoL.
Patients in group A (n = 767) were assigned treatment for up to 4 weeks. Therapy was stopped after 2 weeks in patients whose RO had healed. Patients in group B (n = 747) were assigned treatment for up to 8 weeks. Therapy was stopped after 4 weeks in patients whose RO had healed. No more endoscopies or other types of follow-up were done in patients after their RO had healed.
As there was no significant difference between esomeprazole and the various doses of AZD0865 with respect to either the response of heartburn or the healing of RO, we pooled data for all treatment arms in the analysis. Healing of RO in group A was categorised as 'rapid' (RO had healed at 2 weeks) or unhealed at 2 weeks. Healing of RO in group B was categorised as 'slow' (RO not healed at 4 weeks but healed at 8 weeks) or 'refractory' (RO not healed at 8 weeks). Patients in group B who were healed at 4 weeks would also include unidentified 'rapid healers' as they did not have endoscopy at 2 weeks. Patients in group B who were healed at 4 weeks were therefore not included in the analysis.
Statistical Analysis
Proportions were compared by χ tests. For age, the mean values were compared by t-tests. P-values below 0.05 were considered statistically significant.
Variables with more than two categories were collapsed into two categories for comparison (e.g. the proportion of patients with LA grade A + B was compared between groups). Independent predictors of RO healing rate were evaluated by logistic regression analysis.
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