Prognostic factors influencing relapse of oesophagitis during maintenance therapy with antisecretory drugs: A meta-analysis of long-term omeprazole trials

Background: This meta-analysis investigated factors that may affect the risk of relapse of oesophagitis, and evaluated the predictive value of symptoms for the presence of relapse during long-term treatment. Methods: Individual data from 1154 patients included in five independently conducted, randomized, long-term clinical trials of the efficacy of different dosage regimens of omeprazole, standard ranitidine treatment and placebo for the prevention of relapse of oesophagitis were pooled for this meta-analysis. The therapeutic regimens studied were omeprazole 20 mg o.m. (OME20) in 366 patients, omeprazole 10 mg o.m. (OME10) in 225 patients, omeprazole 20 mg weekends (OMEW) in 235 patients, ranitidine 150 mg b.d. (RAN) in 179 patients, or placebo (PLA) in 149 patients. Results: OME20 maintained 82.4% (95% CI: 78.2-86.6%) of patients in endoscopic remission over the 6-month period compared to 71.9% (95% CI: 65.5-78.3%) for OME10, 52.3% (95% CI: 44.4-60.1%) for RAN, 42.7% (95% CI: 35.8-49.5%) for OMEW, and 10.6% (95% CI: 5.0-16.3%) for PLA. A Cox's regression analysis of time to recurrence of oesophagitis showed that four factors were associated with a higher relapse rate during placebo and active maintenance therapy: (a) pre-treatment severity of oesophagitis (P < 0.0001), (b) young age (P = 0.01), (c) non-smoking (P = 0.02) and (d) moderate/severe regurgitation before entry into the trials (P = 0.03). Asymptomatic relapse of oesophagitis was uncommon, being found in only 8.6% of the patients. Conclusions: Maintenance treatment with omeprazole 10 and 20 mg daily is superior to all other regimens tested, and is only marginally influenced by the pretreatment severity of oesophagitis. Age contributes to the factors that influence the outcome during long-term treatment with omeprazole. Symptom relief is highly predictive for the maintenance of healing.