Frazzoni M et al. (2007) Efficacy in intra-oesophageal acid suppression may decrease after 2-year continuous treatment with proton pump inhibitors. Dig Liver Dis 39: 415–421

The long-term efficacy of intra-esophageal acid suppression by continuous maintenance treatment with a PPI has been shown to decrease over time for both once and twice daily regimens, even at high doses. Long-term PPI therapy has been widely adopted for the effective management of GERD complications, including Barrett's esophagus and reflux esophagitis, but relapses have been reported in patients receiving omeprazole for the treatment of reflux esophagitis. Such relapses might result from reduced acid suppression by PPIs.

In their prospective study, Frazzoni et al. evaluated the stability of acid suppression in 45 patients with Barrett's esophagus or severe reflux esophagitis after 2 years' continuous treatment with an unmodified PPI regimen (i.e. the same regimen that normalized their initial total percentage acid exposure time [%AET]). In 27 patients, the total %AET was higher at the 2-year follow-up than at the time of normalization. The total %AET was considered abnormally high (>5.8%) in 10 patients. Overall, the median total %AET was significantly higher at the 2-year follow-up than at normalization (P = 0.029). None of the patients had heartburn at the 2-year follow-up, confirming that heartburn is not a reliable indicator of adequate intra-esophageal acid suppression.

Further long-term follow-up studies are required to determine whether reduced acid suppression by PPIs results from a partial loss of PPI antisecretory function. The authors say that such studies should assess treatment efficacy regularly to limit complications arising in patients with Barrett's esophagus or severe reflux esophagitis.