Efficacy of proton pump inhibitors for reflux sufferers

Gastroesophageal reflux disease GERD is a chronic condition that causes serious complications. Although treatment can be quite successful, little is known about the development of symptoms during and after treatment. In a recent edition of Digestion, proton pump inhibitors (PPIs) were compared in the treatment of GERD as well as their effectiveness after treatment is stopped. PPIs are considered the best treatment for GERD, although patients tend to quickly relapse once they stop taking this medication. Pantoprazole and esomeprazole were the two medications compared in this study. This investigation found that pantoprazole and esomeprazole were very similar during treatment. However severity of symptoms and the rate of relapse were significantly lower following treatment with pantoprazole.

Gastroesophageal reflux disease (GERD) is a highly prevalent and chronic condition. The main cause is the reflux of gastric content into the oesophagus. This gives rise to a variety of symptoms such as heartburn, acid regurgitation, nausea, diarrhoea or constipation, sleep disturbances and other complaints such as respiratory symptoms. In particular, night time reflux associated with sleep disturbances significantly impairs quality of life and functionality on the following day.

The success of GERD therapy is difficult to detail as there is no link between the level of mucosal damage and the severity of symptoms. Furthermore, 70% of all patients with GERD symptoms are found to be negative for GERD after endoscopic examination. Therefore, highly successful treatment strategies should be in place that ensures high healing rates of oesophageal lesions as well as treating a broad spectrum of GERD symptoms to improve patient’s quality of life.

Proton pump inhibitors (PPI) are considered the best treatment of GERD, producing quick and successful suppression of the production of gastric acid, resulting in rapid symptom relief and high rates of oesophageal healing. Although successful, this treatment does not remove the main pathogenic factors and as such, there is a high rate of relapse after successful treatment when the intake of medication is stopped. Although this level of relapse is recognised, there is little information available about the course of GERD symptoms after the end of treatment.

A recent paper published in Digestion aimed to compare the treatment efficacy of two PPIs during treatment, as well as investigate the medication-free periods prior to and especially after cessation of active therapy. The study began with a 7-day pretreatment phase followed by a 28-day period of active treatment with either pantoprazole 40 mg or esomeprazole 40 mg once daily, followed by a 7-day posttreatment phase without medication. GERD symptoms were assessed through a validated reflux questionnaire (ReQuest^TM), a self assessed, dimension-orientated scale, allowing daily evaluation of a broad spectrum of GERD symptoms.

Patient results for this study were grouped according to the PPI taken during the treatment phase. During the pretreatment phase, the average number of episodes and number of days with GERD-related symptoms were similar between both groups. In the treatment phase, patients were assessed on their H.pylori status as well as their ReQuest score during the last 3 days of active treatment. While H. Pylori negative patients had a similar score in both groups, H.pylori positive patients in the esomeprazole group had a higher score than those in the pantoprazole group, indicating a higher symptom load.

The mean number of symptom episodes during the posttreatment phase was significantly lower in the pantoprazole group than in the esomeprazole group. Similarly, the mean number of days with GERD-related symptoms were lower in the pantoprazole group than in the esomeprazole group. The relapse rates during posttreatment were found to be 46.3% for the pantoprazole group versus 56.9% in the esomeprazole group.

This study found that both pantoprazole 40 mg once daily and esomeprazole 40 mg once daily are well tolerated and safe. Throughout the treatment period, it was found that pantoprazole was at least as effective as esomeprazole at relieving GERD-symptoms. More significantly was the discovery that during posttreatment patients treated with pantoprazole not only had significantly lower maximum symptom scores and a lower risk of relapse, but they also had fewer days of relevant GERD symptoms.

A possible explanation for the difference in results for these two medications was given which implicates their structural design. Both pantoprazole and esomeprazole are both substituted benzimidazoles. They are not identical and as such can give rise to variances in pharmacokinetic properties. Like all PPIs, they both bind to one cysteine (Cys 813), but pantoprazole binds additionally to a second cysteine (Cys 822) resulting in a more prolonged effect than other PPIs and thus an increased acid-inhibitory effect.

Reference:

1. Glatzel D, Abdel-Qader M, Gatz G. and Pfaffenberger, B. 2007. Pantoprazole 40 mg is as effective as ezomeprazole 40 mg to relieve symptoms of gastroesophageal reflux disease after 4 weeks of treatment and superior regarding the prevention of symptomatic relapse. Digestion. 75: 69-78.