Efficacy and Tolerability of Pantoprazole Compared with Misoprostol for the Prevention of NSAID-Related Gastrointestinal Lesions and Symptoms in Rheumatic Patients

Abstract

Aim: To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 µg twice daily (b.i.d.), administered for 6 months to rheumatic patients who required long-term therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) and who were at increased risk of developing gastrointestinal lesions. Methods: This randomized, double-blind, multicenter, parallel group comparison study was performed with rheumatic patients (n = 515) who were likely to take NSAIDs continuously for at least 6 months. Patients were 55 years or older, at risk to develop gastrointestinal lesions, had less than five erosions/petechiae in the stomach and duodenum, no ulcers, no reflux esophagitis (endoscopy-proven), and gastrointestinal symptoms of at most moderate intensity. A minimum daily dose was defined for NSAIDs (COX-2 inhibitors were not available at the time). Patients were randomized to take either pantoprazole 20 mg o.d. (n = 257) or misoprostol 200 µg b.i.d. (n = 258) for 6 months while continuing NSAID therapy. Endoscopy was performed at baseline, 3, and 6 months. Results: Pantoprazole was superior to misoprostol (p < 0.001) with regard to ‘therapeutic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, reflux esophagitis, severe gastrointestinal symptoms, and/or ‘likely’ or ‘definitely’ related adverse event leading to study termination). Estimated remission rates at 3 and 6 months (Kaplan-Meier life-table analysis) were, respectively, 93 and 89% (pantoprazole) and 79 and 70% (misoprostol). Pantoprazole was superior to misoprostol (p = 0.005) with regard to ‘endoscopic failure’ (occurrence of a peptic ulcer, ten or more erosions/petechiae in the stomach/duodenum, or reflux esophagitis) after 6 months. Estimated remission rates at 3 and 6 months were, respectively, 98 and 95% (pantoprazole) and 95 and 86% (misoprostol). Patients discontinuing the study early due to adverse events ‘likely’ or ‘definitely’ related to the study drug accounted for 13/257 (5%) in the pantoprazole and 33/258 (13%) in the misoprostol treatment groups. Conclusion: Pantoprazole 20 mg o.d. is superior to misoprostol 200 µg b.i.d. in the prevention of NSAID-induced gastrointestinal lesions and symptoms in patients on continuous long-term treatment with NSAIDs due to rheumatic diseases and at risk to develop such lesions or symptoms.

Improvement of Non-Steroidal Anti-Inflammatory Drug-Induced Gastrointestinal Symptoms during Proton Pump Inhibitor Treatment: Are G-Protein β3 Subunit Genotype, Helicobacter pylori Status, and Environmental Factors Response Modifiers?

“…Our data on pantoprazole are consistent with other studies indicating that PPIs are efficacious in reducing NSAID-induced mucosal lesions and complications [2,15]. Two identical trials on the efficacy of esomeprazole 20 and 40 mg once daily for the relief of upper GI symptoms in patients using NSAIDs were recently published showing a consistent trend for higher efficacy with the lower dose [16].…”

Intragastric acid control in non‐steroidal anti‐inflammatory drug users: comparison of esomeprazole, lansoprazole and pantoprazole

“…3 Control of gastric acidity using acid-suppressive therapy has been proposed as an effective means of healing ulcers [6][7][8][9][10][11] and controlling and preventing NSAID-associated upper GI injury and ulcer complications. 8,9,[12][13][14][15][16] Although both H 2 RAs and PPIs can be used as acid-suppressive agents in the treatment of other disease states, PPIs are preferable to standard doses of H 2 RAs for preventing NSAID-associated endoscopic injury. 9,20 Results of recent studies have shown that esomeprazole treatment significantly decreased the development of ulcers associated with the use of COX-2-selective and non-selective NSAIDs.…”

“…5 The clinical correlate of the pivotal role of gastric acid in the development of gastroduodenal mucosal injury is that proton pump inhibitor (PPI) co-therapy has been shown to heal, maintain healing and reduce the risk of developing NSAIDrelated ulcers [6][7][8][9][10][11] and to decrease NSAID-related upper gastrointestinal (GI) symptoms. 8,9,12,13 Practice guidelines often recommend co-prescribing an acid inhibitor, such as a PPI, with NSAIDs in patients at risk of developing GI complications. [14][15][16] However, no studies have compared the pharmacodynamic actions of different PPIs in controlling intragastric acidity in patients using NSAIDs.…”

Long-term management of GERD in the elderly with pantoprazole

“…Pantoprazole has a higher chemical stability at neutral and moderately acidic pH compared with other PPIs, which makes it less likely to become activated in moderately acidic compartments of the body. Most importantly, it has a low potential for metabolic interactions with cytochrome P450-dependent oxidase system and so it is particularly suitable for patients in co-medications (Stupnicki et al 2004). …”