Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients.
OBJECTIVE
To compare the efficacy and tolerability of pantoprazole 20 mg once daily (o.d.) with misoprostol 200 microg 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 microg 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.


CONCLUSIONS
Pantoprazole 20 mg o.d. is superior to misoprostol 200 microg 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.
Stupnicki
T
T
General Hospital Graz-West, Department of Gastroenterology, Graz, Austria. thaddaeus.stupnicki@lkh-grazwest.at
Dietrich
K
K
González-Carro
P
P
Straszak
A
A
Terjung
A
A
Thomas
K B
KB
Lühmann
R
R
Fischer
R
R
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016595:Misoprostol / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D012216:Rheumatic Diseases / Q000188:drug therapy*; D012307:Risk Factors; D013454:Sulfoxides / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D013454:Sulfoxides; D016595:Misoprostol; D000077402:Pantoprazole; D009853:Omeprazole