title: Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients.
abstract: 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.
authors.affiliation: General Hospital Graz-West, Department of Gastroenterology, Graz, Austria. thaddaeus.stupnicki@lkh-grazwest.at
authors.forename: T
authors.initials: T
authors.lastname: Stupnicki
authors.forename: K
authors.initials: K
authors.lastname: Dietrich
authors.forename: P
authors.initials: P
authors.lastname: González-Carro
authors.forename: A
authors.initials: A
authors.lastname: Straszak
authors.forename: A
authors.initials: A
authors.lastname: Terjung
authors.forename: K B
authors.initials: KB
authors.lastname: Thomas
authors.forename: R
authors.initials: R
authors.lastname: Lühmann
authors.forename: R
authors.initials: R
authors.lastname: Fischer
mesh_terms: 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
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D013454:Sulfoxides; D016595:Misoprostol; D000077402:Pantoprazole; D009853:Omeprazole