title: 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?
abstract: BACKGROUND
  Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with significant upper and lower gastrointestinal (GI) morbidity.
  
  
  OBJECTIVE
  To determine the efficacy and safety of pantoprazole versus placebo in controlling GI symptoms during treatment with NSAIDs and to evaluate the influence of potential response modifiers.
  
  
  METHODS
  800 patients with GI complaints during NSAID treatment were randomized to pantoprazole 20 mg once daily or placebo for 4 weeks in this double-blind, multicenter trial. Assessments included the difference in cumulated overall symptom load of any GI complaint during treatment (primary endpoint), proportion of days without GI symptoms, and influence of risk factors such as gender, age, alcohol consumption, smoking, Helicobacter pylori status, and GNB3 genotype SNP rs5443 (825C>T) on symptom load.
  
  
  RESULTS
  At 4 weeks, cumulated overall symptom load was significantly lower in pantoprazole than placebo recipients [p < 0.0001; intent-to-treat (ITT)]; the effect was statistically significant after 7 days' treatment. Pantoprazole versus placebo recipients had 54 versus 29% of days without GI symptoms (p < 0.0001; ITT). Neither common risk factors nor GNB3 genotype were significantly associated with therapeutic response, while GNB3 825TT versus CT was associated with a significantly higher baseline symptom load (p < 0.05).
  
  
  CONCLUSIONS
  In the population studied, treatment with the proton pump inhibitor pantoprazole significantly improves GI symptoms during NSAID therapy, irrespective of the risk factors investigated or GNB3 genotype.
authors: Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, University of Queensland, Woolloongabba, Qld., Australia. Gerald_Holtmann@health.qld.gov.au
authors: G
authors: G
authors: Holtmann
authors: C
authors: C
authors: van Rensburg
authors: T
authors: T
authors: Schwan
authors: P
authors: P
authors: Sander
authors: W
authors: W
authors: Siffert
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000428:Alcohol Drinking; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000188:drug therapy*; D005838:Genotype; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D012737:Sex Factors; D012907:Smoking
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; C454420:G-protein beta3 subunit; D054328:Proton Pump Inhibitors; D000077402:Pantoprazole; D020962:Heterotrimeric GTP-Binding Proteins