title: Risk of upper gastrointestinal ulcers in patients with osteoarthritis receiving single-tablet ibuprofen/famotidine versus ibuprofen alone: pooled efficacy and safety analyses of two randomized, double-blind, comparison trials.
abstract: BACKGROUND
  Although anti-inflammatory doses of ibuprofen are very effective in treating the signs and symptoms of osteoarthritis (OA), they come with an increased risk for gastrointestinal damage which can limit their use and decrease patient adherence to therapy.
  
  
  OBJECTIVE
  Assess the efficacy and safety of an ibuprofen/famotidine fixed-dose tablet for reducing the risk of upper gastrointestinal (UGI) ulcers compared with ibuprofen alone in OA patients.
  
  
  METHODS
  Osteoarthritis patients from previously completed randomized, double-blind, comparison registration trials (REDUCE-1 and 2) which included a broad pain patient population, were pooled and analyzed for (1) the risk of endoscopically identified UGI ulcers over 24 weeks and (2) comparative pre-specified treatment emergent adverse events (TEAEs). The primary outcomes were the comparative incidence of UGI, gastric, and duodenal ulcers and TEAEs in (1) the total OA population, (2) those aged ≥ 60 years, and (3) those on low dose aspirin. A total of 776 patients were randomized (safety population), and 713 were evaluable as the study population.
  
  
  RESULTS
  Upper gastrointestinal ulcer risk was statistically significantly reduced with the fixed dose tablet compared with ibuprofen alone by 44% in the overall population, 55% in those aged ≥ 60 years and 65% in those on low dose aspirin. Individually, gastric and duodenal ulcers were also significantly reduced in all groups analyzed. Adverse events of special interest were generally similar between the 2 groups, with the exception of dyspepsia. Relative risk reduction for dyspepsia in the overall population was 40% and 55% in those aged ≥ 60 years. Patients not receiving low dose aspirin had a 49% relative risk reduction in dyspepsia.
  
  
  CONCLUSIONS
  The fixed combination of ibuprofen/famotidine significantly reduced the risk for endoscopically documented gastrointestinal ulcers in OA patients and produced clinically meaningful reductions in patient reported dyspepsia compared with the ibuprofen alone.
authors.affiliation: Clinical Associate Professor of Medicine, University of Illinois- Chicago, College of Medicine, and Director of Rheumatology Research, Illinois Bone and Joint Institute, LLC, Glenview, IL.
authors.forename: Alfonso E
authors.initials: AE
authors.lastname: Bello
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Kent
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Grahn
authors.forename: Patricia
authors.initials: P
authors.lastname: Rice
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Holt
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D004338:Drug Combinations; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D015738:Famotidine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D013276:Stomach Ulcer / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D013607:Tablets
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D013607:Tablets; D015738:Famotidine; D007052:Ibuprofen