By Abdul Sattar Sohrani
An ibuprofen–famotidine combination, is associated with a reduced incidence of upper gastrointestinal events in patients taking long-term nonsteroidal anti-inflammatory drugs (NSAIDs), according to findings from a phase 3 study.
High-dose histamine2-receptor antagonists have been shown to protect against NSAID-induced gastrointestinal injury. HZT-501 is a single-tablet formulation containing 800 mg of ibuprofen and 26.6 mg of the histamine2-receptor antagonist famotidine. It is currently under review by the US Food and Drug Administration.
Two studies were presented here at the American College of Rheumatology 2010 Annual Meeting. Michael Weinblatt, MD, from Brigham and Women’s Hospital in Boston, Massachusetts, and colleagues presented the results of the Registration Endoscopic Study to Determine Ulcer Formation of HZT-501 Compared to Ibuprofen: Efficacy and Safety Study, also known as the REDUCE-1 and REDUCE-2 trials.
The 24-week, double-blind, randomized phase 3 trials compared HZT-501 with ibuprofen, administered 3 times daily.
Patients between 40 and 80 years of age who were expected to require daily NSAID therapy for at least 6 months, with no history of upper gastrointestinal ulcer complications, were randomly assigned, in a 2:1 ratio, to receive HZT-501 or ibuprofen 800 mg. Concomitant low-dose aspirin (?325 mg daily) and oral anticoagulants were permitted.
Of the 1533 patients, 1022 received HZT-501 and 511 received ibuprofen. Outcomes were evaluated at 8, 16, and 24 weeks.
HZT-501 reduced the incidence of upper gastrointestinal ulcers, relative to ibuprofen alone, for both the entire study population (14.0% vs 34.5%; P = .004) and the subgroup receiving low-dose aspirin (14.1% vs 26.5%; P < .0001).
In addition, the discontinuation rate was significantly lower in the HZT-501 group than in the ibuprofen group (31.0% vs 42.9%; P < .0001), primarily because of a reduced incidence of dyspepsia. The incidences of other treatment-induced adverse events were comparable between groups.
At the same meeting, Michael Schiff, MD, from the University of Colorado, in Denver, reported the results of a follow-up study of the REDUCE-1 and REDUCE-2 trials.
The researchers compared the outcome of continued HZT-501 with that of ibuprofen alone. Patients who completed 1 of the two 28-week trials with no ulcer development and who were expected to require continuing NSAID treatment were eligible for an additional 28 weeks of treatment on the same double-blind treatment assignment, with no crossover.
A total of 179 patients were enrolled in the follow-up study: 132 patients received HZT-501 (112 completed 28 weeks of treatment), and 47 patients received ibuprofen (38 completed treatment). The incidence of treatment-induced adverse events was comparable between the 2 groups for the 52-week period. There were no statistically significant differences in discontinuation rates or safety parameters, suggesting that HZT-501 is a safe alternative to ibuprofen alone.
“Ibuprofen is the most commonly used nonsteroidal drug by patients for many forms of arthritis, as well as pain syndromes, and compliance has been a big issue in the clinic,” Dr. Schiff told Medscape Medical News. He suggested that HZT-501 might improve compliance, and therefore decrease adverse events, such as gastrointestinal bleeding and hospitalizations.
Jeffrey Sherman, MD, a spokesperson for the manufacturer, Horizon Pharma, noted that the reduction in ulcer risk was evident in multiple populations, including older and younger patients, patients with a history of ulcer, and users of low-dose aspirin.
Independent commentator Jay L. Goldstein, MD, from the University of Illinois at Chicago, noted that these findings further confirm the efficacy of acid suppression in reducing endoscopic damage associated with NSAID use.
“The use of fixed-dose combinations, coupled with patient education, may lead to better adherence and improved long-term outcomes,” Dr. Goldstein told Medscape Medical News. “These findings need further confirmation, but endoscopic ulcers may be a surrogate marker for upper