Ibuprofen/Famotidine versus Ibuprofen Alone in Chronic NSAID Users

Atlanta—A combination tablet of ibuprofen plus high-dose famotidine (a gastroprotectant) dubbed HZT-501 reduces gastrointestinal (GI) ulcers overall in chronic nonsteroidal antiinflammatory drug (NSAID) users as well as in a subset of NSAID users also taking low-dose aspirin, compared with ibuprofen alone, according to pooled results of 2, 24-week, doubleblind, controlled trials reported at the ACR meeting.

The findings were reported in a poster titled Efficacy, Safety, and Tolerability of HZT-501, Including Users of Low-Dose Aspirin, a Single-Tablet Combination of Ibuprofen-Famotidine: Results of Two Phase 3 Trials. The combination of prescription-strength ibuprofen and high-dose famotidine (unavailable in a single pill) in 1 tablet reduced ulcers by 50%, said the authors. M.E. Weinblatt, MD, Harvard Medical School, Boston, Massachusetts, was lead author of this study. The study was sponsored by Horizon Pharma USA, Inc, Northbrook, Illinois. Gastroprotection is important in chronic NSAID users, especially in those who also take low-dose aspirin. Famotidine 40 mg/day has been shown to provide gastroprotection in low-dose aspirin users similar to that provided by double doses of H2 receptor antagonists [Taha et al. Lancet. 2009].

HZT-501 is investigational and is under review by the Prescription Drug User Fee Act. REDUCE-1 and REDUCE-2 (Registration Endoscopic Study to Determine Ulcer Formation of HZT-501 Compared to Ibuprofen: Efficacy and Safety study) randomized 1533 patients taking NSAIDs for pain due to osteoarthritis, rheumatoid arthritis, chronic low back pain, chronic regional pan syndrome, and/or chronic soft tissue pain to receive either HZT-501 (n=1022) or ibuprofen (n=511) for 24 weeks. Low-dose aspirin users numbered 121 in the HZT-501 group and 79 in the ibuprofen group. To be included in the study, participants were required to take daily NSAIDs for >6 months and have no history of ulcer complications, be Helicobacter pylori negative, and endoscopynegative for ulcers at baseline, but could have <5 erosions in the gastrointestinal tract. Patients were evaluated at weeks 8, 16, and 24 with repeat endoscopy, physical exam, assessment for adverse events, and concomitant medications. Lab tests and tablet counts were also evaluated at these time points.

The populations of both REDUCE-1 and REDUCE-2 were well balanced for demographic characteristics. Mean age was 55 years, approximately 18% were ≥65 years of age, approximately two thirds were female, and approximately 6% had a prior ulcer. REDUCE-1 had a slightly higher percentage of low-dose aspirin and antithrombotic/anticoagulant users, as well as GI erosions. In a pooled analysis of results, HZT-501 was significantly superior to ibuprofen: the percentage of patients with upper GI ulcers according to cumulative crude proportion at week 24 overall was 11% for HZT-501 versus 21.9% for ibuprofen alone (P<.0001). Similar gastroprotection according to cumulative crude proportion at week 24 was observed in the subset of low-dose aspirin users: upper GI ulcers were reported in 12.8% versus 32.8%, respectively (P=.002). A forest plot for the relative risks of upper GI ulcers in the 2 treatment groups favored the combination tablet over ibuprofen for all subgroups, including age <65 or >65, prior ulcer or no prior ulcer, low-dose aspirin or no low-dose aspirin, and sex. The percentage of patients with treatmentemergent adverse events significantly favored the combination tablet: 31% versus 42.9%, respectively (P<.0001). Lower incidence of discontinuations and dyspepsia was observed with HZT-501 versus ibuprofen: dyspepsia was reported in 4.7% of the HZT-501 group versus 8% of the ibuprofen group (P=.009).