One-year safety of ibuprofen/famotidine fixed combination versus ibuprofen alone: pooled analyses of two 24-week randomized, double-blind trials and a follow-on extension

Abstract

Objective:

To evaluate the safety of the fixed combination of ibuprofen and famotidine compared with ibuprofen alone from two 24-week, multicenter, double-blind trials designed to evaluate the comparative incidence of endoscopically documented upper gastrointestinal ulcers and a 28-week double-blind extension study.

Research design and methods:

Safety was analyzed by pooling data from the two double-blind trials and the follow-on study. Safety was assessed by monitoring the incidence, causality, and severity of adverse events (AEs).

Results:

In the pivotal efficacy and safety trials, discontinuation rates due to any cause and dyspepsia were significantly lower for the ibuprofen/famotidine combination versus ibuprofen alone. Other than dyspepsia, gastrointestinal and cardiovascular AEs of special interest were similar. Events judged to be treatment related were significantly lower with the ibuprofen/famotidine combination (20.6% vs. 25%). In the safety extension population, there were no differences in the discontinuation rates and the reporting of AEs or serious AEs (SAEs) between the two groups. Gastrointestinal-related events were similar between the groups. Incidence of cardiovascular-related AEs of special interest were 11% (ibuprofen/famotidine) and 2% (ibuprofen) (p = 0.06), possibly due to a higher number of rheumatoid arthritis patients in the combination group. Of these, 80% were reports of hypertension (8% ibuprofen/famotidine vs. 2% ibuprofen). Three cases of hypertension in the ibuprofen/famotidine group were considered treatment related. The probability of a cardiovascular event decreased during days 112–167 of treatment and remained low with continued treatment.

Conclusions:

One-year safety data from two pivotal trials and a long-term extension study indicate that the ibuprofen/famotidine combination demonstrates a favorable gastrointestinal safety profile and more patients continued on therapy compared to ibuprofen alone. No new safety signals have been identified. These data offer additional evidence supporting a new therapeutic option to improve gastrointestinal safety and adherence for patients who require long-term ibuprofen.

Keywords: :

• Arthritis, rheumatoid
• Cardiovascular
• Famotidine
• Gastrointestinal
• Ibuprofen
• Non-steroidal anti-inflammatory agents
• Safety

Transparency

Declaration of funding

The design, study conduct, and financial support for this study were provided by Horizon Pharma, Inc. Horizon participated in the interpretation of data, review, and approval of the manuscript.

Declaration of financial/other relationships

J.D.K., A.Y.G., and J.B. have disclosed that they are employees of Horizon Pharma, Inc. A.E.B. and R.J.H. have disclosed that they have been consultants for Horizon Pharma, Inc. A.E.B. has also been a speaker for AbbVie, Questcor, and UCB.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Tonya Goodman and Cathryn M. Carter MS of Arbor Communications Inc., Ann Arbor, MI, USA for medical writing support; this support was funded by Horizon Pharma Inc.

Previous presentations: Goldstein JL, Lakhanpal S, Cohen SB, et al. Long term safety of an NSAID with built-in gastroprotection for treatment of pain and inflammation related to OA and RA: comparative results from blinded and open label one year safety trials of a single-tablet combination of ibuprofen-famotidine [abstract no. Mo1215]. Gastroenterology 2011;140(5 Suppl 1):S585; and Weinblatt ME, Genovese MC, Kivitz AJ, et al. 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 [abstract no. 945]. Arthritis Rheum 2010;62(10 Suppl):S391-2.