Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Long Term Safety of an NSAID with Built-in Gastroprotection for Treatment of Pain and Inflammation Related to OA and RA: Results from a One Year Safety Trial of a Single-Tablet Combination of Ibuprofen-Famotidine vs. Ibuprofen Alone.

Schiff6,  Michael H., Genovese5,  Mark C., Kivitz1,  Alan J., Bello4,  Alfonso E., Sherman3,  Jeffrey W., Grahn3,  Amy, Weinblatt2,  Michael E.

Altoona Arthritis & Osteo Ctr, Duncansville, PA
Brigham & Womens Hospital, Boston, MA
Horizon Pharma, Inc., Northbrook, IL
Illinois Bone & Joint Inst, Glenview, IL
Stanford University, Stanford, Sunnyvale, CA
University of Colorado, Denver, Greenwood Village, CO

Background:

Gastrointestinal (GI) toxicity remains a major concern with NSAIDs used in the treatment of OA, RA, and pain. Proton pump inhibitors (PPI) and other gastroprotective agents are recommended to decrease NSAID-associated GI injury. Concerns exist regarding the potential for PPIs to adversely interact with antiplatelet agents as well as increase the risk of fractures. High-dose H2 receptor antagonists provide significant benefit in decreasing NSAID-associated GI injury (Cochrane review). Most NSAID users at increased risk for GI events do not receive or adhere to gastroprotective co-therapy. HZT-501 [single-tablet combination of ibuprofen (IBU; 800 mg) and famotidine (FAM; 26.6 mg)] has been shown to significantly reduce upper GI ulcers as compared to IBU (800 mg) alone given thrice daily (REDUCE-1 and REDUCE-2).

Methods:

Assessment of long term safety of HZT-501 or IBU tablets for up to 52 wks of treatment for patients with OA, RA or moderate pain. Patients who completed one of two large 24-week double-blind prospective trials of identical design (REDUCE-1 or REDUCE-2) were eligible for an additional 28 weeks of treatment; enrollment goal was at least 150 patients. Patients 40–80 yrs expected to require daily NSAID therapy >= 6 months with no history of ulcer complications, a negative H. pylori stool antigen test and baseline EGD showing no ulcers and <5 erosions in the upper GI tract were randomly assigned in a 2:1 ratio either to HZT-501 or IBU tablets. Randomization was stratified based on concomitant low-dose aspirin/anticoagulant therapy and prior ulcer history. Patients completing 24 weeks of blinded treatment (no ulcer development; expected to continue requiring daily NSAID therapy) were eligible to enroll into a follow-on study for an additional 28 weeks on the same double-blind treatment assignment. Crossover between treatments was not allowed. Safety data included serious adverse events (SAEs), treatment emergent adverse events (TEAEs), clinical laboratory assessments, vital signs, and physical exams.

Results:

A total of 179 subjects were enrolled into the follow-on study, 132 received HZT-501 (112 completed) and 47 received ibuprofen (38 completed). The incidence of TEAEs was comparable in both groups for the overall 52-week period. The Table shows the differences for HZT-501 vs. IBU for discontinuation, serious adverse events (SAE) and TEAEs of interest over 52 wks. There were no clinically relevant differences between treatment groups in vital signs, hematology, biochemistry values or physical exams.

Table.

 REDUCE 1 & 2 Follow-on Population
 HZT-501 (N = 132)IBU (N = 47)p-value
Discontinuation15.2%19.1%0.505
SAEs6.1%6.4% 
TEAEs68.2%68.1%0.988
  Infections and Infestations34.8%36.2%0.878
  GI Disorders26.5%23.4%0.703
  Dyspepsia13.8%8.5%0.184
Cardiac Disorders0.8%0 
1Preferred term for patient reported adverse event

Conclusion:

These results show the safety of long-term use of HZT-501, together with the significant decrease in upper GI ulcers, demonstrate that HZT-501 offers a potential new option for OA, RA and pain patients.

To cite this abstract, please use the following information:
Schiff, Michael H., Genovese, Mark C., Kivitz, Alan J., Bello, Alfonso E., Sherman, Jeffrey W., Grahn, Amy, et al; Long Term Safety of an NSAID with Built-in Gastroprotection for Treatment of Pain and Inflammation Related to OA and RA: Results from a One Year Safety Trial of a Single-Tablet Combination of Ibuprofen-Famotidine vs. Ibuprofen Alone. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :946
DOI: 10.1002/art.28714

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