Decreased Use of Cox-2 Inhibitors Is Increasing Gastrointestinal Complications

Newswise — An increasing number of elderly users of non-steroidal anti-inflammatory drugs may be at greater risk of serious gastrointestinal complications, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.

NSAIDs are a class of medications that work to decrease inflammation, pain and fever. Traditional NSAIDs include aspirin, ibuprofen (e.g., Advil, Motrin), naproxen (e.g., Aleve) and many other generic and brand name drugs. However, these drugs may harm the stomach, causing ulcers and complications, such as bleeding, perforation and obstruction.

These gastrointestinal complications from NSAIDs are reduced by the use of selective COX-2 inhibitors (currently, Celebrex is the only COX-2 inhibitor on the market), an NSAID that targets the COX-2 enzyme responsible for inflammation and pain, while reducing the risk of ulcers. Association of cardiovascular complications with the use of COX-2 inhibitors has led to the withdrawal of certain drugs from the market and a decline in the use of these drugs in patients with arthritis. Other drugs that reduce the risk of GI complications are the proton pump inhibitors (e.g., Prilosec, Nexium, Prevacid, Aciphex), which are a group of drugs that reduce acid production in the stomach, and misoprostol (Cytotec), which protects the stomach lining.

Researchers recently observed a significant increase in the rate of serious GI complications in relation to the decreasing prescription of selective COX-2 inhibitors and gastroprotective drugs.

Studying a group of patients " who were over the age of 65, diagnosed with arthritis, and treated with NSAIDS for at least 30 days " from 1997 to 2005, researchers included a total of 4,474,074 prescriptions for NSAIDS in the study and tracked the rate of serious ulcer complications (hospitalizations and/or emergency room visits for complicated gastric and duodenal ulcers) per 100,000 prescriptions.

The increasing implementation of good gastroprotection strategies reached a peak in 2004 when the percent of patients not receiving gastroprotection (Gastroprotection Gap) reached 14 percent from 79 percent in 1997. However, this gap more than doubled, reaching approximately 35 percent in 2005, following a decline in selective COX-2 inhibitor use, without a commensurate increase in other gastroprotective therapies. As the gastroprotection gap increased in 2005, a sharp rise in serious GI complications was observed.

"This trend, if left unchanged, will undoubtedly increase morbidity and mortality from NSAID-related ulcer complications to levels unacceptable for optimal medical care," said Gurkirpal Singh, MD; adjunct clinical professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine; chief science officer, Institute of Clinical Outcomes Research and Education; and an investigator in the study.

The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Editor's Notes: Dr. Singh will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 11:00 am " 12:30 pm ET on Thursday, November 8, 2007, in Hall C. Dr. Singh will be available for media questions and briefing at 1:30 pm ET on Saturday, November 10 in the on-site press conference room, Room 251.

Presentation Number: 668

A New Safety Warning: Decreased Gastroprotection is Associated with an Increase of Serious Ulcer Complications in Elderly Users of NSAIDs

Gurkirpal Singh1, Shweta Vadhavkar2, Alka Mithal2, George Triadafilopoulos1. 1Stanford University School of Medicine, Palo Alto, CA; 2Institute of Clinical Outcomes Research and Education (ICORE), Palo Alto, CA

Background: Gastrointestinal (GI) complications from NSAIDs are significantly reduced by the use of selective COX-2 inhibitors, concomitant proton pump inhibitors (PPIs) or misoprostol. Recent media attention on the potential association of cardiovascular events with selective COX-2 inhibitors and market withdrawals resulted in a large decline in the use of these drugs. In this study, we correlate the rate of serious GI complications to the changes in prescription patterns of gastroprotective agents.

Objectives: To study change in the rate of serious GI complications in a large cohort of elderly arthritis patients in the US from January 1, 1997 to June 30, 2005.

Methods: MediCal, the Medicaid program for California, is the largest Medicaid program in the US, with over 7 million participants per year. All study drugs were available without formulary restrictions or co-payments. We studied individuals with physician-diagnosed arthritis who were over 65 years of age and treated with NSAIDs for at least 30 days.

Results: A total of 4,474,074 prescriptions for NSAIDs were included in the study. Table shows the use of selective COX-2 inhibitors and concomitant PPIs or misoprostol, as a percentage of all NSAID use, and the rate of serious ulcer complications (hospitalizations and/or ER visits for complicated gastric and duodenal ulcers) per 100,000 prescriptions. The increasing implementation of gastroprotection strategies over the past several years reached a peak in 2004 when the percent of patients not receiving gastroprotection (Gastroprotection Gap) reached 14% from 79% in 1997. However, this gap more than doubled, reaching ~35% in 2005, following a decline in selective COX-2 inhibitor use, without a commensurate increase in other gastroprotective therapies. The rate of serious GI complications dropped from 682 per 100,000 prescriptions in 1997 to 357 in 2004 (p<0.0001). The sharpest decline was seen from 1999 to 2000 (579 to 423); this corresponded with a large decline in gastroprotection gap (55.6% to 25.2%). As the gastroprotection gap increased in 2005, a sharp rise in serious GI complications (from 357 to 434, 21%, p<0.0001) was observed.

Table: Year COX-2 inhibitors PPI MisoprostolGastroprotection gap Serious ulcer complications (per 100,000 NSAID prescriptions)1997 0.0% 11.3% 9.6% 79.1% 682.31998 0.0% 13.4% 9.9% 76.7% 635.71999 30.6% 8.7% 5.0% 55.6% 579.52000 69.0% 4.4% 1.5% 25.2% 423.22001 76.6% 4.0% 0.8% 18.7% 390.62002 77.6% 4.8% 0.6% 17.1% 409.12003 80.0% 5.1% 0.4% 14.5% 380.62004 79.1% 6.4% 0.5% 13.9% 357.22005 43.1% 20.5% 1.6% 34.8% 433.7

Conclusion: Recent safety concerns and market shifts have resulted in an increasing number of elderly users of NSAIDs again being left without appropriate gastroprotection, resulting in an increase in serious GI complications. This trend, if left unchanged, will undoubtedly increase morbidity and mortality from NSAID-related ulcer complications to levels unacceptable for optimal medical care.

Disclosure Block: G. Singh, Novartis, 2; Astra-Zeneca, 2; Pfizer, 2; Pfizer, 8; S. Vadhavkar, None; A. Mithal, None; G. Triadafilopoulos, Astra-Zeneca, 8; Pfizer, 8; TAP, 8.