Pain Management
NSAID Induced GI Side Effects: A Widespread Problem
It is well known that patients taking NSAIDs for prolonged periods are at increased risk for serious and nuisance GI side effects. NSAID induced GI complications represent one of the leading drug toxicities in the United States.
Over 100,000 hospitalizations occur each year in the U.S. for NSAID related GI complications. The mortality rate for these patients ranges between 5-10% with an estimated 16,500 related deaths in the U.S. each year. Annual direct costs associated with NSAID toxicities are estimated at over $2 billion.
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An estimated 16,500 related deaths and 100,000 hospitalizations occur each year in the U.S. from NSAID related GI complications |
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Number of Deaths by Cause
Source:
Wolfe, M. et. al Gastrointestinal Toxicity of Nonsteroidal Antiinflammatory Drugs, NEJM. 1999: 1888-1899. "National Adherence to Evidence Based Guidelines for Prescription of Non-Steroidal Anti-Inflammatory Drugs"
Low Compliance
Despite being one of the most prevalent and potentially life threatening drug related risks, GI protectants are often not co-prescribed to high risk NSAID patients. Estimates indicate that as low as 27% of high risk patients are currently treated with concomitant GI therapy.
In addition, studies have shown sub-optimal patient compliance when using preventative GI prophylaxis therapy (PPI's and H2 Antagonists) together with NSAID's. A recent study (Sturkenboom, et.al., Aliment Pharmacol Therapy 2003) followed 784 patients and concluded that as many as 37% were non-adherent during the first course of treatment. This number increased significantly to 61% over time (by the patient's third prescription).
The Added Burden of Dyspepsia (Upset Stomach) and "Minor" Side Effects
A large number of people also suffer from minor nuisance side effects while on NSAID therapy. In general, at least 10 to 20 percent of patients have dyspepsia while taking an NSAID, although the prevalence may range from 5 to 50 percent. Within a six-month period of treatment, 5 to 15 percent of patients with rheumatoid arthritis can be expected to discontinue NSAID therapy because of dyspepsia.
A Changing Global Market
Over 1.5 billion people worldwide suffer from chronic pain, including over 60 million who suffer from osteoarthritis. The global market for mild to severe pain medications - estimated at more than $10 billion in 2004 - is one of the mostly widely prescribed therapeutic classes of drugs.The Cox-2 selective inhibitors that were introduced in 1997 offered the promise of pain management with a reduction in GI complications commonly associated with traditional NSAIDs. By 2004, over 100 million prescriptions were written annually for both NSAIDs (ibuprofen, naproxen, diclofenac, etc.) and Cox-2 Inhibitors (Vioxx, Celebrex, Bextra) in the U.S. alone. Cox-2 Inhibitors quickly dominated worldwide sales at $6.5 billion compared to $2.5 billion for the traditional NSAID's.
The Product Void - Demise of Cox-2 Inhibitors
In September of 2004, Vioxx was removed from the U.S. market due to reports of cardiovascular-associated deaths, followed by the removal of Bextra in April 2005. This turn of events resulted in a 65% decline in worldwide sales of the Cox-2 inhibitors. In the U.S., total annual prescriptions for Cox-2 inhibitors dropped from 53 million to 18 million. During the same period, total annual U.S. prescriptions for traditional NSAIDs grew by over 20% - from 60 million to 73 million - as patients and physicians returned to the known efficacy of this category of pain medications.
TRx Total U.S. Prescriptions for NSAID and Cox-2 Inhibitor Classes
Source: IMS NPA, December 2005
REFERENCES:
IMS, National Prescription Audit, December 2005
Arrowhead Publishers: Pain Therapeutics 2005 Market Dynamics Outlook.
Recent Considerations in Non-Steroidal Anti-Inflammatory Gastropathy" Am J Med. 1998; 105 (1B): 31S- 38S.
"National Adherence to Evidence Based Guidelines for Prescription of Non-Steroidal Anti-Inflammatory Drugs" Gastroenterology. 2005; 129: 1171- 1178.
Sturkenboom et al. Aliment Pharmacol Ther. 2003 Dec; 18 (11-12): 1137-1147.
Chambers, C.V. A Cohort Study of NSAID Use and the Management of Related Gastrointestinal Symptoms by Primary Care Patients, P&T, 2003, 28(7): 462.