Researchers at the University of California School of Medicine, San Francisco, have examined the association between long-term use of nonsteroidal antiinflammatory drugs ( NSAIDs ) and non-Hodgkin lymphoma ( NHL ), using data collected between October 2001 and May 2004 in an ongoing population-based case-control study in the San Francisco Bay Area.

Non-Hodgkin lymphoma cases were identified using rapid case ascertainment and Surveillance, Epidemiology, and End Results registry data.

Control participants were frequency-matched to cases by age, sex, and county of residence.

Participants completed in-person interviews designed to measure potential NHL risk factors. Questions were asked regarding use during the past 20 years of Aspirin, prescription and over-the-counter nonselective NSAIDs, and cyclooxygenase-2 ( COX-2 ) inhibitors.

A total of 1,000 cases and 1,060 controls contributed data for interim analyses.

After adjustment for age and sex, there was no consistent association between long-term use and non-Hodgkin lymphoma for all NSAIDs combined, Aspirin, nonselective NSAIDs, and COX-2 inhibitors.

For women, long-term Aspirin use may be associated with a decreased risk of NHL ( for 3 – < 9 years of use, odds ratio = 0.41 ).

Conversely, although the confidence intervals were wide, the adjusted odds ratios for COX-2 inhibitor use were nearly twofold for women, indicating a possible increase in NHL risk associated with regular use of COX-2 inhibitors.


COX-2 inhibitors

COX-2 inhibitors are a class of drugs which selectively inhibit cyclooxygenase-2 ( COX-2 ) enzyme.
NSAIDs ( non-steroidal anti-inflammatory drugs ) that inhibit only COX-2 enzymes were created to allow people to have relief from pain and inflammation while reducing the chances of stomach bleeding, that can occur when NSAIDs are taken regularly for long periods of time.

COX-2 inhibitors include Celecoxib ( Celebrex ), Etoricoxib ( Arcoxia ), Lumiracoxib ( Prexige ), Rofecoxib ( Vioxx ), Valdecoxib ( Bextra ).

Merck & Co.announced a voluntary withdrawal of Vioxx from the U.S. and worldwide market in September 2004 due to safety concerns of an increased risk of cardiovascular events ( including myocardial infarction and stroke ) in patients on Vioxx.
Vioxx was a COX-2 selective, non-steroidal anti-inflammatory drug ( NSAID ) that was approved by FDA in May 1999 for the relief of the signs and symptoms of osteoarthritis, for the management of acute pain in adults, and for the treatment of menstrual symptoms. Vioxx was later approved for the relief of the signs and symptoms of rheumatoid arthritis in adults and children.

The FDA announced actions regarding the marketing of NSAIDs ( non-steroidal anti-inflammatory drugs ) in April 2005.
The actions include changes for COX-2 inhibitors, as well as prescription and non-prescription ( over-the-counter ) NSAIDs.
The FDA asked Pfizer to voluntarily remove Bextra from the market because " the overall risk versus benefit profile for the drug is unfavorable."
The FDA asked Pfizer to include a boxed warning in the Celebrex label ( package insert ) stating an increased risk of cardiovascular events and potentially life-threatening gastrointestinal bleeding associated with its use.

Source:

1) American Journal of Epidemiology, 2006

2) FDA, 2006


XagenaMedicine2006