I just sat on a panel for the FDA to discuss a study that compared the safety profiles of 3 NSAIDs: Celebrex (celecoxib), Aleve (naproxen) and Advil (ibuprofen). All NSAIDs (except aspirin) are proven to increase the risk of cardiovascular (CV) events (heart attack, stroke, myocardial infarction, etc.) which is why they must be used sparingly and carefully by anyone with increased heart or stroke risk. The study was designed to prove that celecoxib didn’t kill or harm more people than naproxen and ibuprofen.
After reading hundreds of pages of studies and listening to a full day of presentations and community input, I learned something: If I ever have arthritis pain or any chronic pain, I will NOT be using celecoxib, naproxen or ibuprofen.
The medical community is concerned that celecoxib might substantially increase the risk of CV events — even more than naproxen and ibuprofen. Celecoxib is also known as a COX-2 inhibitor, just like Vioxx (rofecoxib) and Bextra (valdecoxib), both infamously withdrawn from the market after reports surfaced of people having serious — and sometimes deadly — CV events after taking the medications.
The PRECISION Trial that we discussed at the FDA meeting was designed to determine if Celebrex was “non-inferior” to naproxen and ibuprofen. The study was flawed and only tested celecoxib at comparatively low levels. Vioxx and Bextra were more dangerous as the dose increased.
At low levels (100 mgs 2 times per day), Celebrex actually looked safer than naproxen and ibuprofen. My question: Would doctors have the restraint to not increase the FDA-recommended dose in the face of those patients who continue to have pain? Celebrex’s prescribing information states: “For management of acute pain and treatment of primary dysmenorrhea, the dosage is 400 mg initially, followed by an additional 200 mg dose if needed on the first day. On subsequent days, the recommended dose is 200 mg twice daily as needed.”
And many of those patients will have continued or breakthrough pain while using any of the 3 NSAIDs because they only work in about 30% of people and lower the pain amount by just 30%, according to a meta analysis (study of studies) conducted by Harvard University on OA knee pain. Ultram (tramadol) and stronger opioids were found to be just as ineffective, with about a 30% drop in pain.
During the PRECISION trial of people with RA and OA pain, about 70% of the people dropped out, which is in alignment with the low level of effectiveness. In the study, 24% of trial participants said the reason they dropped out was because the “adverse events” (side effects) were so severe that they couldn’t continue. Changes in diet and exercise have been proven to be very effective in managing the disease — and without the side effects of COX-2s and NSAIDs.
My recommendation to the FDA was that all 3 — celecoxib, naproxen and ibuprofen — should have a warning on the package that they should not be used for long-term or chronic pain because they are ineffective, have too many side effects and increase the risk for CV.