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News last week about celecoxib shows how challenging it can be to understand the risks and benefits of newly developed drugs. This is particularly true when the findings of one study contradict those of past studies. And that’s exactly what has happened with celecoxib.
Anti-inflammatory medications: pros and cons
The FDA approved celecoxib (Celebrex) in 1999. This anti-inflammatory medication can be a highly effective treatment for arthritis and other painful conditions. It was developed with the hope that it would be at least as effective as other anti-inflammatory medications (such as ibuprofen or naproxen) but cause less stomach irritation. Developing a safer anti-inflammatory medication is a worthy goal, since stomach irritation can not only cause annoying pain or nausea, but it can also lead to ulcers, bleeding, or perforation. These medications can also increase blood pressure and cause kidney problems.
Celecoxib is known as a COX-2 inhibitor — that’s because it targets an enzyme (COX-2) involved in inflammation. Ibuprofen and naproxen (and many other anti-inflammatories) target COX-1 and COX-2. They’re called “non-selective” anti-inflammatory drugs. Because of where these enzymes are found in the body, the COX-2 selective medications seemed capable of dampening down inflammation while going easier on the stomach.
And that was true. Celecoxib — and other COX-2 inhibitors, such as rofecoxib (Vioxx) — did cause less stomach trouble. But soon after its approval, studies suggested other concerns: an increased risk of heart attack and stroke. Rofecoxib was removed from the market in 2004. And while the FDA allowed celecoxib to remain on the market, it required the manufacturer to issue additional warnings to patients. It also required additional study. And that’s why celecoxib is back in the news this week. The results of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen) trial were released. And the news is good for celecoxib.
Results suggests lower cardiovascular disease risk — and fewer side effects — than expected
The PRECISION trial is a carefully designed and powerful study that analyzed the impact of celecoxib on cardiovascular disease. The study spanned 926 medical centers in 13 countries and enrolled more than 24,000 patients with two of the most common types of arthritis (osteoarthritis and rheumatoid arthritis). Each study subject had a higher than average risk for cardiovascular disease due to a history of high blood pressure or high cholesterol.
Study subjects were divided into three groups who took anti-inflammatory medications every day: one group took celecoxib, one group took ibuprofen, and the last group took naproxen.
Study subjects taking celecoxib in moderate doses were
- no more likely than those taking ibuprofen or naproxen to have a fatal or non-fatal heart attack or stroke
- less likely than those taking ibuprofen or naproxen to have significant gastrointestinal problems, such as serious bleeding
- less likely than those taking ibuprofen to have kidney problems or hospital admission for high blood pressure.
What does this mean for you?
It’s rare that a single study provides a definitive answer or changes practice overnight. But this was a large, well-designed, and expensive study that is unlikely to be repeated any time soon. And, another study of lower-risk people came to a similar conclusion just last year.
Still, questions may yet come up regarding:
- The lack of a placebo group. As suggested by some prior research, it is possible that all three of the drugs used in this study increase the risk of cardiovascular problems; without a control group, it’s impossible to say.
- Dosing. Study subjects were allowed to take up to 400 mg/day of celecoxib if they had rheumatoid arthritis but only 200 mg/day if they had osteoarthritis. In real life doctors may prescribe a wider range of doses.
- Reason for treatment. This study only included people with rheumatoid arthritis or osteoarthritis. The results might be different if people with other conditions had been included.
- Other medical problems. The risks and benefits of celecoxib in people with other medical problems (such as significant kidney disease) are uncertain because this study excluded them.
- Other medical treatments. All patients in this study took a medication to protect the stomach; outside of studies, that’s not always the case.
While these issues are valid, I think this study does provide a significant measure of reassurance regarding the cardiovascular risks of celecoxib. And it may encourage doctors who thought the drug was too risky to prescribe it more often.
This new research shows in a dramatic way why “more research is needed” is not just a tagline at the end of so many medical news stories. And in the case of celecoxib, the result of the additional research is good news indeed.