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Celecoxib scores ok on cardiac safety: a three-drug, 10-year trial found it equivalent, or "noninferior," to ibuprofen and naproxen.

Osteoarthritis (OA) and rheumatoid arthritis (RA) affect the lives of millions of people worldwide. OA is known for progressive damage to joint cartilage, which causes changes in the surrounding tissues. RA is a chronic disease that causes pain, stiffness, swelling, and limits range of motion and function of many joints; with RA, inflammation also can develop in other organs.

In the 1960s, nonsteroidal anti-inflammatory drugs (NSAIDs) were introduced and quickly became the most widely prescribed class of drugs in the world. NSAIDs inhibit inflammation accompanying OA and RA, but also can cause gastrointestinal upset.

The Role of Cyclooxygenase (COX). The body's inflammatory response involves an enzyme, cyclooxygenase (COX), that helps form prostanoids, key components in the development of inflammation. COX is a target for inflammation-inhibiting drugs. In the 1990s, researchers discovered that two types of COX enzymes existed, COX-1 and COX-2. Non-selective NSAIDs inhibit both COX-1 and COX-2.

But, in inhibiting all forms of COX, unwanted side effects result. COX-1 is present in most tissues and helps maintain the normal lining of the stomach as well as kidney and platelet function. COX-2 is present at inflammation sites. Thus, inhibiting COX-2 is a goal (less inflammation = less pain), but inhibiting COX-1 can lead to gastrointestinal problems, ulcers, kidney problems, and prolonged bleeding time.

Enter COX-2. In the late 1990s, the first COX-2 selective NSAID was introduced, to inhibit inflammation-promoting COX-2. While two others in its class of drugs, Vioxx and Bextra, were removed from the market in 2004 and 2005, respectively, celecoxib (Celebrex) remains available, but with a black box warning that it carries the risk of heart attack and stroke.

PRECISION Study. Researchers from Cleveland Clinic and Brigham and Women's Hospital, Boston, embarked on a 10-year trial (Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen, or PRECISION), involving 24,081 patients in 13 countries to investigate the relative cardiovascular safety of celecoxib compared to ibuprofen and naproxen. Ninety percent of patients enrolled suffered from OA; the other 10 percent, from RA. Patient results were as follows:

Primary outcome (cardiovascular death, nonfatal heart attack, nonfatal stroke) was 2.3 percent in the celecoxib group compared to 2.5 percent in the naproxen group, and 2.7 percent in the ibuprofen group, showing celecoxib to be "noninferior" to naproxen and ibuprofen. Celecoxib also was associated with a lower risk of gastrointestinal side effects than naproxen and ibuprofen, and lower risk of kidney events than ibuprofen, but not naproxen.

Other Outcomes. The rate of hospitalization and renal events was significantly lower in the celecoxib group than in the ibuprofen group, but not lower than in the naproxen group. In addition, there were significantly fewer gastrointestinal events and iron-deficiency anemia of gastrointestinal origin in the celecoxib group.

Drug doses comprised 100-200 mg of celecoxib twice a day, 600-800 mg of ibuprofen three times a day, or 375-500 mg of naproxen twice a day.

The research team concluded that in moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with respect to cardiovascular safety.


What Does "Noninferior" Mean?

"Non-inferiority" trials are devised to question whether a new treatment or medical intervention is comparable to the traditional standard therapy. Such a trial tries to establish that the new treatment is no worse than current standard care. This type of trial is devised when the new treatment provides advantages that would make it more preferable than the old treatment. For example, is it cheaper, safer, or less invasive than the standard treatment?

--Adapted from
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Title Annotation:BONES & JOINTS
Publication:Duke Medicine Health News
Date:Mar 1, 2017
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