By Melissa Healy Los Angeles Times
WASHINGTON — Flavocoxid — an arthritis treatment marketed as an effective counter to joint inflammation — appears to cause “clinically significant liver injury” in some patients, and physicians should probably discourage their patients from taking it, says a new study and its accompanying editorial.
Drawing on the records of 877 patients followed by the national Drug-Induced Liver Injury Network, researchers publishing in the Annals of Internal Medicine cite three cases in which flavocoxid use was found to be the “very likely” cause of acute liver injury, and a fourth in which liver injury was found to be “possibly due to” flavocoxid use.
All four patients recovered their full liver function after discontinuing use of flavocoxid.
What could go wrong with a product that promises to tamp down inflammation with ingredients found in such foods as soy, cauliflower, kale, peanuts, apples, cocoa and green tea? At the same time, flavocoxid sounds like a regulated pharmaceutical product – it’s even got a “marketing name” – Limbrel – that sounds a lot like a drug that is widely prescribed for rheumatoid arthritis. Flavocoxid is even listed on several reputable prescription-drug sites.
So of course this “medical food product” has won the FDA’s blessing for safety and effectiveness, right? And it’s subject to the usual safety monitoring once it is approved for marketing to a wide population of patients, right?
Wrong on both counts.
Flavocoxid is “an interesting therapeutic alternative to non-steroidal anti-inflammatory drugs,” write Drs. Stephan Reichenbach and Peter Juni of the University of Bern in Switzerland, in an editorial that accompanies the Annals study. Laboratory studies suggest that flavocoxid’s plant-based bioflavenoids inhibit two enzymes implicated in the inflammatory process, and that it may act on arthritis pain and stiffness in much the same way that medications such as ibuprofen, naproxen and celecoxib do.
And an alternative to those medications would be welcome, especially if it did not carry some of the risks that come with those non-steroidal anti-inflammatory drugs: besides risking gastrointestinal side effects, patients who take such NSAIDs regularly have a two- to four-times higher risk of having or dying from a heart attack or stroke, Juni found in a recent study.
But because flavocoxid is classified as a nutritional supplement, no clinical trials demonstrating its safety and effectiveness in treating arthritis are required before it is sold: unless or until the FDA has mustered strong evidence suggesting otherwise, the product is considered safe for U.S. consumers.
Flavocoxid has been marketed to arthritis patients and their physicians since 2004. In 2009 and 2010, two clinical trials of flavocoxid become available to the public. While both favorably compared flavocoxid’s effectiveness to that of prescription naproxen, Reichenbach and Juni write that “neither trial satisfies current standards of reporting.”
The authors speculated that hypersensitivity to flavocoxid’s natural ingredients may have played a role in some of the patients’ reactions to the product. But they also noted that “unpredictable or unregulated concentrations of . polyphenolic substances” may “set the stage for toxicity.”
All of the authors of the Annals of Internal Medicine study are members of the Drug-Induced Liver Injury Network, a consortium of researchers that has been tracking patients with suspected drug-induced liver injury since 2004.