Arthritis therapy tied to liver injury cases

NEW YORK (Reuters Health) - A "medical food" sold as an arthritis treatment may have caused four cases of temporary liver damage, researchers reported Monday.

The product in question is called flavocoxid, sold under the brand-name Limbrel. It's a mix of plant compounds called flavonoids, including catechins -- substances best known as components of green tea.

Limbrel is considered a medical food, which makes it different from a dietary supplement. It is available by prescription only, to treat osteoarthritis -- the common, "wear-and-tear" form of arthritis caused by cartilage breakdown in the joints.

But medical foods are different from prescription drugs in that they don't have to be proven safe and effective before hitting the market.

In the new report, published in the Annals of Internal Medicine, researchers describe four cases in which Limbrel users developed temporary liver "injury."

That meant symptoms like abdominal pain, jaundice (yellowing of the skin), intensely itchy skin and fever.

All of the patients recovered after they stopped using the product.

The researchers cannot say with certainty that all four cases were caused by Limbrel.

"There's no single test you can do to say, ?Bingo, it's caused by this,'" said lead researcher Dr. Naga Chalasani, of Indiana University School of Medicine in Indianapolis.

But he said that three of the cases were "highly likely" to have been caused by Limbrel. The fourth was "possibly" caused by the product.

Timing was a big clue. All four patients developed signs of liver toxicity within three months of starting the arthritis treatment. And all got better within three to 12 weeks of stopping it.

That relatively quick recovery is the good news, Chalasani said. "It seems like you stop taking it, and the liver injury improves pretty quickly, in a matter of weeks."

Scottsdale, Arizona-based Primus Pharmaceuticals, which makes Limbrel, did not return calls seeking a comment.

The four liver-damage cases turned up as part of an ongoing surveillance study of liver injury caused by drugs or herbal supplements. Between 2004 and 2010, researchers at several U.S. medical centers enrolled 877 patients who were thought to have liver damage from a medication or supplement.

Four of those cases were linked to Limbrel.

It's not fully clear why the product would damage the liver.

"That's the million-dollar question," Chalasani said.

But he and his colleagues suspect it may be the catechin content. Green tea extracts, which contain high concentrations of catechins, have been linked to liver toxicity.

Even if catechins are to blame, that still leaves the question of why only certain Limbrel users would develop liver problems. "There has to also be some kind of susceptibility" to liver injury, Chalasani said, noting that it could be a genetic vulnerability.

Also unclear is how many Limbrel users out there may have suffered liver injury.

Besides the four cases in this report, Primus has gotten eight reports of "clinically apparent" liver toxicity that the company shared with Chalasani's team.

The product is not widely used. Worldwide, it seems that about 400,000 prescriptions have been written for Limbrel, Chalasani noted.

He suggested that if you are one of those users, you should pay attention to any potential signs of liver toxicity, like abdominal pain and jaundice. "If you develop symptoms, stop using it and talk to your doctor," Chalasani said.

But an editorial published with the study says that people should be discouraged from using Limbrel -- and other dietary supplements marketed for arthritis.

Other anti-arthritis supplements include chondroitin and glucosamine, and there is little evidence they work, write Drs. Stephan Reichenbach and Peter Juni of the University of Bern, in Switzerland.

In the U.S., supplements and medical foods are not subject to the same regulation as drugs. That is, manufacturers can market them without showing proof to the Food and Drug Administration that the products work.

"Given the widespread use and potential harm of medical food and food supplements, the policy of marketing these products in the absence of clinical evidence may need to be reconsidered," Reichenbach and Juni write.

Unfortunately for arthritis sufferers, few treatments that are both safe and effective exist, the researchers point out.

Simple steps, like exercise and an occasional dose of acetaminophen, might help people with mild arthritis. But once the pain gets more severe, options are limited.

Some people find relief by regularly taking painkillers called non-steroidal anti-inflammatory drugs (NSAIDs) -- which include naproxen, ibuprofen and the prescription drug celecoxib (Celebrex).

But those drugs can cause stomach irritation and ulcers, and studies have linked them to an increased risk of heart attack.

Anti-inflammatory cortisone shots can help some people temporarily, but they are not a long-term fix. And the effectiveness of another option -- injections of joint-lubricating hyaluronic acid -- has been seriously questioned.

Chalasani said that people should choose their arthritis treatment after a careful discussion with their doctor. When it comes to dietary supplements, he said, don't assume they are completely safe simply because they are described as "natural."

SOURCE: http://bit.ly/N0G6LY Annals of Internal Medicine, June 19, 2012.

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