Panel looks at safety of arthritis drugs

By Rhonda Rowland
CNN Medical Unit

The safety of two drugs used to treat arthritis will be discussed by the Food and Drug Administration's Arthritis Advisory Committee Friday.

It's been three years since the treatment of rheumatoid arthritis was revolutionized with the introduction of Enbrel, a biologic drug that inhibits tumor necrosis factor (TNF), which plays a key role in promoting the disease process. A year later, a second TNF inhibitor called Remicade was introduced.

"These have been a major advance in rheumatology," said Dr. John Klippel, medical director of the Arthritis Foundation, "probably the single major advance in at least 50 years. The only thing comparable was the introduction of corticosteroids in the 1950's."

The committee will discuss ongoing safety concerns with TNF inhibitors to ensure product labels reflect what's been seen with large numbers of patients taking the drugs over a long period of time.

Earlier this week Centocor, Inc., maker of Remicade, announced that it's strengthening its prescribing information to instruct patients to be tested for tuberculosis before beginning treatment with the drug. The company reports 84 cases of tuberculosis that have been picked up after starting treatment with Remicade out of 170,000 patients treated worldwide. Fifty-two of the cases occurred in Europe.

"It's significant that the TB occurred during the first six infusions, the first few months of therapy," Dr. E. William St. Clair of Duke University Medical Center told CNN. "Most likely it's the activation of latent TB. I think it's prudent to give a skin test to everyone before starting Remicade to see who's been exposed to TB in the past and treat them with anti-TB therapy."

St. Clair speculates that most cases occurred in Germany and countries surrounding the Mediterranean in people over age 60 who experienced poor living conditions post-war and could have been infected with TB at that time. It's not clear why the higher tuberculosis infection rate is seen in patients taking Remicade and not in those taking Enbrel.

"It could be the patient population. I suspect more patients in Europe are treated with Remicade because of the drugs available there," said St. Clair, "and it could be difference in mechanism between the two drugs."

Another concern with this new class of drugs is possible demyelination, which is a type of nerve damage often seen in multiple sclerosis.

"This is a new side effect that's been described in the last year," said Klippel. "The number is very, very small and the medical community is aware of the risk."

"We have to make sure patients are educated about this possible side effect," said St. Clair. "Any neurological side effects should be discussed with the physician."

Sources say the FDA will also be looking at the possible risk of the cancer lymphoma in patients taking these drugs.

"Rheumatoid arthritis patients are more prone to this cancer and appears to be due to the underlying disease," said Dr. Leslie Garrison, senior vice president of clinical R & D with Immunex, the maker of Enbrel. "What we've seen so far appears to be within the rate of rheumatoid arthritis patients."

Dr. Hayes Wilson of Piedmont Rheumatology in Atlanta says he's treated patients with both Remicade and Enbrel and has not seen any of these problems.

"We have to inform our patients," said Wilson, "but I don't want to discourage them and unfortunately this may cause some to give up on a medication that can potentially help them."