WEDNESDAY, June 4 (HealthDay News) -- U.S. health officials have started a safety review of a class of drugs known as tumor necrosis factor (TNF) blockers, which are widely prescribed to treat autoimmune disorders such as rheumatoid arthritis, juvenile rheumatoid arthritis and Crohn's disease.

The announcement did not come as a surprise, as experts have long debated the risk-benefit profile of the drugs without coming to any consensus.

Among the chief concerns being investigated by the U.S. Food and Drug Administration are whether the drugs are associated with the development of cancer, especially lymphoma, in children and young adults being treated for rheumatoid arthritis or Crohn's disease. The agency is investigating about 30 reports of cancer in this younger age group submitted between 1998, after the approval of the first TNF blocker, through April of this year. TNF blockers have also been linked to an increased risk of infection.

"I think it's a fair thing to say this is an area of ongoing concern that has not been resolved. It's not something new," said Dr. Chaim Putterman, chief of the division of rheumatology at Montefiore Medical Center and Albert Einstein College of Medicine in New York City. "[The drugs] were approved in adults, and more drugs are coming out, and everyone would prefer an indication in children, so the FDA has decided to clear it. It has always been a concern, and it's something that should be clarified."

Four TNF blockers are currently approved in the United States: Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab) and Cimzia (certolizumab). Remicade is approved for use in children with Crohn's disease. Enbrel and Humira are approved to treat children with juvenile rheumatoid arthritis, according to the FDA.

The FDA review is focusing on the first three. All four are approved for multiple indications.

TNF blockers work by dampening the immune system, which becomes hyperactive in patients with rheumatoid arthritis.

The drugs have clear benefits, according to experts, and have revolutionized the treatment of some of these diseases.

"One of the reasons that these medications have such a market despite the concerns is that they are so remarkably effective," Putterman said. "There are not only subjective benefits but a tremendous amount of objective evidence, not only in inflammation and patient symptoms, but also in disease progression. These drugs have really addressed a previously unmet need."

"These drugs are probably the most important advance in the treatment of rheumatoid disorders in the last 20 to 30 years. They dramatically improve certain forms of crippling arthritis and almost stop them. Some people go from being in a wheelchair [to] jumping up and walking around," said Dr. Stephen Lindsey, head of rheumatology at Ochsner Health Service in Baton Rouge, La. "They're being used earlier and earlier, because they're so good. I think the FDA is being cautious. I think it's smart. What are the risks of a child being crippled and non-functioning versus the risk of cancer? Maybe, in odd cases, we need to think more and not jump in with all four limbs."

The increased risk for cancer may also be a result of factors other than the drug. "The signal [for cancer] has not been a dramatic one," Putterman said. "There are confounding factors in rheumatoid arthritis patients, which can make interpretation of the data more difficult."

One confounding factor is that rheumatoid arthritis patients, independent of treatment, have a higher risk of some cancers, and some patients have also been treated with methotrexate, a chemotherapy agent that has a known association with lymphoma.

And then there's the conflicting scientific evidence. One 2006 study reported that concerns about TNF blockers causing cancer were unfounded. But earlier this year, a review of the research concluded the risk may be real.

"TNF plays an important role in immune surveillance and, by blocking it, you might be interfering with the body's own defenses," Putterman said.

The FDA has requested that makers of TNF blockers approved for use in children and young adults supply information about all reported cases of cancer in children and young adults taking the drugs.

The maker of Cimzia, UCB Inc., must conduct a study looking at the long-term risks of this drug. That study will begin in 2009, and will take about a decade to complete.

In the meantime, the FDA has asked health-care professionals to weigh the possible risks against the benefits when prescribing TNF blockers.

More information

Read about TNF blockers U.S. Food and Drug Administration.