Two studies have found no link between an increased risk of cancer and tumor necrosis factor-alpha inhibitors, or anti-TNFs, a type of biologic drug.

Biologics, including anti-TNFs, work by interfering with parts of the immune system to decrease inflammation, a central feature of rheumatoid arthritis, or RA. Because of this, there has been concern that anti-TNFs and other biologics may increase patients’ cancer risk as well as their risk for serious infections.

In the first study, a meta-analysis published in Arthritis & Rheumatism, researchers reviewed six trials that included a total of 2,183 RA patients taking anti-TNFs and 1,236 taking methotrexate. The patients all had early-stage RA and had not been previously treated with methotrexate or other disease-modifying anti-rheumatic drugs, or DMARDs. The duration of the trials were between six and 12 months.

The analysis found that 19 people taking at least one dose of an anti-TNF, including adalimumab, or Humira; etanercept, or Enbrel; and infliximab, or Remicade, developed a malignancy compared with 10 patients taking methotrexate. Researchers concluded there was no significant difference in risk.

The second study, presented at the 2011 European League Against Rheumatism conference in London, looked at more than 13,600 Danish patients, the majority of whom had RA, from the DANBIO registry, a nationwide database that includes all rheumatic patients receiving biological drugs. From January 2000 to the end of 2008, almost 5,600 of them had started anti-TNF treatment.

The researchers cross-referenced data from DANBIO registry with the Danish Cancer Registry and found that 181 patients ever treated with an anti-TNF developed cancer compared to 132 patients who had not taken an anti-TNF. The researchers concluded there was no statistical difference in cancer risk. After further analyzing the data, the researchers also concluded that the risk of cancer did not rise with longer-term use of anti-TNFs.

“This is a reassuring reinforcement of previous data,” says Daniel Furst, MD, professor of rheumatology at University of California, Los Angeles.

Research from 2006 in the Journal of the American Medical Association found the likelihood of malignancies was greater in people taking higher doses of anti-TNF medications than those receiving lower doses.

But Dr. Furst suggests this could be a chicken-and-egg issue: Previous research has shown that people with RA, independent of medication use, have a higher risk of cancer than people without the disease. This is possibly due to chronic stimulation of the immune system. “People who have the most disease activity are those who will get higher doses of anti-TNFs, and they already have the highest probability of getting [cancer].”

Dr. Furst says there is a sense that if you suppress immune activity, it increases the risk of cancer, but there isn’t a lot of research to support it.

A 2009 study came to the same conclusion as the two new studies that show anti-TNF drugs do not raise cancer risk. One of the largest and longest population-based assessments of cancer risks associated with immunosuppressive therapy, published in Arthritis & Rheumatism in 2009, compared cancer rates among more than 75,000 RA patients in Sweden who were taking either no medications, methotrexate, anti-TNF therapies or other DMARDs. In the six-year period they analyzed, the researchers found the risk of developing cancer was the same for people on anti-TNF medications as those in the other groups.

One reason for the uncertainty of the connection between biologic drugs and cancer is that the drugs have not been around that long; etanercept, the first biologic, was approved in 1998.

It is best to have at least 20 years of background on medications, but that isn’t always possible, says Thomas Lehman, MD, professor of pediatrics and chief of the division of pediatric rheumatism at the Hospital for Special Surgery in New York City. He adds that the U.S. Food and Drug Administration closely monitors newer drugs for potential problems. And with cancer there isn’t yet a clear indication, so the issue is still not settled.

Dr. Furst believes the benefits of these medications outweigh any risks for most patients. And he says that when he educates his patients about anti-TNF risks, 90 percent say, “Thank you, let’s move on.”