A meta-analysis links tumor necrosis factor-alpha inhibitors, also called anti-TNFs or TNF blockers, to a higher incidence of skin cancer, but not to an increase in the risk of other cancers.

A type of biologic drug, all of which interfere with the immune system, TNF blockers are used to treat rheumatoid arthritis, or RA, as well as ankylosing spondylitis, psoriatic arthritis and polyarticular juvenile idiopathic arthritis. Drugs in this class include infliximab, or Remicade; etanercept, or Enbrel; adalimumab, or Humira; certolizumab pegol, or Cimzia; and golimumab; or Simponi.

“Doctors can be reassured that there doesn’t look like there’s an increase in [most] cancers,” says the lead author of the analysis, Xavier Mariette, MD, PhD. However, the medical community needs to be cautious about the increased risk of skin cancer – particularly for people who live in sunny climates, says Dr. Mariette, professor of rheumatology and head of the rheumatology department at Bicêtre Hospital and Paris South University, in France.

The findings, published in 2011 in the Annals of Rheumatic Diseases, add to the body of information about whether TNF blockers increase the risk of cancer, which has been an issue of much concern and debate among patients and doctors. Since biologics are relatively new – dating back to a little more than 10 years – there is no long-term data, and any cancer link could take many years to show up. Clouding the picture is the fact that people with inflammatory arthritis, especially RA, are at higher risk of developing certain cancers.

The meta-analysis pooled the results of almost 30 previously published studies and study summaries on TNF blockers and different types of cancer. Among the studies that looked at skin cancer, the researchers calculated that the risk of developing non-melanoma skin cancer was 45 percent higher among patients who received TNF blockers than those who didn’t. The risk of developing melanoma (the deadliest form of skin cancer) was 79 percent higher among patients on TNF blockers, but the results were based on only the two studies that looked at melanoma.

Among the other findings: There is no increase in cancer risk in patients who used anti-TNF drugs for longer periods or in people who had previously had cancer more than five years before..

Patients who have had cancer in the past are often excluded from clinical trials of these drugs, because they already have an elevated risk for getting the same or another form of cancer again. Doctors may avoid prescribing TNF blockers to these patients for fear of further increasing the risk. With more study in this area, Dr. Mariette says doctors may be comfortable prescribing these drugs to arthritis patients who have been cancer-free for at least five years. “We couldn’t entertain that five years ago,” he says.

Arthur Kavanaugh, MD, a rheumatologist and professor of medicine at the University of California, San Diego, says this latest analysis will not substantially change the way he prescribes TNF blockers for his RA patients.

“I discuss this with patients already. We discuss cancer a lot because it is such an important issue and it is a theoretical consideration with any medications that affect normal immune function,” Dr. Kavanaugh says. “When I discuss it with them, I say that we don’t know if there is an increased risk, but because it is possible, they need to accept the fact that there may be.”

He adds, “While data from controlled clinical trials is of great importance, it is not always possible to extrapolate to the broader population. For example, in a clinical trial, patients tend to be scrutinized more regularly and perhaps more thoroughly for safety issues, and as a result, things may be detected at an earlier stage than they may be in the clinic.”

Nevertheless, Dr. Kavanaugh says the additional data may help doctors and patients make informed decisions.

“Safety information is always important,” Dr. Kavanaugh says. “We try to bring as much information as possible, including data from analyses such as these, to the patients, and talk to them about the possibilities. In the end, patients want to know how likely is it that it will happen to them, and of course for an individual person it is not possible to predict.”