The numbers can fool you. How numbers are presented makes a difference in a patient’s perception. For example, the risk for tuberculosis (TB) in the general U.S. population is 2.8 in 100,000; among people taking TNF inhibitors it is 49 in 100,000, according to one study. “TNF inhibitors cause a 17.5-fold increase in risk for TB,” is a way of describing the relative risk, and it sounds a lot scarier than “The risk of TB is 0.05 percent among people taking TNF inhibitors,” a way of describing the absolute – or actual – risk.

Here’s another example: Methotrexate, a mainstay disease-modifying antirheumatic drug (DMARD) for treating rheumatoid arthritis (RA) and juvenile arthritis, is associated with a 3 percent risk of serious infection, meaning 3 in 100 people treated with the drug for a year get a serious infection. If a biologic drug, specifically a TNF-alpha inhibitor, is added to methotrexate, the risk increases to 5 percent – meaning 5 in 100 people treated with both drugs get a serious infection.

This can be reported in terms of relative risk: “a 60 percent increase in the risk of a serious infection.” Or it can be reported as absolute risk: “An additional 2 in 100 people, or 2 percent, develop a serious infection.” Again, the former example is more intimidating.

“Just knowing there is a ‘significantly increased risk of infection,’ doesn’t provide much context,” says Dr. Curtis. But it can make some patients hesitant about adding a biologic to their methotrexate therapy, although the more aggressive approach could be key to shutting down pain and preventing joint deformity.

The drug seems worse than the disease. For many serious side effects, it’s unclear exactly what role the drug plays. Sometimes, the disease itself puts a person at risk for certain problems, with more severe disease equaling bigger risk. RA increases the risk of serious infection, including infections that require hospitalization, making it difficult to determine to what extent biologic agents, like TNF inhibitors, may further increase the risk.

Age, other health problems and other medications also can increase the risk of certain side effects. Studies show that having diabetes or chronic lung disease or taking corticosteroids also worsens the risk of serious infection in people taking biologic agents.

“There’s much uncertainty about the rare side effects that we blame on drugs, but truthfully, we don’t know if there is a causal association,” says Liana Fraenkel, MD, an associate professor of medicine, practicing rheumatologist and researcher at Yale School of Medicine in New Haven, CT. Some of Dr. Fraenkel’s research on this has been funded by the Arthritis Foundation.

Newer drugs list more risks. In recent years, the FDA has made sweeping changes to its drug safety program in an effort to better inform consumers about possible risks. Some of these changes were made possible by 2007 legislation authorizing the FDA to monitor and report on the safety of new drugs more rigorously. From 2000 to 2010, the FDA’s public database of reported side effects grew from 200,000 to nearly 700,000. As a result, newer drugs may have a longer list of side effects than older ones – but that doesn’t mean that newer drugs are more risky.