Progressive multifocal leukoencephalopathy (PML), a life-threatening brain disease caused by activation of an otherwise harmless virus, is an example. Dr. Fraenkel says that a handful of people with RA have developed PML on the biologic drug rituximab (Rituxan). She estimates the risk to be about 3 in 100,000. However, she notes, “just as many people with lupus have developed PML and have never been on biologics, but have been treated with cyclophosphamide,” a drug to treat kidney disease and other conditions. 

The occurrence of PML with rituximab has resulted in a black box warning due to the way serious side effects are now reported to the Food and Drug Administration. Cyclophosphamide, an older drug that predates the new safety reporting procedures, doesn’t carry the warning.

“Patients are much more frightened by newer drugs that are associated with these rare, serious side effects because of the different ways of reporting,” says Dr. Fraenkel. “But the uncertainties surrounding the side effects are the same.”

Take Steps to Reduce Risks

Just because a drug comes with certain risks doesn’t mean there’s nothing you can do about them. Many serious side effects can be reduced or prevented through smart strategies and a collaborative effort between you and your doctor.

Some side effects are silent. Others may start out so small they aren’t noticed. Simple lab tests and exams often can spot early signs of a problem so measures can be taken to avoid or minimize the problem. For example:

  • Because methotrexate can affect the liver, RA treatment guidelines recommend testing for liver problems before starting and regularly while using methotrexate. To reduce the risk of liver problems, talk to your doctor about supplementing with folic acid.
  • Osteoporosis is a major risk of long-term corticosteroid use. Guidelines recommend assessing total risk for bone loss (from all causes, including corticosteroids) and monitoring bone mineral density when corticosteroids are used for three months or longer. If corticosteroids cannot be stopped and you are at risk for complications from bone loss, talk with your doctor about options for supporting bone health, such as medications, supplements and lifestyle changes.
  • There is now good evidence that biologic agents do not increase the risk of most cancers, including lymphoma. However, they do appear to increase the risk of skin cancer, so people taking biologics should see a dermatologist at least yearly for a thorough exam.