Some biologic drugs taken by children to treat inflammatory disorders, such as juvenile rheumatoid arthritis and Crohn’s disease, increase the risk of cancer and should carry stronger, boxed warnings about that risk in their prescribing information, federal regulators said in 2009.
The Food and Drug Administration (FDA) is directing manufacturers of a class of biologic drugs known as tumor necrosis factor alpha blockers, or TNF-alpha blockers, to highlight the increased risk of cancer, particularly lymphoma, in children and adolescents who take these kinds of medications.
TNF-alpha blockers include infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), certolizumab pegol (Cimzia) and golimumab (Simponi).
Tumor necrosis factor alpha is a protein that is an important part of the body’s normal immune response. When TNF-alpha is overproduced, however, it can trigger unchecked inflammation, which may damage the joints and other organs.
Medications that neutralize TNF-alpha help to control inflammatory diseases, but they also suppress the body’s natural defenses, leaving patients vulnerable to infections and other threats, including cancer.
The new warnings resulted from an investigation that the FDA launched last year into reports of cancer in children and young adults submitted to the agency’s Adverse Event Reporting System over a 10-year period.
The agency said it found that TNF-blockers increased the risk of cancer, and that the cancers appeared an average of 30 months after starting treatment. About half of the cancers identified were lymphomas, a type of cancer that involves cells of the immune system. Some of the cancers were fatal.
In completing their safety review, regulators said they also found new risks associated with the use of these drugs, including increases in cases of leukemia and psoriasis.
"I think it’s a very scary thing for parents," says Barbara Adams, MD, director of pediatric rheumatology at the University of Michigan Hospitals in Ann Arbor. "And I think it’s a very difficult decision to make because when we propose the TNF-alpha inhibitors, it’s because the children really need them to grow and develop and do everything else other children can do."
Dr. Adams says the new warnings would probably not change the way she prescribes these kinds of drugs, because she uses them as a treatment of last resort for kids who are in danger of permanent joint damage, blindness and lasting disability.
In those cases, she said, the small increase in the risk of cancer would not be likely to outweigh the great benefits of the medications.
"If a child’s risk of cancer is represented by 100 happy faces and we add five or six sad faces to it, that’s a relatively small increase in risk," says Dr. Adams.
But she says the new warnings are important and underscore the importance of using the medications judiciously.
"I think that one of the things that I would hope that physicians and pediatric rheumatologists are not using this drugs in a casual way," says Dr. Adams, who is a member of Arthritis Today's medical advisory board. "That they are quite sure that children need them."
Dr. Adams also said that the new warnings make it all the more important for parents and physicians to closely monitor children who take TNF-alpha blockers.
"Not all physicians believe you need to monitor blood counts and other factors in these kids on a very regular basis," Dr. Adams says. "Since we’ve become so comfortable with some of these medications, there’s a casualness about monitoring. It’s going to make all of us more careful about monitoring blood counts, about doing careful physical exams on a regular basis, that we’re screening patients for the possibility of cancers."