FDA reviews tumor necrosis factor blockers: Scrutiny may worry some patients, derms say

July 1, 2008

The ongoing Food and Drug Administration (FDA) review of TNF-blocking biologic drugs is unlikely to have much impact on dermatologists' use of these drugs, physicians say.

Key Points

National report - The ongoing Food and Drug Administration (FDA) review of TNF-blocking biologic drugs is unlikely to have much impact on dermatologists' use of these drugs, physicians say.

While they welcome the FDA's scrutiny as a means of quantifying any cancer risks associated with TNF blockers, some worry it could needlessly frighten patients and their families.

On June 4, the FDA announced it was investigating the possible association between Remicade (infliximab, Centocor), Enbrel (etanercept, Amgen/Wyeth), Humira (adalimumab, Abbott) and Cimzia (certolizumab, UCB) and the development of lymphoma and other cancers in children and young adults.

"These reports describe cancer occurring in children and young adults who began taking TNF blockers (along with other immunosuppressive medicines, such as methotrexate, azathioprine or 6-mercaptopurine) when they were ages 18 or less, to treat juvenile idiopathic arthritis (JIA, formerly called juvenile rheumatoid arthritis), Crohn's disease or other diseases," the release says.

FDA reviews: How may patients react?

These other diseases included ankylosing spondylitis, psoriatic arthropathy, ulcerative colitis, uveitis and sarcoidosis, FDA spokeswoman, Crystal Rice, tells Dermatology Times.

A few of the other diseases under treatment were not known, she says, but no reports cited treatment for psoriasis alone.

As such, the review means very little for dermatologists and their patients, says Steven R. Feldman, M.D., Ph.D., professor of dermatology, pathology and public health sciences, Wake Forest University.

"In dermatology," he says, "we don't use the TNF inhibitors with azathioprine or 6-mercaptopurine - at least, not normally.

"We occasionally use them with methotrexate in adults," but very rarely in children.

"If a kid has horrific, total, unrelenting psoriasis that doesn't improve with a TNF inhibitor alone, but does with a TNF inhibitor plus methotrexate," Dr. Feldman says, "it's probably worth taking whatever small cancer risk there may be."

Similarly, Lawrence F. Eichenfield, M.D., says the review probably won't alter the desire of most patients with moderate-to-severe disease that doesn't respond to topical agents and/or phototherapy to use TNF inhibitors.

Dr. Eichenfield is chief of pediatric and adolescent dermatology and professor of pediatrics and medicine (dermatology) at Rady Children's Hospital, University of California, San Diego, School of Medicine.

Over time, he says, physicians will begin considering the duration of therapy, the number of courses they prescribe with different biologic agents and how these factors may influence cancer development.

Benefits of review

Accordingly, sources say they'd welcome more information about how TNF blockers - used alone and with traditional systemic agents - impact cancer development.

"Most of us who use these medications frequently understand the review is actually beneficial, because it will help us to further understand them," says Jeffrey M. Weinberg, M.D., assistant clinical professor of dermatology, Columbia University.

However, he says the review will prompt some dermatologists to alter their prescribing habits "if it reinforces their concerns about these drugs."

Historically, Dr. Eichenfield says, "Systemic therapy for psoriasis, whether in adults or children, revolves around immunosuppressive medications, many of which are known to be associated with an increased risk of cancer."

And since many of the reported cancers occurred in patients who were taking multiple immunosuppressants, Dr. Eichenfield says, "It's unclear how monotherapy with different TNF blockers might impact the development of cancer over time, compared to patients who have had either serial or concurrent immunosuppressive therapy."