Enbrel and the Mystery of the Black Box Warning

Health Professional

No, this is not the title of a Nancy Drew novel that begs solving.

But I have had many patients asking me about the significance of the black box warning on Enbrel. And why was there no black box warning before this?

Well, to review the facts of this case, up until recently, Enbrel was alone among the anti-tumor necrosis factor drugs (TNF inhibitors) in not having a black box warning regarding risks of tuberculosis (and other infections).   However, these same dangers had previously been printed in bold-face type on Enbrel's package insert.

The black box warning includes additional language regarding screening and monitoring patients for tuberculosis.   It also states that studies suggest that the risk of reactivation of latent tuberculosis infection is lower with Enbrel than with tumor necrosis factor-blocking monoclonal antibodies -- the drugs Humira and Remicade, in particular.

Enbrel, on the other hand, is a fully human soluble tumor necrosis factor receptor.

Clinical studies enrolling more than 20,000 patients worldwide have shown cases of tuberculosis in about 0.01% of patients treated with Enbrel.   In trials involving more than 15,000 patients in the United States and Canada, about 0.007% of those patients treated with Enbrel developed tuberculosis. In plain English, just 1 out of 15,000 patients developed tuberculosis.

But despite the small number, serious infections, including tuberculosis, have happened in patients taking Enbrel.   And some of these infections have been fatal.

However, most of these infections have occurred in patients more susceptible to infection, including patients with poorly controlled diabetes.

It is important for any patient to report to their doctor any signs of infection, such as fever or cough.

Despite this new black box warning, we should all remember that Enbrel has been a very effective drug for patients with rheumatoid arthritis and many other illnesses.   It has been on the market since 1998, and I have many patients who have been taking that drug for most of the last decade; both patient and doctor are very happy with the results.

If your doctor does decide to place you on any tumor necrosis factor-inhibiting drugs --Humira, Enbrel or Remicade -- make sure he or she addresses the infection risk with you.   For most patients, this will include tuberculosis skin testing prior to beginning one of these drugs.

If a patient is positive for the tuberculosis skin test, that is not a contraindication to treatment with the tumor necrosis factor-inhibiting drugs.   It might mean the patient will have to take tuberculosis medications for a few months.   But it should only delay the initiation of Enbrel,  Humira or Remicade for one or two months.

Enbrel's inclusion in the Black Box Club should not deter its use in the overwhelming majority of rheumatoid arthritis patients.

Black box or no, these are all excellent drugs for treating rheumatoid arthritis.

There are many patients and doctors very grateful for these medications.   These drugs have made a profound difference in the lives of many.

See also:

FDA reviewing Humira, Remicade and Enbrel for cancer risk