Black box warning on top of black box warning…and patients keep dying

Law & Disorder

If this e-Alert were a police procedural show, in today’s opening scene Enbrel would be brought into the homicide department for questioning. And some hard-as-nails veteran detective would say something like, “This guy’s got a rap sheet a mile long.”

Enbrel? Ring a bell? For longtime e-Alert readers it probably rings half-a-dozen bells.

Drawing the line

Enbrel is in a class of drugs known as TNF-alpha blockers. These drugs (which include Remicade, Cimzia, and Humira) inhibit the body’s natural immune response in order to treat immune system dysfunctions such as rheumatoid arthritis, psoriasis, and Crohn’s disease.

But the risk here is obvious: When you solve a problem by suppressing the immune system, you open the door to a wide variety of infections.

Which brings us to Enbrel’s rap sheet of potential adverse reactions:

  • Tuberculosis
  • Bacterial sepsis
  • Nervous system disorders
  • Congestive heart failure
  • Cancer

Year after year, one study after another has revealed exactly how dangerous this drug really is. And of course, the FDA long ago required a “black box” warning for Enbrel and other TNF-alpha blockers.

Riiiight. The dreaded black box. In Drug World, the black box is considered a big deal. But what is it really? Get out a black-ink pen and draw a rectangle. How does that look? Pretty forbidding? No. Pretty lame. When you consider that many patients have died due to adverse reactions from these drugs, a thin black line is literally the very LEAST the FDA can do.

Another warning…another drug…another warning

Earlier this month, the FDA announced yet another new warning for Enbrel and other TNF-ab drugs.

To the rap sheet we can now add a lethal fungal infection called histoplasmosis.

I have to admit, I’m impressed by the way the FDA initially acted on this one. Apparently someone at the agency followed up on a single case of the fungal infection and found evidence that TNF-ab drugs may have been linked to 45 deaths in patients who developed the infection.

And can you guess where this is going? Yep: another black box warning.

Now you might think that at some point the FDA would throw in the towel and say, “You know what? This stuff actually kills people. We better take it off the market.” But three of the four TNF-ab drugs make more than $1 billion per year. And if you’re raking in that kind of crazy money, your drug doesn’t get pulled unless it’s killing nearly everyone who takes it.

So the FDA is going in another direction.

According to the Associated Press, the agency advises doctors to consider “aggressive use” of antifungal drugs in patients who develop flu-like symptoms associated with the infection. And what’s wrong with THIS picture? One FDA official told the AP that antifungal drugs also have dangerous side effects.

He added that if a patient develops a fungal infection, doctors “should consider” stopping treatment with Enbrel and other TNF-ab drugs.

Don’t STOP treatment! Geez, don’t do anything rash! But, you know, consider it.

Rheumatoid arthritis patients might consider other directions as well.

In the e-Alert “Liquid Gold” (11/16/05), I told you about a study that demonstrated how four teaspoons of extra virgin olive oil taken daily for 12 weeks reduced pain and morning stiffness among RA patients.

And in the e-Alert “Burning Down the House” (3/25/03), I told you about a supplement called Wobenzyme, which contains a blend of pancreatic enzymes that reduce RA symptoms by lowering abnormally high levels of antibodies (produced by an overactive immune system) that prompt RA inflammation.

Talk to your doctor before treating rheumatoid arthritis with Wobenzyme or olive oil.

“FDA Orders Stronger Warnings for 4 Arthritis Drugs” Ricardo Alonso-Zaldivar, Associated Press, 9/5/08,