The two letters are eerily similar. Both bear the circular logo of the pharmaceutical company, Centocor. Both carry dates in October 2001. Both are addressed to “Dear Healthcare Professional,” followed by a heading in large, bold, capital letters: IMPORTANT DRUG WARNING. And there’s one more important commonality: both contain information about serious risk from Centocor’s drug REMICADE , a medication widely used to treat Crohn’s disease and rheumatoid arthritis (RA).
The first letter, dated October 5, warns doctors that tuberculosis and “other opportunistic infections” have been observed in patients taking Remicade. At least 84 cases of TB have been documented, and 14 of those people have died as a result.
But then, less than two weeks later, came the second letter. It makes you wonder – is this just a bad coincidence or do we not know enough about what this drug can do?
Dated October 18, the second letter cautions doctors against prescribing Remicade to patients with congestive heart failure (CHF). In clinical trials, scientists found that patients’ moderate to severe CHF symptoms worsened while taking Remicade – and at least seven people died from CHF while participating in a Remicade clinical trial.
Your doctor may or may not have received both of these letters in October. And if you take Remicade, you may have already been informed. But if you or someone you love suffers from Crohn’s or RA, you need to understand these results right NOW.
REMICADE is the brand name for the prescription drug infliximab, which works by inhibiting the body’s natural immune response. Specifically, it binds an immune system cytokine called tumor necrosis factor (TNF). Inflammation is a common side effect of TNF activity (and other immune responses as well).
Both Crohn’s disease and rheumatoid arthritis (RA) are characterized by inflammation – the former in the gastrointestinal tract, and the latter throughout the body’s joints. So drugs like Remicade were designed to treat RA and Crohn’s by blocking the TNF activity that may contribute to the inflammation.
Remicade was first approved in 1998. It was indicated for short-term use in treating patients with Crohn’s that had not responded to other kinds of therapy. It was also approved for treating RA in combination with methotrexate, for patients who had not seen relief from methotrexate alone. (Methotrexate, also known as amethopterin or by the brand names Folex and Rheumatrex, is a prescription drug often used to treat RA. It comes with its own list of serious side effects, including problems with the kidneys, stomach, and liver, loss of hair, and increased risk of blood diseases like leukemia.)
Because of its immunosuppressive action, authorities knew that Remicade could increase the chances of developing infections. So the October 5 warning about the risks of tuberculosis, histoplasmosis, listeriosis, and fungal pneumonia, was not a complete surprise. The new communication recommends that doctors test patients for latent TB infection before prescribing Remicade, and that they carefully consider risks in regions where histoplasmosis typically occurs. (Histoplasmosis is caused by the bacterium H. capsulatum, which is contracted through contact with soil or materials contaminated with bat or bird droppings. According to the Centers for Disease Control and Prevention, it is most prevalent in the eastern and central United States.)
But the second warning arose from Centocor’s own research. Animal studies had suggested that Remicade’s TNF-binding action might also be an effective therapy against congestive heart failure (CHF). This deadly condition results when the heart cannot pump efficiently, usually as the result of damage from a heart attack or years of chronic hypertension or heart disease. Fluid accumulates in the lungs and leads to breathing difficulties and leg and ankle swelling. Almost five million Americans have congestive heart failure, and most of them die from it eventually.
So Centocor recruited a total of 150 patients with moderate to severe congestive heart failure for the trial. A control group of 49 people took a placebo, while 101 received Remicade, either in a 5 mg/kg or 10 mg/kg dosage. All of the drugs were administered intravenously, and the treatments lasted for six weeks.
During the study, seven of the 101 patients in the Remicade group died of congestive heart failure. (None of the patients in the placebo group died during the study.) A 7 percent death rate in 6 weeks was significant enough for Remicade’s manufacturer to halt the study and report the findings to the FDA.
The result was the October 18 letter, which was mailed to 35,000 doctors who the FDA determined were “likely to treat” patients who may be at risk.
We can only hope that the information reached all the appropriate doctors – and all the appropriate patients. Centocor says it is working with the FDA to develop updated prescribing information and packaging for the drug. (Maybe they were able to catch it before it went off to the printer – the boxed warning notice had just been revised to reflect the increased risk of tuberculosis and other infections.)
Here’s what you can do:
- If you take Remicade, discuss these risks with your doctor. Ask for a TB test, and ask about the risk of histoplasmosis in your area. If you have congestive heart failure as well, ask about other alternatives to Remicade.
- Pass this information along to anyone you know who might already be taking Remicade, and to anyone who suffers with RA or Crohn’s and might be prescribed the drug in the future.
But perhaps most importantly, remember that prescription drugs and their potentially toxic side effects are not the only option for patients with Crohn’s and RA. At HSI, we’ve written extensively about alternative therapies for both RA and Crohn’s disease. In February 2001 Member’s Alert newsletter, we told you about an oral supplement from Germany called Wobenzyme, a blend of pancreatic enzymes that clears the body of the excess antibodies that characterize an autoimmune disease. Studies have shown that Wobenzyme can prevent RA flare-ups and help lower levels of these antibodies, called circulating immune complexes, or CICs. In October 2000, we wrote about the therapeutic yeast saccharomyces boulardii (SB), which nourishes and protects the healthy intestinal flora. At least two clinical studies have shown that SB can significantly reduce Crohn’s symptoms compared to placebo.
Centocor reminds us that approximately 170,000 patients have been treated with Remicade worldwide since it was introduced. And between these two incidents, only 21 people have died – 14 from infections and seven from congestive heart failure. The “Dear Doctor” letter also notes that “most” of the people who died of TB were taking other immunosuppressive drugs while taking Remicade. It’s true that the risks are small – but that’s no comfort to the families of those 21 people. Before you start – or continue – to take any prescription medication, make sure you have all the information and know all the risks. The FDA’s not going to send YOU a letter – but here at HSI, we’ll keep doing our part by informing you of the risks as we discover them and by helping you take control of your health.
Copyright 1997-2002 by Institute of Health Sciences, L.L.C.
