FDA Wants Tougher Warnings On TNF-Inhibitors
7 CommentsBy Ed Silverman // September 4th, 2008 // 11:48 am
The agency say the manufacturers of Humira, Cimzia, Enbrel, and Remicade must strengthen existing warnings in the prescribing info and medication guides due to risks of developing histoplasmosis, an opportunistic fungal infection. Most of the cases in the Ohio River and Mississippi River valleys and in at least 21 of those, the infection wasn’t initially recognized. Twelve patients died.
The four drugs, known as tumor necrosis factor alpha blockers, or TNF-inhibitors, which suppress the immune system, are approved to treat such conditions as rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, plaque psoriasis, ankylosing spondylitis, and Crohn’s disease. Humira is made by Abbott; Cimzia is made by UCB; Enbrel is sold by Amgen and Remicade is sold by Johnson & Johnson.
“Under the FDA’s new authorities, we can require safety label changes and a risk evaluation and mitigation strategy, known as REMS, when the agency becomes aware of new safety information,” Bob Rappaport, director of the FDA’s division of anesthesia, analgesia and rheumatology products in the Center for Drug Evaluation and Research, says in a statement.
Since the initial approval of the four TNF blockers, the FDA notes the prescribing info has included info about the risk of serious infections, including fungal infections. However, based on reports reviewed by FDA, the agency says health care professionals are not consistently recognizing cases of histoplasmosis and other invasive fungal infections, leading to delays in treatment.
The FDA says patients taking TNF blockers should be aware they are more susceptible to serious fungal infections. The agency reviewed one reported case of histoplasmosis in a patient taking Cimzia. The FDA, by the way, also received reports of cases of coccidioidomycosis and blastomycosis, including deaths, in patients treated with TNF blockers.
Meanwhile, the FDA notes that the manufacturers are required to submit safety labeling changes, including strengthened warnings and revisions to the Medication Guides to the FDA within 30 days or to provide a reason why they do not believe labeling changes are necessary.
If they do not submit new language, or if the FDA disagrees with the new language the company proposes, the Food and Drug Administration Amendments Act of 2007 provides strict timelines for resolving the labeling changes and allows the agency to issue an order directing the labeling change as deemed appropriate to address the new safety information.
Medication Guides will become part of a REMS for Humira and Remicade and are already part of a REMS for Enbrel and Cimzia. The manufacturers for all four of these drugs will also be required to educate prescribers about the risks.
UPDATE: Amgen sends us this statement.
Ger
On this latest FDA warning of further adverse events associated with anti-TNF drugs such as etanercept (enbrel); we are once again challenged:
Should Dr. Edward Tobinick (dermatologist) be allowed to continue to expose vulnerable Alzheimer’s disease patients to the off-label use of etanercept (enbrel), solely based on the extraordinary claims of Dr. Edward Tobinick (dermatologist). I invite you to acquaint yourselves with Ed’s excellent story on Dr. Tobinick, along with in-depth research contained in the over 180 comments section accompanying the story:
Enbrel, Alzheimer’s And A Controversial Doctor
“http://www.pharmalot.com/2008/07/enbrel-alzheimers-and-a-controversial-doctor/
Sonali
Good artical
Robert
Why is Ger ignoring all of the scientific evidence, and the scientific
opinions of the reviewers from Nature Clinical Practice Neurology;
Janssen; the Journal of Neuroinflammation; BMC Neurology, etc.? All
breakthroughs meet scientific resistance at first. But what are Ger’s
credentials? He is interfering with the proper scientific
consideration of these findings, and thereby interfering with a
promising treatment for millions of people. His actions are costing
lives. Why is he not asking for further study?
Robert
JAM
My daughter has been on two of the TNF-inhibitors, Enbrel and Humira, for three of the past four years for moderate-to-severe plaque and guttate psoriasis. she has had recurrent candidal infections and now has a persistent cough, intermittent stabbing abdominal pain with tender nodules, and flu-like symptoms. We stopped all TNF-inhibitors, but cannot get any doctors to listen to us or check her for a systemic fungal illness. She is unable to work, unable to attend college full-time. We have seen dermatologists, infectious disease experts, and rheumatologists. The last doctor kind of scoffed at our suspicions and said, “oh, you read the article, did you?” We’re from the Ohio River Valley and my daughter spent time in New Orleans helping with Katrina clean-up. any ideas how I can get a doctor to listen?
Justice in MI
JAM - If you can get to Ann Arbor, MI - Dr. Carol Chenoweth, Professor of Internal Medicine, Infectious Disease. She is brilliant, thorough, and caring. Google her.
Nancy
From 2001 until December 2005, my husband, Lewis Stroup, took Remicade, Enbrel, and Humira for RA. In February 2005 he was diagnosed with monoclonal protein in his blood. Then, on March 8, 2007, he was diagnosed with Non Hodgkin’s Mantle Cell Lymphoma. He began taking the drugs before Johnson and Johnson, i.e. Centocor, Abbott, and Amgen/Wyeth announced that TNF Inhibitors could cause Lymphoma. Upon diagnosis, my husband was given 6 to 8 months to live; however, he had a Stem Cell Transplant on August 27, 2007, at Wake Forest Medical Center, Winston-Salem, NC. He continues to take Chemo for this deadly disease. His last CT Scan still shows tumors in his abdominal area. Our family and especially Lewis, have been and are still going through a nightmare over these drugs. Everyone needs to be aware of what these TNF Inhibitors can do to them. This should not be happening to him.
The doctor knows these drugs caused deadly Lymphoma in my husband. He and his sister are within one year in age, they both have the same genes and the same degree of RA. Lewis was treated with these three drugs and his sister wasn’t. Lewis has Non-Hodgkin’s Mantle Cell Lymphoma and his sister doesn’t. Unique case, proof that the drugs caused the Lymphoma. His doctor has written three letters stating that he believes that the TNF Inhibitors caused the Lymphoma because his sister did not take the drugs and she is fine.
The truth about TNF Inhibitors should have been shared with RA victims earlier. Remicade, Enbrel, and Humira are KILLER drugs. This is not fiction; this is a man’s life. One life is One too many.
Ingrid Kirschbaum
Hi, I am a 48 year old single mother of a 10 year old daughter, Dx with rheumatoid arthritis about 1996. I started ENBREL in 11/05 and since then:
Dx with atrial fib 6/06
dx with endometrial hyperplasia 8/06
hysterectomy and pelvic lymph nodes tested (clean) 11/06
blood issues (anemia, bleeding, etc) 3/07-7/07
atrial fib and congestive heart failure 11/07 (ejection fraction 20%)
atrial fib and tachycardia mediated cardiomyopathy 6/08
stage 3 Non-Hodgkins Lymphoma (large diffuse B Cell) 9/09 (while having CT scan for ablation to treat atrial fib).
chemo (R-CHOP) 10/08-3/09 Had to discontinue adriamycin after 3 rounds due to decreasing ejection fraction (from 50% down to about 30%).
3/09 went into cardiogenic shock and was put on inter aortic balloon pump, few days later had defib/pacemaker installed
2 weeks later wire lead poked through my heart muscle and I had pericardial effusion and had to have a new lead put in.
I know that these diseases have shortened my life, and I would like to know what is being done to warm people about these potential side affects. When I first started taking ENBREL, it only warned about tuberculosis and lymphoma. Now it warns for all the things that have gone wrong with me. I think that this was totally inappropriate treatment for me.
I have also just found out that my prescribing physician was on the UCLA staff that was participating in the clinical trials in 1999 and before.
The FDA is now looking into connections with ENBREL and childhood lymphomas…what about the adults who have already taken the ENBREL and now have had to endure lymphoma as well?
Thanks.
Ingrid