June 18, 2015
With a family history of breast cancer, Marcie Jacobs decided in June 2001 that an MRI screening was her best preventive option.
As is common with MRIs, Jacobs was injected beforehand with a contrast agent, a drug that helps sharpen the resulting images. But after a few of these treatments, she began noticing some strange cognitive effects. Jacobs began missing meetings. Over the next several years she had additional MRIs. The math skills that were crucial to her job as finance manager started deteriorating, she said.
Jacobs eventually wound up on disability. She stopped worrying about cancer – and started worrying about imaging drugs.
This month, two prominent experts in the radiology community joined in the concern, calling for more research into the possible health risks after three recent studies found that gadolinium, a potentially toxic metal, wound up in the brain tissue of MRI patients who used two different contrast agents.
Editorializing in the journal "Radiology," Dr. Emanuel Kanal at the University of Pittsburgh Medical Center, and Michael Tweedle at Ohio State University, said the studies "called into question" the "safety of at least some" of these agents. The two urged radiologists to change their prescribing habits, although not to stop using the drugs because of their proven benefits to patients. (Related video.)
Nine gadolinium-based contrast agents are sold in the United States. The two in question, Omniscan, made by GE Healthcare, and Magnevist, manufactured by Bayer HealthCare, once dominated the contrast agent market. Both GE and Bayer, in statements, said they were monitoring the issue and noted the new studies had not found any clinical impact, such as brain injury.
As ProPublica has reported, contrast agents like Omniscan had been on the market for years when, in 2006, they were linked to a crippling, sometimes fatal condition called nephrogenic systemic fibrosis, or NSF. The Food and Drug Administration put a "black box" warning on the drugs the following year, saying patients with kidney impairment may be at risk of NSF because they were unable to excrete the gadolinium.
ProPublica first disclosed in 2009 that the agency ignored two of its own medical reviewers who wanted to ban Omniscan for patients with severe kidney disease. In 2010, the FDA did act, recommending that GE's drug and two other agents shouldn't be used in patients with impaired kidneys. The other drugs were Magnevist and Optimark, sold by Mallinckrodt Pharmaceuticals.
The new studies cited by Kanal and Tweedle have set off alarms because they show that even patients with healthy kidneys are retaining gadolinium from Omniscan and Magnevist. Estimates are that about one-third of the 20 million MRIs in the United States each year use one of the nine contrast agents.
Doctors now routinely screen MRI patients for kidney problems before injecting them with contrast agents, and scientists believe that NSF has essentially disappeared. The new studies don't speak to the clinical effects, if any, of gadolinium in the brain. But in an interview, Kanal said the findings ought to make radiologists think twice about which agents to prescribe.
"We can use an agent today that does not retain gadolinium in the brain to the degree that those other agents do," he said, referring to Omniscan and Magnevist. Given that the alternatives are "at least as efficacious" as the other two, he asked, "Why are some still prescribing the agents that do accumulate in the brain over the other options?"
Jacobs has no medical proof, but she's convinced the two drugs are behind her problems.
As her symptoms worsened, Jacobs said she underwent a series of tests that found accumulated traces of gadolinium in her breast, thigh, liver and brain. Doctors were puzzled because she had no history of kidney disease and did not fit into the identified at-risk group.
She recovered old records and determined that she received Omniscan for her first 11 imagings and Magnevist before the last, in 2007. Jacobs said she eventually began a difficult, extended program to remove gadolinium from her body.
Researching on the Internet, Jacobs found a support group around the issue. Then in March, a radiology journal, Health Imaging, featured the group in an article on the new gadolinium research. That same month Jacobs started a Facebook group that is now composed of researchers as well as dozens of patients with similar gadolinium experiences and no evidence of kidney disease.
Jacobs said the new studies "confirm that the linear gadolinium-based contrasting agents such as GE's product Omniscan and Bayer's product Magnevist are being retained at much higher levels than radiologists and the FDA have acknowledged."
She hopes the FDA might pull the two agents from the market.
In a statement, an FDA spokesperson said the agency is "carefully reviewing" the new studies to "better understand the potential consequences to determine what further action is needed, which may include taking steps to ensure the public is aware of these preliminary findings."
Kanal, who has been advising the FDA and also chairs the American Board of MR Safety, said the new studies have "the entire international radiological community – and the FDA – on edge, as this is an entirely unanticipated finding."
GE Healthcare told ProPublica that as part of its commitment to safety a new company internal task force reviewed the studies and other data and continues its work.
After finding "no signs or symptoms of potential injury to the brain" associated with Omniscan and "no evidence of cytotoxicity (cell toxicity) in published autopsy studies" the task force concluded that "continued use of Omniscan according to approved product labeling" is appropriate, GE said.
Bayer told ProPublica patient safety is its "primary concern" and said it had reached out to the authors of the original research studies "to clarify their findings," even though "none of these studies indicate any clinical implications." The company said it was continuing to monitor the situation.
GE and Bayer have confidentially settled hundreds of lawsuits – many involving deaths – while denying liability for their contrast agents.
In 2013, one case went to trial in Cleveland and resulted in a $5 million verdict against GE. A federal appeals court upheld the verdict last year. By then the plaintiff, who had NSF, had died.
The contours of the contrast agent market have changed in recent years. Both Magnevist, once the leading agent, and Omniscan, also a top seller, have lost market share since the FDA restrictions in 2010. GE said its market share was about 10 percent last year; Bayer declined to cite a figure.
Read more reporting on drug safety by senior reporter Jeff Gerth.
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