In a new safety manual on the use of MRI contrast agents, which are injected prior to an MRI to improve the results of imaging scans, the American College of Radiology (ACR) identified the three products as those most frequently associated with the rare and often fatal condition that is associated with the hardening and thickening of the skin, which severely restricts movement. ACR said that investigators now believe that the “intrinsic properties” of those three products increases the likelihood of at-risk patients developing NSF.

The most cases by far were associated with GE Healthcare’s Omniscan MRI Contrast, which was linked to at least 382 cases of NSF out of approximately 13 million doses. By comparison, the second highest number of cases was associated with Bayer’s Magnevist MRI contast, which had 195 cases of NSF out of approximately 23 million doses. The third highest was OptiMARK MRI contrast by Covidien, which was linked to 35 cases of NSF out of 4.7 million doses.

ACR noted that the difference in rates between those three and other gadolinium-based contrasting agents could be due to both toxicity and market share.

NSF, which is sometimes referred to as nephrogenic fibrosing dermopathy (NFD), is a rare condition that is only known to occur after exposure to a gadolinium-based contrast agent (GBCA) among individuals with impaired kidney function. There is no cure for the painful and debilitating condition, and in many cases it results in death over time.

The manufacturers of all types of gadolinium-based agents were required by the FDA to add the same “black box” warning about the risk of NSF from MRI with contrast in the United States in 2007, indicating that individuals with severe kidney problems could develop NSF. However, many have argued that the warnings about Omniscan side effects should be stronger than those on other available contrast agents, possibly calling for a ban on use of the product in some patients.

Hundreds of nephrogenic systemic fibrosis lawsuits have been filed in the United States by individuals who developed the condition after receiving a gadolinium-based contrast agent. Out of the five approved contrast agents, Omniscan has been associated with the most lawsuits over NSF, outnumbering the other drugs in proportions that far exceed their market share. It has been estimated that about 75% of all NSF lawsuits involve cases where the plaintiff developed the condition after use of Omniscan, even though GE’s contrast agent only accounts for about 30% of the market share.

In its 2009 annual report, the company states that it has been served with approximately 310 nephrogenic systemic fibrosis lawsuits involving Magnevist, and settlements have been reached with approximately 140 of the plaintiffs. While Bayer indicates that it is not admitting liability in the cases, additional lawsuits are anticipated and the company will continue to consider the option of nephrogenic system fibrosis settlements on a case-by-case basis.

The cases involve allegations that Bayer was aware that side effects of gadolinium contrast agents like Magnevist could result in the debilitating condition for some users and failed to adequately warn users and the medical community about the risk of NSF.

Magnevist is one of five gadolinium based contrast agents manufactured by four different company. Other manufacturers have been named in the same or similar lawsuits over nephrogenic systemic fibrosis, with GE Healthcare’s Omniscan contrast agent associated with the most cases in the United States. Unlike Bayer, GE Healthcare has not indicated an intention to settle Omniscan cases.

Nephrogenic systemic fibrosis (NSF), which is sometimes referred to as nephrogenic fibrosing dermopathy (NFD), is only known to occur after exposure to a gadolinium-based contrast agent (GBCA) among individuals with impaired kidney function. The painful and disfiguring condition causes a hardening and thickening of the skin and other tissue throughout the body, severely restricting movement. There is no cure for the progressive disorder, and no consistently successful treatments are available.

The FDA ordered the manufacturers of all types of gadolinium MRI contrast agents to add a “black box” warning in 2007, indicating that individuals with severe kidney problems could develop NSF. In December, an FDA advisory panel of medical experts met to review the risk of NSF, and recommended that the warnings for Bayer’s Magnevist and GE’s Omniscan should be strengthened to indicate that they should not be used by patients with moderate to severe kidney problems. Although the FDA is not bound to follow the recommendations of their advisory panel, they usually do.

Although all types of gadolinium MRI contrast agents have been linked to NSF, reports suggest that the risk of NSF associated with Omniscan may be higher than other contrast agents. Many experts have argued that the warnings about the risk of NSF from Omniscan should be stronger than what is contained on the other contrast agents.

All federal gadolinium lawsuits have been consolidated in the U.S. District Court for the Northern District of Ohio as part of a multidistrict litigation (MDL), for pretrial litigation. The lawsuits target Bayer and GE, as well as Bracco Diagnostics’ MultiHance and ProHance, and Mallinckrodt’s OptiMARK.

Neither party disclosed details of the settlement, but both GE Healthcare and Henrik Thomsen, Professor of Radiology at Herley Hospital in Copenhagen, made conciliatory statements last week. Thomsen has been an outspoken crusader against Omniscan, speaking at medical conferences and writing several papers about the risk of problems from the gadolinium MRI contrast agent, which is used to improve scan results.

Thomsen sounded the warning bell about potential risks with Omniscan after noticed that 20 of his patients were suffering from NSF, which causes a hardening and thickening of the skin and other tissue throughout the body, severely restricting movement. Sometimes referred to as nephrogenic fibrosing dermopathy (NFD), the rare condition is only known to occur after exposure to a gadolinium-based contrast agent (GBCA) among individuals with impaired kidney function. There is no cure for the painful and debilitating disorder, and in many cases it results in death.

GE hit Thomsen with a libel suit in British courts, and Thomsen responded with a counterclaim, saying that the company was trying to gag scientific debate over the issue. Now, both say that their reactions were due to a misunderstanding, according to a press release by GE Healthcare.

“My purpose was to share with fellow clinicians and healthcare professionals my experience in managing a serious problem at our hospital where we found 20 patients suffering from NSF. The cause was unknown, but in early 2006, it was clear to us that all of our nephrology patients with NSF had only one factor in common; they had all been exposed to Omniscan,” Thomsen said. “It was not my intention to suggest on the basis of the evidence then available to me that GE Healthcare had marketed Omniscan knowing that it might cause NSF.”

GE officials also said their actions were misunderstood.

“It was not the intention of GE Healthcare by bringing proceedings for libel against Professor Thomsen to stifle academic debate,” said Dr. Lynne Gailey, executive vice-president of GE Healthcare communications. “GE Healthcare objected to statements made by Professor Thomsen which it interpreted as suggesting that it had known from the outset that Omniscan caused NSF. GE Healthcare accepts, however, that Professor Thomsen’s concerns were expressed in good faith. GE Healthcare regrets that these proceedings were necessary to reach the common understanding described in this statement.”

Although all types of gadolinium MRI contrast agents have been linked to nephrogenic systemic fibrosis, multiple reports have suggested that the risk of NSF associated with Omniscan may be higher than other contrast agents.

In 2007, the manufacturers of all types of gadolinium-based agents in the United States were required by the FDA to add a “black box” warning to their products, indicating that individuals with severe kidney problems could develop NSF. However, many have argued that the warnings about the risk of NSF from Omniscan should be stronger, possibly calling for a ban on use of the product in some patients.

Approximately 350 nephrogenic systemic fibrosis lawsuits have been filed in the United States by individuals who developed the condition after receiving a gadolinium-based contrast agent. Out of the five approved contrast agents, Omniscan has been associated with the most cases of NSF, outnumbering the other drugs in proportions that far exceed their market share. It has been estimated that about 75% of all NSF lawsuits involve cases where the plaintiff developed the condition after use of Omniscan, even though GE’s contrast agent only accounts for about 30% of the market share.

Henrick Thomsen, a leading medical scientist and radiologist, has been an outspoken crusader against Omniscan, speaking at medical conferences and writing several papers about the risk of problems from the gadolinium-based contrast agent, which is used to improve magnetic resonance imaging (MRI) scan results.

Thomsen sounded the warning bell about potential risks with Omniscan after noticed that 20 of his patients were suffering from nephrogenic systemic fibrosis, which causes a hardening and thickening of the skin and other tissue throughout the body, severely restricting movement.

GE Healthcare attempted to silence Thomsen through use of British libel laws, but The Guardian reports that the Danish radiologist will file a counterclaim for libel in the ongoing battle

Although all types of gadiolinium MRI contrast agents have been linked to nephrogenic systemic fibrosis, multiple reports have suggested that the risk of NSF is increased with Omniscan.

Nephrogenic systemic fibrosis (NSF), which is sometimes referred to as nephrogenic fibrosing dermopathy (NFD), is a rare condition that is only known to occur after exposure to a gadolinium-based contrast agent (GBCA) among individuals with impaired kidney function. There is no cure for the painful and debilitating disorder, and in many cases it results in death.

The manufacturers of all types of gadolinium-based agents were required by the FDA to add the same “black box” warning in the United States in 2007, indicating that individuals with severe kidney problems could develop NSF. However, many have argued that the warnings about Omniscan side effects should be stronger than those on other available contrast agents, possibly calling for a ban on use of the product in some patients.

Approximately 350 nephrogenic systemic fibrosis lawsuits have been filed in the United States by individuals who developed the condition after receiving a gadolinium-based contrast agent. Out of the five approved contrast agents, Omniscan has been associated with the most cases of NSF, outnumbering the other drugs in proportions that far exceed their market share. It has been estimated that about 75% of all NSF lawsuits involve cases where the plaintiff developed the condition after use of Omniscan, even though GE’s contrast agent only accounts for about 30% of the market share.

The NSF lawsuit was filed by Peter Gerber against Bayer Healthcare Pharmaceuticals, over problems caused by exposure to their Magnevist MRI contrast agent.  On Monday, a trial date was scheduled for January in the San Francisco Superior Court before Judge Curtis Karnow.

Unless a settlement is reached before the trial, the case is expected to be the first submitted to a jury out of hundreds of other similar cases that have been filed in state and federal courts throughout the United States against Bayer and the makers of other gadolinium-based contrast agents.  Many of the nephrogenic systemic fibrosis lawsuits against against Bayer have already settled, with most of the remaining cases pending against GE Healthcare over problems caused by their Omniscan MRI contrast agent.

Nephrogenic systemic fibrosis (NSF), which is sometimes referred to as nephrogenic fibrosing dermopathy (NFD), is a rare condition that is only known to occur after exposure to a gadolinium-based contrast agent (GBCA) among individuals with impaired kidney function.  The painful and disfiguring condition causes a hardening and thickening of the skin and other tissue throughout the body, severely restricting movement.  There is no cure for the progressive disorder, and no consistently successful treatments are available.

The FDA ordered the manufacturers of all types of gadolinium MRI contrast agents to add a “black box” warning in 2007, indicating that individuals with severe kidney problems could develop NSF.  This week, an FDA advisory panel of medical experts met to review the risk of NSF, and recommended that the warnings for Bayer’s Magnevist and GE’s Omniscan should be strengthened to indicate that they should not be used by patients with moderate to severe kidney problems.  Although the FDA is not bound to follow the recommendations of their advisory panel, they usually do.

In addition to the Gerber NSF lawsuit and other cases filed in state courts, there are about 350 cases consolidated for pretrial litigation in federal court in the Northern District of Ohio as part of a multidistrict litigation (MDL).  The first trial in the MDL is expected to begin next year.

Covidien PLC announced the label change on Monday, just a few weeks before an FDA advisory committee is scheduled to re-examine the risk of gadolinium side effects, and the “black box” warning that was placed on all MRI contrast agents in 2007. The FDA scheduled the meeting in response to mounting criticism that called for a stronger NSF warning for Omniscan, a different gadolinium-based contrast agent manufactured by GE Healthcare.

Gadolinium-based contrasting agents (GBCAs) are often given to patients undergoing magnetic resonance imaging scans (MRIs) to improve the outcome of the scans, allowing doctors to distinguish blood vessels from nearby tissue. Gadolinium contrast agents were prescribed to more than 9.5 million patients in the United States in 2008.

For a small sub-set of the population with moderate to severe kidney problems, side effects of the MRI contrast agents have been linked to an increased risk of nephrogenic systemic fibrosis (NSF), which is also sometimes referred to as nephrogenic fibrosing dermopathy (NFD). The rare progressive disorder is associated with scarring of the skin and connective tissue, which can cause the skin to become thick, hard, rigid and coarse, severely restricting movement of the joints. It also results in scarring or fibrosis of other organs, and in many cases it is fatal.

In May 2007, the FDA required the makers of all five types of gadolinium MRI contrast available at that time to add a “black box” warning about the risk of NSF among individuals with kidney problems. Although a boxed warning is the strongest that can be placed on a prescription medication, critics have argued that the NSF warning for GE’s Omniscan should be worded stronger than the others, specifically indicating that it should not be used by those with severe kidney failure, as opposed to only cautioning doctors about the risk of NSF.

The vast majority of cases of nephrogenic systemic fibrosis identified in the United States have been associated with the use of GE’s Omniscan, although it only accounts for about 30% of the market share.

In a statement issued Monday, Covidien PLC, which manufacturers the competing Optimark contrast agent, announced that they are voluntarily contraindicating use of their gadolinium-based product in MRI procedures involving patients with severe renal impairment. They have submitted proposed label changes to the FDA, indicating that the drug should not be used in “patients with acute or chronic severe renal insufficiency (glomerular filtration rate of less than 30 mL/min /1.73m2) or acute renal insufficiency of any severity due to hepato-renal syndrome or in the perioperative liver transplant period.” The new label will go into effect immediately and apply in every country where Covidien sells the drug.

GE Healthcare has resisted calls to place a similar contraindication on their Omniscan contrast agent, despite indications that the risk of NSF/NFD is greater with their product.

There are currently about 400 nephrogenic systemic fibrosis lawsuits filed in state and federal courts throughout the United States against the makers of MRI contrast agents, including GE Healthcare (Omniscan), Bayer Healthcare (Magnevist), Bracco Diagnostics (MultiHance and ProHance) and Covidien (Optimark). The NSF lawsuits all allege that the manufacturers did not adequately research their product and failed to warn consumers about the risk of developing the debilitating and life-threatening condition.

It has been estimated that about 75% of all NSF lawsuits involve plaintiffs who developed the condition after use of Omniscan, according to a report by ProPublica, far exceeding their market share for gadolinium MRI contrast agents.

An FDA advisory committee is scheduled to re-examine the NSF warnings for gadolinium-based contrast agents at a meeting scheduled for December 8, 2009.

The FDA ordered the manufacturers of all gadolinium MRI contrast agents to add a “black box” warning in 2007, indicating that individuals with severe kidney problems could develop the rare disorder, also sometimes referred to as nephrogenic fibrosing dermopathy (NFD), which causes widespread areas of tight, thick and rigid skin that severely restricts movements. It can also result in scarring to internal organs and ultimately may be fatal.

A joint meeting of the Cardiovascular and Renal Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee has been scheduled for December 8. The two committees will review the FDA’s decision to provide the same warning to healthcare professionals and patients.

Out of the five approved gadolinium contract agents, Omniscan has been associated with the most cases of NSF, outnumbering the other drugs in proportions that far exceed their market share. Although GE’s contrast agent only accounts for about 30% of the market, it has been estimated that about 75% of all NSF lawsuits involve cases where the plaintiff developed the condition after use of Omniscan, according to a report by ProPublica.

The FDA’s decision to require the same black box warning for all MRI drugs that use the metal gadolinium went against the advice of two of its own staff doctors. The two FDA doctors each recommended more attention be placed on Omniscan, and that it possibly be banned for use in some patients.

At the meeting in December, the advisory committee will revisit the decision to treat all of the contrast agents the same and determine whether any changes are necessary.

The cases have been filed against Bayer by individuals with pre-existing kidney issues who developed a rare condition known as Nephrogenic Systemic Fibrosis (NSF), which is associated with the progressive hardening and thickening of the skin and other tissues throughout the body.

About 400 gadolinium lawsuits have been filed in state or federal courts against Bayer and the makers of four other similar types of MRI contrast agents, including GE Healthcare’s Omniscan, Bracco Diagnostics’ MultiHance and ProHance, and Mallinckrodt’s OptiMARK.

The NSF lawsuits all allege that the manufacturers did not conduct adequate testing for their products and failed to warn consumers about the risk of developing the debilitating and potentially life-threatening disease.

Most of the lawsuits filed have involved the use of GE Healthcare’s Omniscan contrast agent. However, Bayer’s Magnevist has been identified as the contrast agent used in over 60 of the Nephrogenic Systemic Fibrosis lawsuits filed so far in federal court.

Although details of any gadolinium settlement negotiations have not been publicly released, during a recent status conference held on March 6, 2009, Judge Polster confirmed that discussions have taken place and suggested that several cases may settle in the near future.

The federal gadolinium litigation has been consolidated before Judge Polster in the United States District Court for the Northern District of Ohio for purposes of pretrial litigation. The Court has pushed for an aggressive trial schedule since many of the plaintiffs are very ill and may not survive lengthy litigation, which has put pressure on the manufacturers.

The parties have each selected 10 cases, known as Eligible Trial Pool Cases, which are currently undergoing early discovery in preparation for the first trials that are expected to begin next year.

Judge Polster has agreed to allow the parties to substitute any current Eligible Trial Pool Case that settles before April 6, 2009 with another lawsuit.

The final list of 20 cases will later be narrowed down to 10, with 5 chosen by the plaintiffs and 5 chosen by the defendants for the first trials. The parties will then attempt to agree on the first four which will be scheduled for trial, with two from each side’s list.