Friday, March 09, 2007

Multiple sclerosis drug brings lethal risks, but great promise for some

By John Fauber

Milwaukee Journal Sentinel

MILWAUKEE - Eric Schmitt munches on a roast beef sandwich as an IV hooked up to his arm drips a precious but potentially lethal fluid into his vein.

Schmitt, 35, knows there is a slight chance the new drug might kill him, but without it his multiple sclerosis could flare up, bringing back the lack of feeling in his lower body, vision problems and difficulty walking.

"I didn't have much choice," he says.

Krista Chapman wakes up worried at 3 a.m. on the day of her first treatment.

After a horrible year of MS relapses in 2006, she reckons that the same drug, Tysabri, will reduce the odds of another setback from which she might not recover, sparing her from disorienting vertigo and overpowering fatigue.

But it also could cause a fatal viral infection in her brain. And at 37, she is too young to die, even though the odds of that seem slim.

As the drug, which costs several thousand dollars a month, slowly is infused into the back of her hand, she seems relaxed sitting up in her hospital bed.

For Schmitt and Chapman as well as an untold number of other MS patients, Tysabri has created a dilemma found with few other medications that treat disabling, but rarely fatal, diseases such as MS.

The drug was taken off the market in 2005 after three people out of about 2,900 who had been in clinical trials developed brain infections. Two of them died. There is no treatment for the infection, known as progressive multifocal leukoencephalopathy, or PML. And there is no way of knowing who will get it.

The risk of the complication initially was calculated to be about one in 1,000, but doctors say that is an estimate and no one knows the true risk.

In addition, because Tysabri works by blocking the ability of certain immune cells to get into the brain, it may make patients more susceptible to opportunistic infections in other parts of the body.

The drug was allowed back on the market in July with restrictions and a black box warning, the most serious alert that can be placed on a drug label.

The angst over the infection, in part, has been assuaged by Tysabri's huge promise. There is some indication that it may be twice as effective as other MS drugs and that it can reduce the number of relapses by two-thirds.

"If it wasn't for the (brain infection risk), everybody would be taking it because it is such a powerful drug," said Bhupendra Khatri, a neurologist and medical director of the Regional MS Center at Aurora St. Luke's Medical Center in Milwaukee. "You need to be very selective about who you treat."

Beyond the grim calculus of risk and reward, MS patients may have to factor in another troubling variable: the staggering cost of Tysabri.

The drug has a wholesale price of $2,184 for each vial used for the standard, hourlong monthly infusion session.

At least one infusion site, St. Luke's Medical Center, is billing nearly $10,000 for each monthly treatment.

Potentially, Tysabri patients could be on the drug for years, maybe the rest of their lives, possibly straining the lifetime policy limits of their insurance.

At the two other sites approved for dispensing Tysabri, the price is substantially less. Waukesha Memorial Hospital charges $2,900 for a monthly infusion. University of Wisconsin Hospital and Clinics in Madison bills $4,300. Under Medicaid, Wisconsin pays pharmacies about $2,400 for the drug.

All of those charges may be subject to rebates or discounts, depending on who is paying the bill.

For instance, a claim receipt from one Tysabri patient shows St. Luke's billed Humana Insurance $9,991, minus $3,996 for a plan discount, resulting in a net payment of $5,995. St. Luke's declined to comment on pricing.

A spokeswoman for the drug's maker said the company has no control over how much clinics charge for administering Tysabri. Patient ranks growing

Nationally, about 5,000 patients are taking the drug and another 3,000 are waiting to begin treatment, said Amy Brockelman, a spokeswoman for Biogen Idec, which markets Tysabri along with Elan Pharmaceuticals.

"We believe Tysabri has the potential to eclipse all the other MS therapies over time," she said.

MS is an autoimmune disease that usually is diagnosed in people between the ages of 20 and 50. About 400,000 Americans have the disease; women get the disease about twice as often as men.

In MS, certain immune cells enter the brain or spinal cord and mistakenly cause inflammation that damages myelin, the protective coating on the roots of brain cells. As the myelin becomes damaged, communication between brain cells is disrupted and some cells die, resulting in any of a variety of problems such as difficulty controlling movement, blurred vision and cognitive deficits.

Tysabri prevents the immune cells from getting into the brain. It binds to the surface of the cells and inhibits their movement from the bloodstream to the brain.

This helps prevent the autoimmune attack on the brain, but it also makes the brain more susceptible to a common pathogen known as the JC virus. It is the JC virus that causes the brain infection.

Tysabri essentially turns the brain into a gated community, said John Fleming, a professor of neurology and director of the University of Wisconsin's MS clinic.

"It keeps out all the criminals," Fleming said. "Unfortunately, it also keeps the cops out."

The problem in assessing the risk of Tysabri is that it has been tested for only about two years, he said. No one knows if the brain infection risk grows or diminishes five years out or longer, he said.

"If it turns out to be safe, it could be the predominant treatment for MS," Fleming said. "If there are more cases of (brain infection), it wouldn't surprise me if the FDA took it off the market."

For the moment, Tysabri patients such as Schmitt and Chapman may get some reassurance knowing that all three of the people who developed the brain infection had been on other immune-modulating drugs as well as Tysabri, and that may have contributed to their brain infections. Under the new restrictions that allowed Tysabri back on the market, it must be administered alone.

Schmitt, who was diagnosed with MS in 1998, has been part of a clinical trial to further establish the safety of Tysabri. He got his last infusion last month as part of the trial at St. Luke's. Since he went back on the drug last year, feeling has returned to the lower part of his body and he has never felt better, he said.

For Schmitt, a pharmacist who is married and has a 2-year-old child, his worries about the drug had to be set aside.

"I'm either disabled or still working," he said. "I'm 35. I've got to keep working."

Chapman began considering Tysabri after she was hospitalized because of three separate relapses in 2006. During those setbacks, she had severe vertigo, trouble speaking and swallowing, difficulty seeing and loss of feeling from the waist down.

She still has a great deal of fatigue and, at times, she gets around with a cane, walker or scooter.

"There are days when there is so much fatigue that I can't get out of bed," she said.

Chapman had been on a daily injectable MS drug, but it was losing its effectiveness, she said. She stopped another drug because it caused depression.

"All the neurologists said, 'You have to do something soon,'" she said. "It (going on Tysabri) was frightening. I knew the risk."

Her doctor, neurologist Stanya Smith, said for some patients the drug may be the only way to avoid disabling relapses.

"I have to be convinced in my heart as a physician that it's the only option I have left," said Smith, who manages the MS clinic at Waukesha Memorial.

For Chapman, the final decision was made over Thanksgiving weekend.

About 10 family members, including her husband, Jim, her parents and siblings, gathered at her mother-in-law's home. They each got a vote on whether she should go on Tysabri.

She got her first infusion at Waukesha Memorial last month.