Patients must decide whether benefits of medication outweigh the risks of potentially fatal side effects

FACED WITH a debilitating and progressive disease, would you take a drug to ease the burden even if you knew it might increase your risk of a second illness?

That’s the tough choice faced by many multiple sclerosis (MS) patients opting to take the blockbuster drug Tysabri to alleviate their symptoms. A small subset of those taking it have developed complications, and some have died.

“When faced with the probability of ending up getting worse or in a wheelchair and you have to balance out the risk, yes it’s tough,” agrees Dale Schenk, the chief scientific officer of Elan, the Irish company that invented the drug which it co-markets with its US partner Biogen.

“But you know you have the disease with certainty and you know the risk of a side effect is low – I’m not going to say what I would do, but the key is having the patient informed,” he says.

Launched in 2004, Tysabri was seen as a great white hope for those with MS, a condition affecting more than 1.3 million people globally.

An autoimmune disease where the body’s white blood cells attack themselves, the resulting diminution of the protective sheath that covers the nerves scrambles communication between the brain and the rest of the body, with symptoms including muscle spasms, stiffness, fatigue and memory and concentration problems.

Aimed at patients with highly active forms of relapsing/remitting MS or those for whom other therapies have failed, Tysabri works by blocking these errant white blood cells.

“The long and the short of it is that it keeps the white blood cells out of the brain,” explains Schenk, during a visit to Elan’s Dublin headquarters last month.

At present, about 60,000 MS patients take Tysabri. Some 124 of those, however, who are also carriers of a common virus called the JC virus, have gone on to develop a rare brain infection called progressive multifocal leukoencephalopathy or PML – 23 people have died from the complication.

Schenk explains the JC virus exists in about 50 per cent of the population but remains dormant because our immune systems keep it in check. However, some drugs that adjust the immune system, including Tysabri, appear to promote activation of JC virus in some patients, leading to PML.

An Irish woman is among those to have developed such complications from the drug. Taking Tysabri since 2006, Dr Natalie Murphy developed PML in 2009 and is in a paraplegic state in Sligo General Hospital.

“One of the theories is that for one reason or another in a small subset of patients who take Tysabri and have the JC virus, it can become activated in the brain to cause PML,” says Schenk. “We don’t understand why it’s such a small subset, but there is a correlation obviously.”

But for roughly half the population who don’t have the JC virus, there is a greatly reduced likelihood of developing PML when taking Tysabri. With a blood test for the virus now available in Europe, the decision of whether or not to begin or to continue taking the drug could become less fraught.

“The European authorities have said they feel it should be one of the three criteria used for assessing the risk to Tysabri patients,” says Schenk. How long a patient has been taking Tysabri and whether they have previously been on other heavy-duty immunosuppressant drugs are also factors in assessing the risk of PML.

“The test is not whether you should take or not, it’s just one of three criteria you use to help with the judgment,” says Schenk.

Careful not to overstate the benefits of the drug he was instrumental in inventing, he says, “The key thing is that reduces your probability of additional exacerbation . . . and we have to be accurate here and not necessarily say the treatment makes them better, but the probability of getting worse is decreased relative to placebo effects.”

For many people with MS, these benefits far outweigh the risk of developing the potentially fatal PML.

“Since the test has been out there, those who have taken it and are positive, most still stay on . . . they’ve said, ‘I understand the risk, but the therapy is still so important to me I want to take that risk’.”

Elan’s Dublin-based vice president of investor relations, David Marshall, agrees. “If they know the risk factors and they want to come off it, their choice is either, my disease will mostly likely return within six months when the Tysabri is fully out of my system, so I have a very high probability of my MS coming back and my disability increasing again and my quality of life collapsing, or I can continue taking it and have a slightly higher risk of a rare side effect. And that’s a tough decision.”

With 7,000 MS patients in Ireland, Elan says it can’t put a figure on the number of those who are taking Tysabri, though it says it has “about 10 per cent market share of all MS treatments across the world”.

MS Ireland’s information sheet on the drug quotes the risk of developing PML as one in 1,000. However, it says the risk is decreasing as neurologists and patients become more vigilant around its symptoms.

The potential risk of taking Tysabri, like many drugs for chronic diseases, is one that doctors and patients must weigh up for themselves. “We talk so much about risk,” says Schenk, “but if the probability of being disease or progression free increases with treatment, to patients that might end up being more important than the risk.”

* About 60,000 MS sufferers take Tysabri. Some 124 of those, however, who are also carriers of a common virus called the JC virus, have gone on to develop a rare brain infection called progressive multifocal leukoencephalopathy, or PML –23 people have died from the complication.