Weighing the Options for MS Treatment

Jennifer Helbing, 41, of Dallas, Ga., is a busy mother of two and a full-time bookkeeper at a local elementary school. She has always had a very active lifestyle, from her high school days running on the track team to playing a tough game of tennis with her friends and now shuttling her kids to and from practice and cheering them on. Looking at her, you wouldn’t know she has MS. Helbing says that’s because she doesn’t yet have difficulty walking – one of the tell-tale signs of the disease.

Since being diagnosed in 2001, daily or weekly injections of beta interferons or Copaxone – first- line therapies for MS – have kept the disease at bay. But last year, a magnetic resonance imaging scan of her brain revealed new lesions – signs that the disease had become active and was causing damage. Helbing found herself at a crossroads. She and her care team at the Andrew C. Carlos MS Institute at Shepherd Center had to rethink her options for treatment. A monoclonal antibody called natalizumab (marketed as Tysabri^®), was at the top of the list, but Helbing had some trepidation having seen news reports about its risks.

“Tysabri^® is probably the most effective treatment we have in our toolbox to help stop MS from progressing, but it’s not without some serious safety concerns,” says Helbing’s physician, Ben Thrower, M.D., medical director of the MS Institute at Shepherd.

Jennifer Helbing of Dallas, Ga., is prepped for an IV treatment for multiple sclerosis at Shepherd Center’s MS Institute. Photo by Gary Meek

For a subset of patients with relapsing or uncontrolled MS, treatment with Tysabri^® is riskier because of the increased risk for a rare and sometimes-fatal disease called progressive multifocal leukoencephalopathy, or PML. PML is caused by the JC virus (polyomavirus JC), which is usually contracted during childhood. The virus is thought to lay dormant in the body, and typically does not cause any health problems except in individuals with seriously compromised immune systems.

Until recently, there was no way to determine which individuals were actually virus carriers. Earlier research suggested up to 90 percent of adults
may carry the virus, Dr. Thrower notes. Therefore, he and other clinicians were working under the assumption that most patients with MS would be at heightened risk for PML if given a trial of Tysabri^®.

But new data, including initial results from the ongoing, longitudinal STRATIFY clinical trial under way at Shepherd Center and 326 other sites, finds that only half of the population has detectable levels of the JC virus, meaning that Tysabri^® may be a viable option for many more patients with MS than originally thought. The blood test to detect JC virus was approved for commercial use in August of 2011 due, in large part, to its use in the STRATIFY study.
“The ability to separate out individuals who do or don’t carry the JC virus is a big leap forward
in helping us to determine who might be a safer candidate for the most effective drug we’ve got,” Dr. Thrower says.

So far, it appears the incidence of PML in Tysabri^®-treated, anti-JC virus antibody-negative patients is significantly lower than in those who test positive for the virus. Of patients with MS who are taking Tysabri^® and have contracted PML, 21 percent have died, and the remaining 79 percent are living with severe and permanent disability. Some are faring better than others.

“PML is very serious so we do everything to avoid it, and, thus far, we haven’t had a case
at Shepherd Center,” Dr. Thrower says. “Most centers will still start with the first-line injectable therapies, but when a patient doesn’t have adequate control of MS, or if they are having troublesome side effects to these medications,

Tysabri^® should be considered.”
The drug works very much like a lock and key.

By binding to receptors on the surface of white blood cells, it shuts the “door” to any white blood cells trying to make their way into the central nervous system through the blood-brain barrier.

Helbing says the decision to try Tysabri^® is likely the best she has made related to her MS.

“Every time you start a new drug, it’s scary,” she explains. “You don’t know how your body is going to respond. I felt so much more confident once I knew they would be monitoring me for the JC virus, and if, at anytime, I tested positive, I’d, of course, come off the medication.”

So far, the news has been favorable for Helbing, and because the treatment is administered as a once- monthly injection at Shepherd Center, it has been a bit of a game-changer. She no longer has to think about, prepare and give herself daily injections, which she says were nagging reminders of her disease.

“It’s convenient, and it fits my lifestyle,” Helbing says. “I’m always running around with my kids, and I don’t want to give up that time. Now, I go in once a month, and the nurses in the infusion clinic – I love them – they take care of me, and that’s my day to focus on me and my health.”

The STRATIFY study will continue to follow enrolled patients for four years to collect more data and determine conversion rates – what percentage of patients actually go from being JC virus antibody- negative to positive over time. All patients who are on or considering Tysabri^® should now receive repeat testing for the JC virus as part of their usual care.

“JC antibody testing should be part of an ongoing process to better customize therapies to the individual, rather than having to look at blanket risk,” Dr. Thrower says. “We can now counsel patients more effectively about the risks of this medication.”

Risk Factors for PML

Patients with multiple sclerosis or Crohn’s disease who are taking Tysabri^® face an increased risk for PML if they:

• Test positive for the JC virus antibody

• Have been treated with Tysabri^® for longer than two years

• Received previous treatment with immunosuppressant drugs, such as methotrexate or cyclophosphamide

The Food and Drug Administration estimates that patients with all three risk factors face about a 1 percent risk for PML (11 cases per 1,000 patients treated).