Preliminary results from a new study suggest that multiple sclerosis (MS) patients who take a recommended “holiday” from the drug Tysabri (natalizumab) may have a significantly higher risk of suffering renewed disease activity within six months of halting the drug.
In fact, in the study—a randomized, controlled clinical trial of 175 patients—scientists found that more than half of the MS patients taken off Tysabri for six months either relapsed or developed new brain lesions on MRI scans. The RESTORE study’s initial results were presented as an abstract at last week’s European and Americas Committees for Treatment and Research in Multiple Sclerosis.
Experts have long suggested that MS patients who take Tysabri should take these so-called “holidays” from the drug in an attempt to reduce their risk of developing progressive multifocal leukoencephalopathy (PML). According to the National Institute of Health, PML is a disease of the white matter of the brain that is caused by an infection by a usually harmless virus known as polymavirus JC, or the JC virus. The virus targets the cells that myelin, the material that surrounds and insulates nerve cells.
Most people in the general population carry the JC virus without any problems, but for those who have a weakened immune system—either due to disease activity or because of medications used to treat chronic disease—it can be quite dangerous. The early symptoms of PML are often confused with signs of MS relapse and can include changes in mental status, motor function problems, and visual disturbances. Seizures, speech problems, and dizziness can also occur in people with PML. Severe disability or death can result from the destruction of white matter in the brain that interferes with nerve cells’ ability to function properly.
Tysabri is one of the drugs—along with such meds as corticosteroids and medicines that suppress organ rejection in transplant patients—that can cause the JC virus to reactivate and put patients at risk for PML. Because the long-term, uninterrupted use of Tysabri is a known risk factor for PML, doctors often take patients off the medication for periods of time to allow the immune system to “rebound” and thus reduce the patient’s PML risk. Previous studies have found that Tysabri users’ risk of getting PML is eight times greater in the second year of their treatment of with the drug than in the first year.
The Cleveland Clinic’s RESTORE study was designed to see what the effects of this treatment interruption might be for MS patients. In this trial, researchers either allowed patients to continue treatment with Tysabri or gave them a choice of taking interferon-beta-1a, Medrol (methylprednisolone), or Copaxone (glatiramer acetate). Others were given a placebo as a control group. All of the patients stayed on these treatments for six months.
At the end of the study period, researchers used brain MRI scans to look for renewed disease activity or for new gadolinium-enhancing lesions in the brain. Here were the preliminary results of the presence of these symptoms in the five groups:
- Placebo: 61%
- Copaxone: 60%
- Medrol: 55%
- Interfern-beta-1a: 29%
- Tysabri: 5%
The researchers stress two things about this study. First, they say the results are very preliminary, and some of the differences in the presence of disease activity could be due to heightened disease activity in patients before the study began. They say doctors should continue to practice what they call “risk stratification” – the assessment of the risks versus the benefits of prolonged use of Tysabri when the severity of the patient’s disease activity is also factored in.
The study’s lead researcher, Dr. Robert Fox, also said in an interview with MedPage Today that the results could mean frequent MRI scans during Tysabri “holidays” could help doctors find signs of renewed MS activity earlier, thus helping to them to respond more quickly before Tysabri-interruption disease relapse takes place.
The RESTORE study was funded by Biogen Idec and Elan, the makers and marketers of Tysabri.
The original abstract can be found here: http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=139558&XNSPRACHE_ID=2&XNKONGRESS_ID=150&XNMASKEN_ID=900
Other sources: MedPage Today; National Institutes of Health; UptoDate.com; Tysabri.com; National MS Society.
Published On: October 31, 2011