Sustained improvement revealed by post-hoc analysis
In addition to updates on the two European patients who developed PML, Biogen and Elan announced that “Tysabri demonstrates sustained improvement in functional outcomes in multiple sclerosis patient according to new post-hoc analysis.”
These findings were derived from a subset analysis of the Phase III AFFIRM trial examining sustained improvement in disability among patients. Improvement in disability was defined as a one-point decrease in EDSS score sustained for 12 weeks. In patients with a baseline EDSS score ≥ 2.0, the probability of achieving sustained improvement with natalizumab treatment was 29.6% as compared to 18.7% with placebo. In patients with an EDSS score ≥ 2.0 and highly active disease at baseline, the difference between groups was greater, 35.5% for Tysabri and 15.4% for placebo.
"While, like TYSABRI, other therapies have shown a slowing of progression in disability, this analysis represents the first evidence supporting a sustained improvement in function associated with an approved disease modifying therapy."
JC and BK virus in natalizumab-treated patients
Researchers from the MS Research Center of New York discuss the importance of identifying natalizumab-treated patients who are at greater risk of developing PML by detecting JC virus DNA and BK virus in patients prior to the actual development of PML.
The plasma and cerebrospinal fluid (CSF) of 200 natalizumab-treated patients were screened at baseline, and after 6 and 12 months of treatment, in addition to neurological evaluations and brain MRIs. After six months of treatment, seven of the 200 patients had detectable JCV/BKV DNA, while no viral DNA was detectable at baseline. Natalizumab treatment was discontinued in any patient with positive viral DNA. All seven patients converted to undetectable viral DNA within 6 months.
At 6 months the detection rate of JCV/BKV virus in CSF or plasma is 7 of 200 (3.5%) natalizumab-treated patients. Despite this finding, no cases of PML have occurred. Ongoing 12-month analysis in patients who had undetectable CSF/plasma JCV/BKV after 6 months, will allow for more definitive conclusions.
Varicella zoster meningitis in a multiple sclerosis patient after twenty doses of natalizumab
From Hope Neurology MS Center in Knoxville comes a case study of a 51-year-old man with relapsing remitting MS who received his 20th treatment of natalizumab on 4/3/08. Two days after treatment, he developed back pain, which he attributed to exertion; the next day, headache, progressive in severity and associated with myalgia and chills. He had a small area of non-blistering redness over his right biceps. His headache became severe.
A lumbar puncture performed 2 days after headache onset showed white blood cells. Varicella zoster PCRs in cerebrospinal fluid were positive. Brain magnetic resonance imaging did not show meningeal enhancement or additional lesions. Cognition was minimally affected. He was admitted and started on broad spectrum antibiotics, including 14 days of IV acyclovir (an antiviral drug) and 3 days of plasmapheresis. His headache improved on the third day of plasmapheresis. He continues to recuperate at home.
Although rarely reported, prolonged treatment with natalizumab can be associated with opportunistic and recurrent chronic infection. Vigilance in monitoring these patients is prudent.
As a proactive patient, I believe it is important to be aware of efficacy and safety issues of any medication, especially those used to treat a complicated disease such as multiple sclerosis.
What do you think? Should we be aware of the worst case scenarios, or should we simply trust that all will be well as we attempt to stay well?