It is clear that the derisking of PML is working. When you pick-up PML in the asymptomatic phase PMLers do better. The real question is that with so many other options, and emerging treatment option, both on- and off-label, should we putting anyone at risk of developing PML unnecessarily? I would say no, but then I don’t have rapidly evolving severe MS and I have not had my life transformed by natalizumab.
Therefore wouldn’t be nice if we could develop and anti-viral drug that could clear the JC virus from your body? A viral cure is not science fiction this has been done with other viruses, a good example are the new protease inhinitors for hepatitis C. I have recently become aware that teriflunomide (Aubagio) is a pretty potent antiviral with clinically effecitve activity against the BK virus, a cousin of JCV. Teriflunomide may be just the agent we are looking for. We have put forward a tentative proposal to test teriflunomide againts JCV. Let’s hope 2017 bring forth a flurry of research activity to tackle the PML problem. PML is a biological problem and if we put our minds and efforts towards solving it we can solve it; most, if not all, biological problems in the long-term prove to be tractable.
Prosperini et al. Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry. PLoS One. 2016 ;11(12):e0168376. doi: 10.1371/journal.pone.0168376.
BACKGROUND: The monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV).
OBJECTIVE: To describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions.
METHODS: An Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated.
RESULTS: Ten patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01).
CONCLUSION: Our findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival rate, and confirm the utility of MRI as a surveillance tool for NTZ-treated patients.