The earlier the smaller the better for natalizumab-associated PML: in MRI vigilance veritas ?
PHAN BA, Remy ; Belachew, Shibeshih ; et al
in Neurology (2012), 79
Natalizumab-associated progressive multifocal leukoencephalopathy (N-PML) in multiple sclerosis (MS) is due to CNS infection by the opportunistic JC virus (JCV). As of december 2011, 193 confirmed cases ... [more ▼]
Natalizumab-associated progressive multifocal leukoencephalopathy (N-PML) in multiple sclerosis (MS) is due to CNS infection by the opportunistic JC virus (JCV). As of december 2011, 193 confirmed cases of N-PML have been observed, giving rise to an overall risk of approximately 0,202%. N-PML pathogenesis remains partially elusive although risk factors have now been clearly delineated. In patients with prior JCV infection detected by serum anti-JCV antibodies, duration of therapy and prior use of immunosuppressants (IS) increase the risk of N-PML. The clinical outcome of MS patients who developed N-PML was highly variable, ranging from asymptomatic case to varying degrees of neurological disability or even death. It was also observed in real life setting that the earlier N-PML was diagnosed and treated, the better was the clinical outcome. Clinical vigilance is now considered as the established cornerstone of PML risk-management algorithm. Here we present early MRI features of 4 out of 8 N-PML cases, which were observed in Wallonia-Brussels and Northern France in more than 4 years of post-marketing utilization of natalizumab for both regions. We are not aware of the specific context and outcome of the 4 other N-PML cases, which were diagnosed and treated in other centers. The reported cases emphasize that (i) N-PML can have a long presymptomatic course while still being clearly detectable with MR imaging, (ii) N-PML can have a benign outcome provided it is diagnosed and treated early, (iii) a clinically symptomatic N-PML may be a further advanced infection with a poorer prognosis, and (iv) periodic brain MR scans, particularly in high risk situations, are likely to provide earlier detection of N-PML and better outcomes. [less ▲]Detailed reference viewed: 99 (16 ULg)
Natalizumab induces a rapid improvement of disability status and ambulation after failure of previous therapy in relapsing-remitting multiple sclerosis.
Belachew, Shibeshih ; Phan-Ba, Rémy ; et al
in European Journal of Neurology (2010), 18(2), 240-245
Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy ... [more ▼]
Background: Natalizumab (Tysabri) is a monoclonal antibody that was recently approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Our primary objective was to analyse the efficacy of natalizumab on disability status and ambulation after switching patients with RRMS from other disease-modifying treatments (DMTs). Methods: A retrospective, observational study was carried out. All patients (n = 45) initiated natalizumab after experiencing at least 1 relapse in the previous year under interferon-beta (IFNB) or glatiramer acetate (GA) treatments. The patients also had at least 1 gadolinium-enhancing (Gd+) lesion on their baseline brain MRI. Expanded Disability Status Scale (EDSS) scores, and performance on the Timed 25-Foot Walk Test and on the Timed 100-Metre Walk Test were prospectively collected every 4 weeks during 44 weeks of natalizumab treatment. Brain MRI scans were performed after 20 and 44 weeks of treatment. Results: Sixty-two per cent of patients showed no clinical and no radiological signs of disease activity, and 29% showed a rapid and confirmed EDSS improvement over 44 weeks of natalizumab therapy. Patients with improvement on the EDSS showed similar levels of baseline EDSS and active T1 lesions, but had a significantly higher number of relapses, and 92% of them had experienced relapse-mediated sustained EDSS worsening in the previous year. A clinically meaningful improvement in ambulation speed was observed in approximately 30% of patients. Conclusions: These results indicate that natalizumab silences disease activity and rapidly improves disability status and walking performance, possibly through delayed relapse recovery in patients with RRMS who had shown a high level of disease activity under other DMTs. [less ▲]Detailed reference viewed: 172 (37 ULg)