Predictors of severity and functional outcome in natalizumab-associated progressive multifocal leukoencephalopathy

Hoepner, Robert; Kolb, Eva; Dahlhaus, Stefanie; Hellwig, Kerstin; Adams, Ortwin; Kleiter, Ingo; Salmen, Anke; Schneider, Ruth; Lukas, Carsten; Chan, Andrew; Berger, Joseph R.; Gold, Ralf

doi:10.1177/1352458516667241

Cited by 25 publications

(17 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistently with previous observations, NTZ-related PML evolves in a timeframe from 6 to 12 months, with the peak of disability at 6 months and a variable degree of recovery at 12 months from the diagnosis [14,17,18,37,38]. Accordingly, we observed all deaths around 6 months from PML diagnosis [14,18].…”

Section: Discussionsupporting

confidence: 92%

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

et al. 2016

View full text Add to dashboard Cite

BackgroundThe 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).ObjectiveTo 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.MethodsAn 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.ResultsTen 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).ConclusionOur 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.

show abstract

Section: Discussionsupporting

confidence: 92%

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Important is the monitoring of immunesuppressive medication and the associated disease progressive multifocal leukoencephalopathy (PML). 42,[99][100][101][102][103] Among MS treatments, the incidence of PML is greatest with natalizumab, but there have been cases reported with newer oral medications, such as dimethyl fumarate and fingolimod. Obtaining regular MRIs for patients on these types of treatments is crucial as it may be possible to detect PML on imaging prior to fulminant clinical symptoms.…”

Section: Mri In the Monitoring Of Adverse Effects Associated With Trementioning

confidence: 99%

MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

Kaunzner

Gauthier

2017

Ther Adv Neurol Disord

113

View full text Add to dashboard Cite

Magnetic resonance imaging (MRI) has developed into the most important tool for the diagnosis and monitoring of multiple sclerosis (MS). Its high sensitivity for the evaluation of inflammatory and neurodegenerative processes in the brain and spinal cord has made it the most commonly used technique for the evaluation of patients with MS. Moreover, MRI has become a powerful tool for treatment monitoring, safety assessment as well as for the prognostication of disease progression. Clinically, the use of MRI has increased in the past couple decades as a result of improved technology and increased availability that now extends well beyond academic centers. Consequently, there are numerous studies supporting the role of MRI in the management of patients with MS. The aim of this review is to summarize the latest insights into the utility of MRI in MS.

show abstract

“…Worse functional outcome from PML was associated with higher age, higher initial JCV copy number in cerebrospinal fluid and more extensive PML disease on MRI. 17 …”

Section: Progressive Multifocal Leukoencephalopathymentioning

confidence: 99%

The role of natalizumab in the treatment of multiple sclerosis: benefits and risks

2017

Ther Adv Neurol Disord

View full text Add to dashboard Cite

Natalizumab, a monoclonal antibody that blocks lymphocyte infiltration in the central nervous system, is a valuable tool in the treatment of relapsing forms of multiple sclerosis (MS). In a phase III clinical trial comparing natalizumab with placebo over 2 years, natalizumab reduced annualized relapse rate by 68%, 12-week confirmed disability progression by 42%, and reduced contrast-enhancing lesions by 92%. In post hoc analyses, natalizumab treatment was associated with 37% of patients achieving no evidence of disease activity (versus 7% on placebo) and 30% achieving sustained disability improvement (versus 19% on placebo). Natalizumab did not achieve a statistically significant primary composite disability outcome in a trial of 887 patients with secondary progressive MS, but it did demonstrate a benefit on a prespecified component of the 9-Hole Peg Test. The greatest risk of natalizumab treatment is progressive multifocal leukoencephalopathy (PML), with a 23% mortality rate. Risk stratification on the basis of immunosuppressant exposure, natalizumab treatment duration and anti-John Cunningham virus (JCV) antibody status and index has greatly improved clinical decision making. Other potential serious natalizumab-associated risks reported in clinical trials and postmarketing settings include infusion reactions, hepatotoxicity and rare, serious opportunistic infections. With more than a decade of continuous postmarketing experience, natalizumab remains a very effective option for patients with relapsing forms of MS. To optimize appropriate selection of natalizumab for patients with relapsing MS, however, a thorough understanding of individual patient risk factors for PML or other adverse events is also required.

show abstract

Predictors of severity and functional outcome in natalizumab-associated progressive multifocal leukoencephalopathy

Abstract: This study will be useful for neurological practice to estimate functional outcome or disease severity of natalizumab-PML in primary care settings.

Cited by 25 publications

References 10 publications

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

Natalizumab-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: Findings from an Italian Independent Registry

MRI in the assessment and monitoring of multiple sclerosis: an update on best practice

The role of natalizumab in the treatment of multiple sclerosis: benefits and risks

Contact Info

Product

Resources

About