Author Topic: (AAN) Low body weight as surrogate risk factor for PML  (Read 58 times)

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Offline agate

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(AAN) Low body weight as surrogate risk factor for PML
« on: May 08, 2014, 10:06:53 am »
This study suggests that it might be very important to adjust the Tysabri dosage in close correlation with the patient's weight.

Presented at the annual AAN conference in Philadelphia, April 29, 2014:

[P2.244] Low Body Weight as a Potential Surrogate Risk Factor for Progressive Multifocal Leukoencephalopathy

John Foley,1Mark Gudesblatt,2Myassar Zarif,3Ellen Lathi4

1Salt Lake City, UT, USA, 2Patchogue, NY, USA, 3Mount Sinai, NY, USA, 4Boston, MA, USA

To assess the association between body weight and PML


Patient weight as a risk marker for progressive multifocal leukoencephalopathy (PML) has been previously proposed by our group. Data previously presented suggests that weight may serve as a surrogate for natalizumab drug concentration and saturation with higher levels found in lower weight populations.

Additional support for an association of weight and the pharmacokinetics of natalizumab is provided in the natalizumab label which states clearance increases with body weight.


A real world cohort of 934 patients was obtained from three multiple sclerosis clinics in the US in addition to 826 patients from Sweden. A cohort of 36 PML patients from multiple clinics throughout the US and EU was compared by weight, age and therapy duration.


The US natalizumab infusing real world population (median 77 kg) is significantly heavier than the Swedish population (median 69 kg). The PML population weights (median 65.5 kg) were similar in both EU and US groups. When comparing a US infusing population versus a US PML population a statistically significant difference is observed. The US population is significantly older than the EU population and appears to be older than those patients studied in the pivotal trials. Data regarding the association of body weights to natalizumab concentration and saturation will be presented. PML prevalence data in both the US and the EU will also be presented.


  A significant difference in weight is seen between the US population and both the Swedish and PML population cohorts.

Body weights may serve as a surrogate marker given the absence of commercially available natalizumab concentration or lymphocyte saturation levels.

Could the differences that are seen in PML prevalence between US and EU populations be at least partially explained by the population weight disparities with higher body weights providing a protective effect against PML development?

Category - MS and CNS Inflammatory Disease: Clinical Science

P2: Poster Session II: MS and CNS Inflammatory Disease: Progressive Multifocal Leukoencephalopathy Risk (7:30 AM-11:00 AM)
MS Speaks--online for 12 years

SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.