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   DIR Return to: TYSABRI (natalizumab)
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       #Post#: 291--------------------------------------------------
       (AAN) Low body weight as surrogate risk factor for PML
   DIR By: agate
       Date: May 8, 2014, 2:06 pm
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       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:
       --- Quote ---
       > [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
       >
       > Objective:
       > To assess the association between body weight and PML
       >
       > Background:
       >
       > 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.
       >
       > Methods:
       >
       > 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.
       >
       > Results:
       >
       > 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.
       >
       > Conclusions:
       >
       > • 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)
       >
       --- End Quote ---
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