Abstract Details

Title Serum Concentrations of Natalizumab, Endogenous IgG4, and sVCAM-1 in Natalizumab-Treated PML Patients

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 159

Objective

Background BACKGROUND: Natalizumab is a recombinant humanized anti-? 4 integrin antibody approved for the treatment of relapsing-remitting MS. PML is infrequently associated with natalizumab treatment.

Design/Methods DESIGN/METHODS: Serum concentrations of natalizumab were quantified in natalizumab-treated MS patients with PML (n=21) and without PML (n=560). Also, since natalizumab undergoes half-antibody exchange with endogenous IgG4 in vivo to generate bispecific molecules, serum concentration of IgG4 was measured as a surrogate marker of exposure to unexchanged natalizumab (PML patients, n=28; non-PML patients, n=283). Concentrations of sVCAM, a pharmacodynamic marker of natalizumab, were measured in 10 PML and 173 non-PML patients.

Results RESULTS: No significant difference was observed between median serum concentrations of IgG4 in PML and non-PML patients (225 [micro]g/mL vs 250 [micro]g/mL). Similarly, no significant difference in sVCAM-1 concentrations was noted between PML and non-PML patients either prior to or during natalizumab treatment. The median serum concentrations of natalizumab in PML patients after approximately 12 and 24 months of natalizumab treatment were 21 [micro]g/mL and 31 [micro]g/mL, respectively, and did not differ significantly from those of non-PML patients (20 [micro]g/mL and 27 [micro]g/mL).

Conclusions CONCLUSIONS: Although this analysis was performed on PML samples collected outside of controlled clinical studies and may be confounded by small sample size and varying intervals between natalizumab infusion and sample collection, serum concentrations of natalizumab, endogenous IgG4, and sVCAM-1 do not appear to differ in natalizumab patients who develop PML and those who do not and therefore do not appear to provide a practical approach to stratify patients' risk for developing PML.

Authors/Disclosures
Tatiana Plavina, PhD PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Geoffrey Kuesters	No disclosure on file
	No disclosure on file
Gavin Giovannoni, MD (QMUL)	Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck KGaA. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche-Genentech. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Moderna. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sandoz. Dr. Giovannoni has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Astoria Biologica. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zenas. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Giovannoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Giovannoni has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Medscape.
	No disclosure on file
	No disclosure on file
Ted Yednock, PhD (Annexon Biosciences)	Ted Yednock, PhD has received personal compensation for serving as an employee of Annexon Inc. Ted Yednock, PhD has received personal compensation in the range of $100,000-$499,999 for serving as an officer or member of the Board of Directors for Annexon Inc. Ted Yednock, PhD has stock in Annexon Inc. Ted Yednock, PhD has received intellectual property interests from a discovery or technology relating to health care.
Susan E. Goelz, PhD (myelin repair foundation)	No disclosure on file
Teresa G. Compton	No disclosure on file
Meena Subramanyam, PhD	No disclosure on file

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