Abstract Details

Title Clinical Consequences of Persistently High-Titer Neutralizing Antibodies in Patients with Multiple Sclerosis - Results from the German Reference Lab

Topic MS and Related Diseases

Presentation(s) P01 - (-)

Poster/Presentation
Number 192

Objective

Background BACKGROUND: Longterm treatment with IFNb is an approved basic therapy for patients with multiple sclerosis. In 2-47 % of patients however, NAbs may develop and, if high-titer and persistent, may limit the bioavailability of IFNb and its clinical benefits. Thus, European guidelines recommend to switch to other therapeutic options in these patients.

Design/Methods DESIGN/METHODS: Serum samples sent in nationwide by treating neurologists and MS centers for NABs testing were subjected to an established capture ELISA to screen for binding antibodies and subsequently to a luciferase reporter gene assay for the quantitative detection of NAbs. Patients with two highly positive NABs samples (> 100 TRU/mL) sent in at least three months apart were identified and the treating physicians asked by mail to provide follow-up information by means of a standardized questionnaire.

Results RESULTS: Between January 2008 and June 2010 serum samples of 2,025 patients were sent for first-time NAb testing (mean age: 39.3±10.8 years; 71.7 % female; 80.4 % relapsing-remitting MS; 96.6 % on current IFNb treatment). NAbs were detectable in 27 % of samples, 17.5 % of which were deemed high-titer NAbs. NAbs were significantly more frequent in patients treated with IFNb-1b s.c. than IFNb-1a s.c. and were lowest with IFNb-1a i.m. (40.3 % vs. 28.2 % vs. 8.5 %; p<0.0001, Chi-square). 25 patients with persistently high-titer NAbs were identified, of which 20 questionnaires were returned; therapy was amended in 16 patients: 75 % were switched to glatiramer actetate (GA), 18.7 % were escalated to more potent therapies.

Conclusions CONCLUSIONS: The overall prevalence of persistently high-titer NAbs is low. When detected, the majority of treating neurologists opted to switch to GA rather than to escalate therapy or to continue IFNb.

Authors/Disclosures
Til Menge, MD, FAAN (Zentrum Fur Neurologie Und Neuropsychiatrie) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung 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. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
	No disclosure on file
	No disclosure on file

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