Abstract Details

Title The Study of IFN? Bioactivity Loss by MxA mRNA Quantification Patients Allows the Prediction of Disability Progression in Multiple Sclerosis Patients

Topic MS and Related Diseases

Presentation(s) P04 - (-)

Poster/Presentation
Number 140

Objective

Background BACKGROUND: The detection of anti-IFN? antibodies by BAb, NAb or MxA quantification is not always routinely performed in the clinical setting because its correlation with the measures of clinical outcome is still debated. Analogously, the role of IFNAR subunits/isoforms modulation on IFN? bioactivity is not clearly established.

Design/Methods DESIGN/METHODS: MS patients naive for IFN? therapy (# 118) were enrolled in a multi-center longitudinal study and followed up every 6 months for 36 months. MxA and IFNAR mRNA was quantified by Real-Time PCR, BAbs were detected by radioimmunoprecipitation and NAbs by cytopathic effect inhibition assay. The presence of at least 1-point EDSS increase after 24 or 36 months was considered the marker of disease progression. Statistical analysis was performed by linear mixed-models and logistic regression.

Results RESULTS: MxA induction was impaired in the presence of BAbs and NAbs, and the response to IFN? therapy was extremely heterogeneous, including patients with stable or transitory and early or late loss of IFN? bioactivity (BAb+/NAb+/MxA-). Among these measures of bioactivity loss, only MxA could be correlated to disease worsening, because its average level over the 6-to-24 month period, when adjusted for the risk of relapse, predicted an increased risk of 1-point-EDSS increase after 24 months (Odds-Ratio for each log2MxA: 0.53; confidence interval: 0.31-0.93). IFNAR subunits/isoforms modulation did not induce a loss of IFN? bioactivity; indeed, higher levels of the soluble isoform transcript were associated with higher MxA values.

Conclusions CONCLUSIONS: MxA quantification predicted a risk of disability progression likely due to IFN? bioactivity decrease. Together with its feasibility in the routine laboratory setting, these data further warrant the quantification of MxA mRNA as the primary tool for IFN? therapy monitoring.

Authors/Disclosures
Federico Serana PRESENTER	No disclosure on file
Luisa Imberti	No disclosure on file
Maria P. Amato, PhD (Ospedale Di Careggi)	Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation for serving as an employee of AOU Careggi. Dr. Amato has received personal compensation for serving as an employee of AOUCareggi. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Dr. Amato has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Amato 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. Amato 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. Amato 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. Amato 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. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi genzyme. The institution of Dr. Amato has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene BMS. The institution of Dr. Amato has received research support from Merck. The institution of Dr. Amato has received research support from Biogen. The institution of Dr. Amato has received research support from Roche.
Claudio Gasperini, MD	Dr. Gasperini has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche, Merck, Genzyme, Novartis,Bayer, Teva, Almirall.
Angelo Ghezzi, MD	No disclosure on file
Marilyn R. Semenchuk, PharmD, MSc	No disclosure on file
Vittorio Martinelli (S. Raffaele Hospital)	Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis, Biogen, Sanofi Genzyme, TEVA and Merck. Dr. Martinelli has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck .
Leandro Provinciali, MD (Istituto Malattie Sistema Nervoso)	No disclosure on file
Maria Rosa Rottoli, MD	No disclosure on file
	No disclosure on file
Sergio Stecchi, MD (Multiple Sclerosis Center)	No disclosure on file
Michele Maria Vecchio, MD (Az.Osp.S.Elia)	No disclosure on file
Mauro Zaffaroni (Teva Pharma Italia)	No disclosure on file
Ruggero Capra, MD	Dr. Capra has nothing to disclose.

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