Contributions
Abstract: P878
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: MD1003 (high dose Pharmaceutical grade Biotin) was recently shown to improve disability in some patients with progressive MS (PMS) (Tourbah et al., 2016) and is available in France through an expanded access programme.We monitored disability progression in a cohort of 91 patients treated with MD1003 for 12 months (M)using clinical parameters (expanded disability status scale [EDSS]; timed 25-foot walk [TW25]) and magnetic resonance imaging (MRI) measures (T1 gadolinium-enhancing lesions). Among those patients, 22 (24.2 %) patients showed clinical or/and MRI worsening at M12 of MD1003 treatment.
Objective: To investigate the potential immunomodulatory effect of MD1003 in patients with progressive MS who had worsened under MD1003 treatment.
Methods: We analysed lymphocytes, monocytes, and dendritic cells frequencies, and their major cell subsets in blood samples from patients treated with MD1003 at baseline (M0), M6, and M12. We compared at each time-point the cell frequencies between patients who did not progress and patients who showed clinical worsening, and between patients who did not progress and patients who showed MRI worsening (Mann-Whitney 2 sided test).
Results: Clinical worsening was associated with a significant decrease (P=0.0153) from baseline in whole lymphocyte number at M6 but not M12, and with a significant decrease from baseline in the number of CD4+ T cells (P=0.0442) and of CD8+ T cells (P=0.0076) at M12; the CD4+ T cell/CD8+ T cell ratio was also upset at M12 (P=0.0444). MRI worsening was associated with a significant decrease (P=0.0414) in the whole lymphocyte frequency and in the frequency of plasmablasts/plasma cells (P=0.0122) from baseline at M6, and with a significant increase (P=0.0126) in class-switched memory IgD-CD27+ B cells at M12.
Conclusion: In patients treated with high dose Pharmaceutical grade Biotin (MD1003) for 12 months, clinical and MRI worsening were associated with distinct changes in immune cell frequencies. This suggests a potential immunomodulatory effect of MD1003 in those patients.
Disclosure: J. Ciron: nothing to disclose, B. Pignolet: nothing to disclose, F. Bucciarelli: nothing to disclose, L. Scandella: nothing to disclose, F. Lerebours: nothing to disclose, G. Dorcet: nothing to disclose, C. Rabadeux: nothing to disclose, N. Freitas: nothing to disclose, F. Bonneville: nothing to disclose, D. Biotti received speaker honoraria from Teva, Merck, Roche, Biogen, Novartis, D. Brassat received research grant from EU FP7, 305477-2012, EU Marie Curie action 2008 (Co I) ABIRISK (co I), French ministery of health -2008 (PHRC), French MS society 2009, 2012, 2017. Lectures, congress invitation, board participation with Bayer, Biogen, Medday, Merck, Novartis, Roche, Sanofi-Genzyme and Teva.
Abstract: P878
Type: Poster Sessions
Abstract Category: Therapy - Immunomodulation/Immunosuppression
Background: MD1003 (high dose Pharmaceutical grade Biotin) was recently shown to improve disability in some patients with progressive MS (PMS) (Tourbah et al., 2016) and is available in France through an expanded access programme.We monitored disability progression in a cohort of 91 patients treated with MD1003 for 12 months (M)using clinical parameters (expanded disability status scale [EDSS]; timed 25-foot walk [TW25]) and magnetic resonance imaging (MRI) measures (T1 gadolinium-enhancing lesions). Among those patients, 22 (24.2 %) patients showed clinical or/and MRI worsening at M12 of MD1003 treatment.
Objective: To investigate the potential immunomodulatory effect of MD1003 in patients with progressive MS who had worsened under MD1003 treatment.
Methods: We analysed lymphocytes, monocytes, and dendritic cells frequencies, and their major cell subsets in blood samples from patients treated with MD1003 at baseline (M0), M6, and M12. We compared at each time-point the cell frequencies between patients who did not progress and patients who showed clinical worsening, and between patients who did not progress and patients who showed MRI worsening (Mann-Whitney 2 sided test).
Results: Clinical worsening was associated with a significant decrease (P=0.0153) from baseline in whole lymphocyte number at M6 but not M12, and with a significant decrease from baseline in the number of CD4+ T cells (P=0.0442) and of CD8+ T cells (P=0.0076) at M12; the CD4+ T cell/CD8+ T cell ratio was also upset at M12 (P=0.0444). MRI worsening was associated with a significant decrease (P=0.0414) in the whole lymphocyte frequency and in the frequency of plasmablasts/plasma cells (P=0.0122) from baseline at M6, and with a significant increase (P=0.0126) in class-switched memory IgD-CD27+ B cells at M12.
Conclusion: In patients treated with high dose Pharmaceutical grade Biotin (MD1003) for 12 months, clinical and MRI worsening were associated with distinct changes in immune cell frequencies. This suggests a potential immunomodulatory effect of MD1003 in those patients.
Disclosure: J. Ciron: nothing to disclose, B. Pignolet: nothing to disclose, F. Bucciarelli: nothing to disclose, L. Scandella: nothing to disclose, F. Lerebours: nothing to disclose, G. Dorcet: nothing to disclose, C. Rabadeux: nothing to disclose, N. Freitas: nothing to disclose, F. Bonneville: nothing to disclose, D. Biotti received speaker honoraria from Teva, Merck, Roche, Biogen, Novartis, D. Brassat received research grant from EU FP7, 305477-2012, EU Marie Curie action 2008 (Co I) ABIRISK (co I), French ministery of health -2008 (PHRC), French MS society 2009, 2012, 2017. Lectures, congress invitation, board participation with Bayer, Biogen, Medday, Merck, Novartis, Roche, Sanofi-Genzyme and Teva.