MD1003 in progressive multiple sclerosis: 24-month brain MRI results of the MS-SPI trial
ECTRIMS Online Library. Arnold D. 10/26/17; 202483; 130
Dr. Douglas L Arnold
Dr. Douglas L Arnold
Contributions Biography
Abstract

Abstract: 130

Type: Oral

Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS

Introduction: MS-SPI was a 12-month (M) randomised, double-blind, placebo-controlled trial of the effects of MD1003 (high-dose biotin) in patients with progressive, non-clinically active multiple sclerosis (MS). In the open-label extension phase, all patients received MD1003. Results of a brain volumetric MRI follow-up sub-study are presented here.
Methods: Sequences were standardised and tested between the 6 centres included. Images were centralised to the Shanoir platform and analysed in 2 independent centres (INSERM, Toulouse; NeuroRx, Montreal).
MRIs were performed at M0, M12 and M24 for 74 patients (MD1003>MD1003: 49; placebo>MD1003: 25). Normalised volumes of the whole brain (WBV), white (WMV) and grey matter (GMV) at baseline were analysed using SIENAX in 66 patients (MD1003>MD1003: 44; placebo>MD1003: 22). Subsequent volume changes were analysed using SIENA and paired Jacobian integration.
Results: A decrease in WBV and GMV measures was observed at M12 in the MD1003 arm compared to placebo. Differences were statistically significant for the WBV % change and for the GMV % change. No differences were observed for the WMV % change. At M24, the change from baseline in WBV, GMV and WMV were relatively constant in the MD1003 group, which continued on treatment, compared to M12. The placebo group, in which changes from baseline had been moderate in the first 12 months, experienced a decrease across all volumetric measures when switched to MD1003 at Month 12 and this was maintained for 12 months. At M24, the decrease was similar in the placebo>MD1003 group and in the MD1003>MD1003 group.
Conclusions: Volumetric analyses performed independently and blindly by two different reading centres indicated a decrease in WBV and GMV in the MD1003 arm compared to placebo. A decrease in these volumes was also observed in the placebo group switched to MD1003. No differences between groups were observed at M24, after the placebo arm had been switched to active treatment.
Overall, these results are consistent with a pseudo-atrophy phenomenon linked to a decrease in brain water volume following the initiation of treatment with MD1003. This pseudo-atrophy phenomenon may be a consequence of increased energy production triggered by high doses of biotin.
Disclosure: Douglas L. Arnold has served on advisory boards, received speaker honoraria or served as a consultant for Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedDay, MedImmune, Mitsubishi, Novartis, Receptos/Celgene and Sanofi-Aventis; has received grants from Biogen and Novartis; and has an equity interest in NeuroRx Research.
Jean Pelletier has received consulting fees and travel grants from Biogen, Sanofi Genzyme, Novartis, Teva, Merck Serono, Roche and MedDay, and unconditional research grants from Biogen, Novartis, Roche and Merck Serono.
Isabelle Berry has nothing to disclose.
Christian Barillot has received consulting fees and travels from Novartis.
Betty Jean has nothing to disclose.
Damien Galanaud has received consulting fees from MedDay.
Laurent Pierot has nothing to disclose.
Jean-Philippe Ranjeva participated in the acquisition and post-processing of the MedDay protocol.
Gilles Edan has received personal fees from Bayer, and grants and personal fees from Merck Serono, Teva, Biogen Idec, Novartis and Sanofi.
Pierre Clavelou has received honoraria and consulting fees from Almirall, MedDay, Merck, Novartis, Roche, Sanofi Genzyme and Teva, and research support from Biogen, Merck and Novartis.
Frédéric Sedel is an employee of MedDay.
Ayman Tourbah has received, in the last year, consulting and lecturing fees, travel grants and research support from MedDay, Biogen Idec, Sanofi Genzyme, Novartis, Merck Serono, Teva Pharma and Roche.
Caroline Papeix has received compensation as a consultant, advisory board member or speaker for Roche, Novartis, Biogen, Teva-Aventis, Sanofi-Genzyme, and MedDay.

Abstract: 130

Type: Oral

Abstract Category: Therapy - disease modifying - 31 Treatment of progressive MS

Introduction: MS-SPI was a 12-month (M) randomised, double-blind, placebo-controlled trial of the effects of MD1003 (high-dose biotin) in patients with progressive, non-clinically active multiple sclerosis (MS). In the open-label extension phase, all patients received MD1003. Results of a brain volumetric MRI follow-up sub-study are presented here.
Methods: Sequences were standardised and tested between the 6 centres included. Images were centralised to the Shanoir platform and analysed in 2 independent centres (INSERM, Toulouse; NeuroRx, Montreal).
MRIs were performed at M0, M12 and M24 for 74 patients (MD1003>MD1003: 49; placebo>MD1003: 25). Normalised volumes of the whole brain (WBV), white (WMV) and grey matter (GMV) at baseline were analysed using SIENAX in 66 patients (MD1003>MD1003: 44; placebo>MD1003: 22). Subsequent volume changes were analysed using SIENA and paired Jacobian integration.
Results: A decrease in WBV and GMV measures was observed at M12 in the MD1003 arm compared to placebo. Differences were statistically significant for the WBV % change and for the GMV % change. No differences were observed for the WMV % change. At M24, the change from baseline in WBV, GMV and WMV were relatively constant in the MD1003 group, which continued on treatment, compared to M12. The placebo group, in which changes from baseline had been moderate in the first 12 months, experienced a decrease across all volumetric measures when switched to MD1003 at Month 12 and this was maintained for 12 months. At M24, the decrease was similar in the placebo>MD1003 group and in the MD1003>MD1003 group.
Conclusions: Volumetric analyses performed independently and blindly by two different reading centres indicated a decrease in WBV and GMV in the MD1003 arm compared to placebo. A decrease in these volumes was also observed in the placebo group switched to MD1003. No differences between groups were observed at M24, after the placebo arm had been switched to active treatment.
Overall, these results are consistent with a pseudo-atrophy phenomenon linked to a decrease in brain water volume following the initiation of treatment with MD1003. This pseudo-atrophy phenomenon may be a consequence of increased energy production triggered by high doses of biotin.
Disclosure: Douglas L. Arnold has served on advisory boards, received speaker honoraria or served as a consultant for Acorda, Biogen, F. Hoffmann-La Roche Ltd, MedDay, MedImmune, Mitsubishi, Novartis, Receptos/Celgene and Sanofi-Aventis; has received grants from Biogen and Novartis; and has an equity interest in NeuroRx Research.
Jean Pelletier has received consulting fees and travel grants from Biogen, Sanofi Genzyme, Novartis, Teva, Merck Serono, Roche and MedDay, and unconditional research grants from Biogen, Novartis, Roche and Merck Serono.
Isabelle Berry has nothing to disclose.
Christian Barillot has received consulting fees and travels from Novartis.
Betty Jean has nothing to disclose.
Damien Galanaud has received consulting fees from MedDay.
Laurent Pierot has nothing to disclose.
Jean-Philippe Ranjeva participated in the acquisition and post-processing of the MedDay protocol.
Gilles Edan has received personal fees from Bayer, and grants and personal fees from Merck Serono, Teva, Biogen Idec, Novartis and Sanofi.
Pierre Clavelou has received honoraria and consulting fees from Almirall, MedDay, Merck, Novartis, Roche, Sanofi Genzyme and Teva, and research support from Biogen, Merck and Novartis.
Frédéric Sedel is an employee of MedDay.
Ayman Tourbah has received, in the last year, consulting and lecturing fees, travel grants and research support from MedDay, Biogen Idec, Sanofi Genzyme, Novartis, Merck Serono, Teva Pharma and Roche.
Caroline Papeix has received compensation as a consultant, advisory board member or speaker for Roche, Novartis, Biogen, Teva-Aventis, Sanofi-Genzyme, and MedDay.

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