Contributions
Abstract: P750
Type: Poster
Abstract Category: Therapy - disease modifying - Others
Background: Although hypovitaminosis D is a known risk factor for developing multiple sclerosis (MS), there is no evidence base supporting Vitamin D3 (VD) as a treatment in MS.
Objectives: To evaluate the benefit of add-on therapy with VD 100 kIU twice monthly over 2 years in relapsing MS (RMS) patients treated with subcutaneous interferon beta-1a 44µg 3 times weekly.
Methods: Double blind randomized placebo controlled 2 year multicenter trial on RMS with serum VD levels≤75nmol/L. The primary endpoint was the annualized relapse rate (ARR). Expanded Disability Status Scale (EDSS), magnetic resonance imaging parameters, laboratory monitoring, quality of life and cognitive abilities were secondary endpoints. Intention to treat (ITT) and completers selection were considered as primary and secondary, respectively. The primary analysis was a general linear model featuring Poison regression and negative binomial model for overdispersion adjusting for baseline values and exposure duration as on offset. The sample size was calculated to provide a power of 80% of detecting a ratio rate (RR) as large as 0.75, in assuming an ARR=1.5 for the placebo group and a correlation ratio=0.7, between baseline and final ARR.
Results: 129 patients were randomized: 63 in VD group and 66 in placebo group. A non-significant benefit was found in the VD group (ARR=0.34) compared with placebo (ARR=0.45) with a RR=0.80 ([0.48, 1.32], p=0.379). On the completers sample (n=45 in both VD and placebo groups), we identified a higher and significant VD benefit (RR=0.40, [0.20, 0.81], p=0.011) on ARR and a lower count of new or enlarged weighted lesions (RR=0.22, [0.10, 0.49] p< 0.001 and 0.23, [0.09, 0.57], p=0.001 for T1 and T2 lesions, respectively). No significant difference was found on change in quality of life (p=0.78). The two groups were characterized by a similar safety profile: 11 and 10 patients reported serious treatment emergent adverse events in the VD and placebo group respectively.
Conclusion: Although a strong effect was observed in reducing relapses of 60% on completers (RR=0.40), we failed to find a significant effect of VD on an ITT basis. In spite of an observed clinically relevant effect size of RR=0.80 (20% reduction in relapse rate), the unexpected low relapse rate in the control group (ARR=0.45) underpowered the study. A more thorough statistical analysis of this trial is on the way.
Disclosure:
Pr W. Camu: received lecture fees, honoraria and/or travel expenses refund from Actelion, Biogen, Effik, Merck and Sanofi.
Pr C. Pierrot Deseilligny: received lecture fees and /or hotel/travel expenses from Merck Serono, Novartis and Schering.
Pr P. Hautecoeur: received consulting fees from Merck Serono, Bayer, Biogen, Genzyme, Novartis.
A. Besserve: is an employee of Merck, France
Dr AS. Jean Deleglise: is an employee of Merck, France
Dr P. Lehert: has served as a statistical consultant for several pharmaceutical companies including Merck.
Dr JC. Souberbielle: received lecture fees and/or travel/hotel expenses from DiaSorin, Roche Diagnostics, Abbott, Amgen, Shire, MSD, Lilly and Rottapharm.
Abstract: P750
Type: Poster
Abstract Category: Therapy - disease modifying - Others
Background: Although hypovitaminosis D is a known risk factor for developing multiple sclerosis (MS), there is no evidence base supporting Vitamin D3 (VD) as a treatment in MS.
Objectives: To evaluate the benefit of add-on therapy with VD 100 kIU twice monthly over 2 years in relapsing MS (RMS) patients treated with subcutaneous interferon beta-1a 44µg 3 times weekly.
Methods: Double blind randomized placebo controlled 2 year multicenter trial on RMS with serum VD levels≤75nmol/L. The primary endpoint was the annualized relapse rate (ARR). Expanded Disability Status Scale (EDSS), magnetic resonance imaging parameters, laboratory monitoring, quality of life and cognitive abilities were secondary endpoints. Intention to treat (ITT) and completers selection were considered as primary and secondary, respectively. The primary analysis was a general linear model featuring Poison regression and negative binomial model for overdispersion adjusting for baseline values and exposure duration as on offset. The sample size was calculated to provide a power of 80% of detecting a ratio rate (RR) as large as 0.75, in assuming an ARR=1.5 for the placebo group and a correlation ratio=0.7, between baseline and final ARR.
Results: 129 patients were randomized: 63 in VD group and 66 in placebo group. A non-significant benefit was found in the VD group (ARR=0.34) compared with placebo (ARR=0.45) with a RR=0.80 ([0.48, 1.32], p=0.379). On the completers sample (n=45 in both VD and placebo groups), we identified a higher and significant VD benefit (RR=0.40, [0.20, 0.81], p=0.011) on ARR and a lower count of new or enlarged weighted lesions (RR=0.22, [0.10, 0.49] p< 0.001 and 0.23, [0.09, 0.57], p=0.001 for T1 and T2 lesions, respectively). No significant difference was found on change in quality of life (p=0.78). The two groups were characterized by a similar safety profile: 11 and 10 patients reported serious treatment emergent adverse events in the VD and placebo group respectively.
Conclusion: Although a strong effect was observed in reducing relapses of 60% on completers (RR=0.40), we failed to find a significant effect of VD on an ITT basis. In spite of an observed clinically relevant effect size of RR=0.80 (20% reduction in relapse rate), the unexpected low relapse rate in the control group (ARR=0.45) underpowered the study. A more thorough statistical analysis of this trial is on the way.
Disclosure:
Pr W. Camu: received lecture fees, honoraria and/or travel expenses refund from Actelion, Biogen, Effik, Merck and Sanofi.
Pr C. Pierrot Deseilligny: received lecture fees and /or hotel/travel expenses from Merck Serono, Novartis and Schering.
Pr P. Hautecoeur: received consulting fees from Merck Serono, Bayer, Biogen, Genzyme, Novartis.
A. Besserve: is an employee of Merck, France
Dr AS. Jean Deleglise: is an employee of Merck, France
Dr P. Lehert: has served as a statistical consultant for several pharmaceutical companies including Merck.
Dr JC. Souberbielle: received lecture fees and/or travel/hotel expenses from DiaSorin, Roche Diagnostics, Abbott, Amgen, Shire, MSD, Lilly and Rottapharm.