A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis
- Merja Soilu-Hänninen1,
- Julia Åivo1,
- Britt-Marie Lindström2,
- Irina Elovaara3,
- Marja-Liisa Sumelahti3,
- Markus Färkkilä4,
- Pentti Tienari4,
- Sari Atula4,
- Taneli Sarasoja5,
- Lauri Herrala6,
- Irma Keskinarkaus7,
- Johanna Kruger7,
- Timo Kallio8,
- Maria A Rocca9,
- Massimo Filippi9
- 1Department of Neurology, University of Turku, Turku, Finland
- 24Pharma Ltd, Turku, Finland
- 3Department of Neurology, University of Tampere, Tampere, Finland
- 4Department of Neurology, University of Helsinki, Helsinki, Finland
- 5Central Hospital of Central Finland, Jyväskylä, Finland
- 6Central Hospital of Ostrobotnia, Finland
- 7Department of Neurology, University of Oulu, Oulu, USA
- 8Terveystalo Clinical Research, Sibeliuksenkatu, Turku, Finland
- 9Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
- Correspondence to Dr M H Soilu-Hänninen, University Hospital of Turku, Department of Neurology, Kiinamyllynkatu 4-8, Turku FIN-20520, Finland;
Contributors Study concept and design: MHS-H. Acquisition of the data: SA, IE, LH, IK, JK, TS, MHS-H, M-JS and PT. Analysis and interpretation of the data: MHS-H, JÅ and B-ML. Drafting of the manuscript: MHS-H, B-ML, TK, MF and JÅ. Critical review of the manuscript for important intellectual content: all authors. Statistical analysis: B-ML, MHS-H and JÅ. Obtained funding: MHS-H. Administrative, technical and material support: IE, MF, LH, TS and IK. Study supervision: MHS-H. MRI analysis centre: MF (chair), MAR, P Valsasina, S Mesaros, V Barcella, A Meani and S Sala. All authors have read and approved the manuscript.
- Received 24 November 2011
- Revised 28 January 2012
- Accepted 30 January 2012
- Published Online First 22 February 2012
Objectives To study the safety and efficacy of vitamin D3 as an add on therapy to interferon β-1b (IFNB) in patients with multiple sclerosis (MS).
Methods 1 year, double blind, placebo controlled, randomised study in 66 MS patients. The primary outcomes were T2 burden of disease (BOD) on MRI scans, proportion of patients with serum levels of 25-hydroxyvitamin D (25(OH)D) ≥85 nmol/l or intact parathyroid hormone (PTH) ≤20 ng/l, and number of adverse events. Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions, annual relapse rate, changes in the Expanded Disability Status Scale score, timed 25 foot walk test and timed 10 foot tandem walk tests.
Results Median change in BOD was 287 mm3 in the placebo group and 83 mm3 in the vitamin D group (p=0.105). Serum levels of 25(OH)D increased from a mean of 54 (range 19–82) nmol/l to 110 (range 67–163) nmol/l in the vitamin D group. 84% of patients reached a serum 25(OH)D level >85 nmol/l in the vitamin D group and 3% in the placebo group (p<0.0001). Patients in the vitamin D group showed fewer new T2 lesions (p=0.286) and a significantly lower number of T1 enhancing lesions (p=0.004), as well as a tendency to reduced disability accumulation (p=0.071) and to improved timed tandem walk (p=0.076). There were no significant differences in adverse events or in the annual relapse rate.
Conclusion Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS.
Trial registration number EudraCT number 2007-001958-99 and ClinicalTrialsGov number NCT01339676.
Funding The study was funded by an unrestricted grant from Bayer. MS-H was funded by the Finnish MS Foundation and by the Finnish Brain Foundation.
Competing interests None.
Ethics approval The study was approved by Turku University Ethics Committee and the Finnish Agency of Medicines.
Provenance and peer review Not commissioned; externally peer reviewed.