Efficacy of subcutaneous interferon β-1a on MRI outcomes in a randomised controlled trial of patients with clinically isolated syndromes
- Nicola De Stefano1,
- Giancarlo Comi2,
- Ludwig Kappos3,
- Mark S Freedman4,
- Chris H Polman5,
- Bernard M J Uitdehaag5,
- Brian Hennessy6,
- Florence Casset-Semanaz7,
- Lorenz Lehr6,
- Bettina Stubinski6,
- Dominic L Jack8,
- Frederik Barkhof9
- 1Department of Neurological & Behavioral Sciences, University of Siena, Siena, Italy
- 2Department of Neurology, Ospedale San Raffaele, Milan, Italy
- 3Departments of Neurology and Biomedicine, University Hospital Basel, Basel, Switzerland
- 4University of Ottawa, Ottawa, Ontario, Canada
- 5VU University Medical Center, Amsterdam, Netherlands
- 6Merck Serono SA, Geneva, Switzerland
- 7EMD Serono, Inc., Billerica, Massachusetts, USA
- 8Caudex Medical, Oxford, UK
- 9Diagnostic Radiology and Image Analysis Center (IAC), VU University Medical Center, Amsterdam, Netherlands
- Correspondence to Dr Nicola De Stefano, Department of Neurological & Behavioral Sciences, University of Siena, Viale Bracci 2, Siena 53100, Italy;
- Received 10 July 2013
- Revised 1 November 2013
- Accepted 5 November 2013
- Published Online First 29 November 2013
Aim The REbif FLEXible dosing in early MS (REFLEX) study compared several brain MRI outcomes in patients presenting with clinically isolated syndromes suggestive of multiple sclerosis and treated with two dose-frequencies of subcutaneous interferon (IFN) β-1a or placebo.
Methods Patients were randomised (1:1:1) to IFN β-1a, 44 µg subcutaneously three times a week or once a week, or placebo three times a week for up to 24 months. MRI scans were performed every 3 months, or every 6 months if the patient developed clinically definite multiple sclerosis. End points analysed included: number of combined unique active lesions per patient per scan; numbers and volumes of new T2, T1 hypointense and gadolinium-enhancing (Gd+) lesions per patient per scan; and brain volume.
Results 517 patients were randomised (intent-to-treat population: subcutaneous IFN β-1a three times a week, n=171; subcutaneous IFN β-1a once a week, n=175; placebo, n=171). Combined unique active lesions were lower in patients treated with subcutaneous IFN β-1a versus placebo (mean (SD) lesions per patient per scan: three times a week 0.6 (1.15); once a week 1.23 (4.26); placebo 2.70 (5.23); reduction versus placebo: three times a week 81%; once a week 63%; p<0.001) and with three times a week versus once a week (48% reduction; p=0.002). The mean numbers of new T2, T1 hypointense and Gd+ lesions were all significantly lower in the two active treatment arms compared with placebo (p≤0.004 for three times a week or once a week) and in the three times a week group compared with once a week (p≤0.012).
Conclusions Both subcutaneous IFN β-1a 44 µg regimens improved MRI outcomes versus placebo, with the three times a week regimen having a more pronounced effect than once a week dosing.
Trial registration clinicaltrial.gov identifier, NCT00404352.
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