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Address correspondence to Dr. Richard Hughes, Department of Neuroimmunology, Guy’s, King’s and St. Thomas’ School of Medicine, Guy’s Hospital, London SE1 9RT, UK; e-mail: richard.a.hughes{at}kcl.ac.ukAddress reprint requests to Dr. Gordon Francis, 15 ch des Mines, Geneva, Switzerland 1202; e-mail: gordon.francis@serono.com.
BACKGROUND: The PRISMS study demonstrated significant clinical and MRI benefit at 2 years for interferon-ß-1a, 22 and 44 mcg thrice weekly (tiw), compared with placebo in relapsing–remitting MS. Years 3 and 4 extension study results are reported.
METHODS: Patients initially receiving placebo were randomized to blinded interferon-ß-1a, 22 or 44 mcg tiw (n = 172; crossover group); others continued blinded treatment with their originally assigned dose, 22 mcg (Rx22 group) or 44 mcg (Rx44 group) tiw (n = 167 per group). Patients had 3- to 6-month clinical and annual MRI assessments.
RESULTS: Relapse rates for 4 years were 1.02 (crossover), 0.80 (Rx22, p < 0.001), and 0.72 (Rx44, p < 0.001); the dose effect approached significance (p = 0.069; risk ratio, 0.88; 95% CI, 0.76–1.01). Crossover groups showed reductions in relapse count, MRI activity, and lesion-burden accumulation with interferon-ß-1a compared with their placebo period (p < 0.001 both doses). Time to sustained disability progression was prolonged by 18 months in the Rx44 group compared with the crossover group (p = 0.047). Rx22 and Rx44 reduced new T2 lesion number and lesion burden compared with crossover (p < 0.001); Rx44 was superior to Rx22 on several clinical and MRI outcomes. Persistent neutralizing antibodies developed in 14.3% (Rx44) and 23.7% (Rx22) of patients and were associated with reduced efficacy.
CONCLUSIONS: Clinical and MRI benefit continued for both doses up to 4 years, with evidence of dose response. Outcomes were consistently better for patients treated for 4 years than for patients in crossover groups. Efficacy decreased with neutralizing antibody formation.
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|
|
|
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|
|
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|
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|
|
|
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|
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|
|
|
|
|
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|
|
|
|
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|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
M S Freedman, G S Francis, E A. Sanders, G P. Rice, P O'Connor, G Comi, P Duquette, L Metz, T J Murray, J-P Bouchard, et al. Randomized study of once-weekly interferon {beta}-1a therapy in relapsing multiple sclerosis: three-year data from the OWIMS study Multiple Sclerosis, February 1, 2005; 11(1): 41 - 45. [Abstract] [PDF]
|
|
|
|
|
|
K E. O'Rourke and M Hutchinson Stopping beta-interferon therapy in multiple sclerosis: an analysis of stopping patterns Multiple Sclerosis, February 1, 2005; 11(1): 46 - 50. [Abstract] [PDF]
|
|
|
|
|
|
J D Fisk, M G Brown, I S Sketris, L M Metz, T J Murray, and K J Stadnyk A comparison of health utility measures for the evaluation of multiple sclerosis treatments J. Neurol. Neurosurg. Psychiatry, January 1, 2005; 76(1): 58 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J van Holten, K Pavelka, J Vencovsky, H Stahl, B Rozman, M Genovese, A J Kivitz, J Alvaro, G Nuki, D E Furst, et al. A multicentre, randomised, double blind, placebo controlled phase II study of subcutaneous interferon beta-1a in the treatment of patients with active rheumatoid arthritis Ann Rheum Dis, January 1, 2005; 64(1): 64 - 69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
D. R. Jeffery Use of combination therapy with immunomodulators and immunosuppressants in treating multiple sclerosis Neurology, December 28, 2004; 63(12_suppl_6): S41 - S46. [Abstract] [Full Text]
|
|
|
|
|
|
R. Bakshi, G. J. Hutton, J. R. Miller, and E.-W. Radue The use of magnetic resonance imaging in the diagnosis and long-term management of multiple sclerosis Neurology, December 14, 2004; 63(11_suppl_5): S3 - S11. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
T. K. Vartanian, S. S. Zamvil, E. Fox, and P. S. Sorensen Neutralizing antibodies to disease-modifying agents in the treatment of multiple sclerosis Neurology, December 14, 2004; 63(11_suppl_5): S42 - S49. [Abstract] [Full Text]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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