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Lookup NU author(s): Emeritus Professor David Bates
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Background: The PRISMS study demonstrated significant clinical and MRI benefit at 2 years for interferon-beta -1a, 22 and 44 meg 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-beta -1a, 22 or 44 meg tiw (n = 172; crossover group); others continued blinded treatment with their originally assigned dose, 22 meg (Rx22 group) or 44 meg (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-p-la 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.
Author(s): Francis G, Hughes R, King J, Mitchell P, Joubert J, McLeod J, Parker G, Pollard J, Sindic CJM, Duprez T, Medaer R, Broeckx J, Vanroose E, Carton H, Wilms G, Rice G, Ebers G, Lee DH, Freedman M, Nelson R, Rabinovitch H, Christie S, Avruch L, Oger J, Paty DW, Li D, Wikstrom J, Salonen OLM, Panelius M, Eralinna J, Sonninen P, Rieckmann P, Hahn D, Flachenecker P, Hartung HP, Uitdehaag B, Bertelsmann FW, Barkhof F, Hommes OR, Jongen PJH, Van Doorn PA, Tanghe HLG, Sandberg-Wollheim M, Larsson EM, Lonntoft M, Sallerfors S, Kappos L, Lienert C, Radu EW, Chofflon M, Roth S, Castillo V, Schwieger AF, Hughes RAC, Clews AM, Bingham JB, Barnes D, Clifton AG, Stoy N, Bates D, Coulthard A, Blumhardt LD, Evans SM, Jaspan T, Palace J, Newsom-Davis JM, Byrne JV, Quaghebeur G, Li DKB, Paty DW, Zhao GJ, Riddehough A, Rhodes B, PRISMS Study Grp, Univ British Columbia MS MRI Anal
Publication type: Article
Publication status: Published
ISSN (print): 0028-3878
ISSN (electronic): 1526-632X
Publisher: Lippincott Williams & Wilkins