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Background: The PRISMS study demonstrated significant clinical and MRI benefit at 2 years for interferon-β-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-β-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-β-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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Published In

Volume 56Number 12June 26, 2001
Pages: 1628-1636
PubMed: 11425926

Publication History

Received: November 15, 2000
Accepted: April 2, 2001
Published online: June 26, 2001
Published in print: June 26, 2001


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Affiliations & Disclosures

The PRISMS (Prevention of Relapses and Disability by Interferon-β-1a Subcutaneously in Multiple Sclerosis) Study Group
the University of British Columbia MS/MRI Analysis Group


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: [email protected] Address reprint requests to Dr. Gordon Francis, 15 ch des Mines, Geneva, Switzerland 1202; e-mail: [email protected].

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