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- Clanet, M, et al.
(författare)
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A randomized, double-blind, dose-comparison study of weekly interferon beta-1a in relapsing MS
- 2002
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Ingår i: Neurology. - 1526-632X. ; 59:10, s. 1507-1517
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interferon beta-1a (IFNbeta-1a; Avonex) is effective for the treatment of relapsing MS; however, the optimal dose of IFNbeta-1a is not known. Objective: To determine whether IFNbeta-1a 60 mug IM once weekly is more effective than IFNbeta-1a 30 mug IM once weekly in reducing disability progression in relapsing MS. Methods: In a double-blind, parallel-group, dose-comparison study, 802 patients with relapsing MS from 38 centers in Europe were randomized to IFNbeta-1a 30 mug (n = 402) or 60 mug (n = 400) IM once weekly for greater than or equal to36 months. The primary endpoint was disability progression, defined as time to a sustained increase of greater than or equal to1.0 point on the Expanded Disability Status Scale (EDSS) persisting for 6 months. Additional endpoints included relapses, MRI, safety, immunogenicity, and subgroup analyses of disability progression. Results: Both groups showed equal rates of disability progression (hazard ratio, 0.96; 95% CI, 0.77 to 1.20; p = 0.73). In both groups the proportion of subjects with progression of disability by 36 months estimated from Kaplan-Meier curves was 37%. No dose effects were observed on any of the secondary clinical endpoints. Only one MRI measure at one time point, number of new or enlarging T2 lesions at month 36 compared with month 24, showed a difference favoring the 60-mug dose. Both doses were well tolerated; however, slightly higher incidences of flulike symptoms and muscle weakness were observed in the 60-mug group. The incidences of neutralizing antibodies (titers greater than or equal to20) were 2.3% in the 30-mug group and 5.8% in the 60-mug group. Conclusion: There was no difference between IFNbeta-1a 30 mug and 60 mug IM in clinical or MRI measures.
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- Kappos, L, et al.
(författare)
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Neutralizing antibodies and efficacy of interferon beta-1a - A 4-year controlled study
- 2005
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Ingår i: Neurology. - 1526-632X. ; 65:1, s. 40-47
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the incidence and clinical significance of neutralizing antibody (NAb) formation in patients with relapsing multiple sclerosis ( MS) who participated in the European Interferon Beta-1a IM Dose-Comparison Study. Methods. Patients were randomized to treatment with interferon beta-1a (IFN beta-1a) 30 mu g or 60 mu g IM once weekly for up to 4 years. Serum samples obtained at baseline and every 3 months thereafter were screened for the presence of IFN binding antibodies by ELISA. Patients whose results were seropositive on ELISA were screened for the presence of NAbs using an antiviral cytopathic effect assay. Patients were considered to be positive for NAbs ( NAb+) if the baseline NAb titer was 0 and two or more consecutive postbaseline titers were >= 20. Patients were considered to be negative for NAbs ( NAb -) if the baseline NAb titer was 0 and all postbaseline NAb titers were < 5. Results: The proportion of patients who became NAb + was lower in patients who received 30 mu g of IFN beta-1a than in those who received 60 mu g (7/400 [1.8%] vs 19/395 [4.8%]; p = 0.02). The mean time to NAb + status was 14.5 +/- 6.2 months. Compared with patients who remained NAb -, NAb + patients showed the following: higher relapse rates from months 12 to 48 ( p = 0.04), higher rate of mean change ( worsening) in Expanded Disability Status Scale score from baseline to month 48 ( p = 0.01), greater number of T1 gadolinium-enhanced lesions at months 24 and 36 ( p = 0.02 and 0.03), and greater accrual of new or enlarging T2 lesions from month 12 to months 24 and 36 ( p = 0.05 and 0.09) Conclusions: Neutralizing antibodies ( NAbs) to interferon beta-1a (IFN beta-1a), as observed with other IFN beta s used in the treatment of multiple sclerosis, reduce the therapeutic benefits measured by relapses and MRI activity. Data from this study also suggest NAbs to IFN beta-1a reduce treatment benefits as measured by change in Expanded Disability Status Scale score.
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