Interferon β-1a in relapsing multiple sclerosis: four-year extension of the European IFNβ-1a Dose-C omparison Study

Background: Multiple sclerosis (MS) is a chronic disease requiring long-term monitoring of treatment. Objective: To assess the four-year clinical efficacy of intramuscular (IM) IFNb-1a in patients with relapsing MS from the European IFNb-1a Dose-C omparison Study. Methods: Patients who completed 36 months of treatment (Part 1) of the European IFNb-1a Dose-C omparison Study were given the option to continue double-blind treatment with IFNb-1a 30 mcg or 60 mcg IM once weekly (Part 2). Analyses of 48-month data were performed on sustained disability progression, relapses, and neutralizing antibody (NA b) formation. Results: O f 608/802 subjects who completed 36 months of treatment, 493 subjects continued treatment and 446 completed 48 months of treatment and follow-up. IFNb-1a 30 mcg and 60 mcg IM once weekly were equally effective for up to 48 months. There were no significant differences between doses over 48 months on any of the clinical endpoints, including rate of disability progression, cumulative percentage of patients who progressed (48 and 43, respectively), and annual relapse rates; relapses tended to decrease over 48 months. The incidence of patients who were positive for NAbs at any time during the study was low in both treatment groups. Conclusion: C ompared with 60-mcg IM IFNb-1a once weekly, a dose of 30 mcg IM IFNb-1a once weekly maintains the same clinical efficacy over four years

Fatal natalizumab-associated progressive multifocal leukoencephalopathy with initial low JCV antibody index in a multiple sclerosis patient

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Natalizumab plus interferon beta-1a for relapsing multiple sclerosis

.AbstractBackgroundInterferon beta is used to modify the course of relapsing multiple sclerosis. Despiteinterferon beta therapy, many patients have relapses. Natalizumab, an α4 integrinantagonist, appeared to be safe and effective alone and when added to interferonbeta-1a in preliminary studies.MethodsWe randomly assigned 1171 patients who, despite interferon beta-1a therapy, hadhad at least one relapse during the 12-month period before randomization to receivecontinued interferon beta-1a in combination with 300 mg of natalizumab (589patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks.The primary end points were the rate of clinical relapse at 1 year and the cumulativeprobability of disability progression sustained for 12 weeks, as measured by theExpanded Disability Status Scale, at 2 years.ResultsCombination therapy resulted in a 24 percent reduction in the relative risk of sustaineddisability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61to 0.96; P = 0.02). Kaplan–Meier estimates of the cumulative probability of progressionat two years were 23 percent with combination therapy and 29 percent withinterferon beta-1a alone. Combination therapy was associated with a lower annualizedrate of relapse over a two-year period than was interferon beta-1a alone (0.34vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T2-weighted magneticresonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combinationtherapy were anxiety, pharyngitis, sinus congestion, and peripheral edema.Two cases of progressive multifocal leukoencephalopathy, one of which was fatal,were diagnosed in natalizumab-treated patients.ConclusionsNatalizumab added to interferon beta-1a was significantly more effective than interferonbeta-1a alone in patients with relapsing multiple sclerosis. Additional researchis needed to elucidate the benefits and risks of this combination treatment.(ClinicalTrials.gov number, NCT00030966.

Natalizumab plus interferon beta-1a for relapsing multiple sclerosis.

Item does not contain fulltextBACKGROUND: Interferon beta is used to modify the course of relapsing multiple sclerosis. Despite interferon beta therapy, many patients have relapses. Natalizumab, an alpha4 integrin antagonist, appeared to be safe and effective alone and when added to interferon beta-1a in preliminary studies. METHODS: We randomly assigned 1171 patients who, despite interferon beta-1a therapy, had had at least one relapse during the 12-month period before randomization to receive continued interferon beta-1a in combination with 300 mg of natalizumab (589 patients) or placebo (582 patients) intravenously every 4 weeks for up to 116 weeks. The primary end points were the rate of clinical relapse at 1 year and the cumulative probability of disability progression sustained for 12 weeks, as measured by the Expanded Disability Status Scale, at 2 years. RESULTS: Combination therapy resulted in a 24 percent reduction in the relative risk of sustained disability progression (hazard ratio, 0.76; 95 percent confidence interval, 0.61 to 0.96; P=0.02). Kaplan-Meier estimates of the cumulative probability of progression at two years were 23 percent with combination therapy and 29 percent with interferon beta-1a alone. Combination therapy was associated with a lower annualized rate of relapse over a two-year period than was interferon beta-1a alone (0.34 vs. 0.75, P<0.001) and with fewer new or enlarging lesions on T(2)-weighted magnetic resonance imaging (0.9 vs. 5.4, P<0.001). Adverse events associated with combination therapy were anxiety, pharyngitis, sinus congestion, and peripheral edema. Two cases of progressive multifocal leukoencephalopathy, one of which was fatal, were diagnosed in natalizumab-treated patients. CONCLUSIONS: Natalizumab added to interferon beta-1a was significantly more effective than interferon beta-1a alone in patients with relapsing multiple sclerosis. Additional research is needed to elucidate the benefits and risks of this combination treatment. (ClinicalTrials.gov number, NCT00030966.)

Natalizumab plus interferon beta-1a reduces lesion formation in relapsing multiple sclerosis

The SENTINEL study showed that the addition of natalizumab improved outcomes for patients with relapsing multiple sclerosis (MS)who had experienced disease activitywhile receiving interferon beta-1a (IFNβ-1a) alone. Previously unreported secondary and tertiary magnetic resonance imaging (MRI) measures are presented here. Patients received natalizumab 300 mg (n=589) or placebo (n=582) intravenously every 4 weeks plus IFNβ-1a 30 μg intramuscularly once weekly. Annual MRI scans allowed comparison of a range of MRI end points versus baseline. Over 2 years, 67% of patients receiving natalizumab plus IFNβ-1a remained free of newor enlarging T2- lesions compared with 30% of patients receiving IFNβ-1a alone. The mean change from baseline in T2 lesion volume over 2 years decreased in patients receiving natalizumab plus IFNβ-1a and increased in those receiving IFNβ-1a alone (–277.5 mm3 versus 525.6 mm3; pb0.001). Compared with IFNβ-1a alone, add-on natalizumab therapy resulted in a smaller increase in mean T1-hypointense lesion volume after 2 years (1821.3 mm3 versus 2210.5mm3; pb0.001), a smaller mean number of new T1-hypointense lesions over 2 years (2.3 versus 4.1; pb0.001), and a slower rate of brain atrophy during the second year of therapy (–0.31% versus –0.40%; p=0.020). Natalizumab add-on therapy reduced gadolinium-enhancing, T1-hypointense, and T2 MRI lesion activity and slowed brain atrophy progression in patients with relapsing MS who experienced disease activity despite treatment with IFNβ-1a alon

The incidence and significance of anti-natalizumab antibodies - Results from AFFIRM and SENTINEL

Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab