Interferon beta-1b in secondary progressive MS: A combined analysis of the two trials
ABSTRACT A European (EU) and a North American (NA) placebo-controlled study with interferon beta-1b (IFNB-1b) in secondary progressive multiple sclerosis (SPMS) showed divergent results with regard to their primary outcome of sustained Expanded Disability Status Scale (EDSS) progression, while effects were similar on relapse and MRI-related endpoints. Reasons for this discrepancy were explored in the combined dataset.
Baseline characteristics and variability in EDSS assessments were compared. Retrospective combined analyses for time to confirmed progression were performed to assess treatment effects overall and in subgroups defined by pre-study disease activity criteria and other key baseline variables.
The variance of EDSS measurements was 6.5% higher in the NA-SPMS study. The EU study included patients in an earlier phase of SPMS and with more active disease both pre-study (relapses, MRI) as well as on study (EDSS, relapses, and MRI variables as assessed in the placebo groups). The pooled analysis showed an overall risk reduction by about 20% in patients treated with 8 MIU (250 mcg) IFNB-1b for EDSS progression confirmed at 6 months (p = 0.008). Risk reduction by 30% to 40% was found for patients with at least one relapse or change in EDSS by >1 in the 2 years prior to study entry. No other consistent across-studies relation of clinical and MRI variables at baseline to potential treatment response was found.
Although post hoc, this combined analysis of the two large studies with IFNB-1b in secondary progressive multiple sclerosis suggests that both pronounced disability progression and continuing relapse activity might help in identifying those patients in the secondary progressive phase of the disease who are more likely to benefit from treatment.
- SourceAvailable from: Ludwig Kappos
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- "In contrast, another nonrandomized study of 1504 patients with RRMS showed that interferon ȕ-1a and -1b reduced disability progression (Trojano et al, 2007). Data for direct effects of interferon ȕ-1b on active SPMS are mixed, with 1 large-scale trial showing a significant reduction in disability progression and another showing no effect of the drug on progression in patients with more advanced disease (Kappos et al, 2004). Other correlational evidence suggests that interferon ȕ-1b can delay the time of onset of the progressive form of SPMS. "
ABSTRACT: Clinical trials have generated a wealth of data on the safety profile of interferon β-1b for patients with multiple sclerosis (MS). In general, interferon β-1b has not been associated with serious or life-threatening side effects during long-term treatment. Flu-like symptoms, injection site reactions, depression, and elevated liver transaminases were the most common adverse events in clinical trials. This review will discuss the rates of these and other common adverse events observed in 3 clinical trials of interferon β-1b: BENEFIT, BEYOND, and the 16-year Long-Term Follow-up (LTF) of the pivotal interferon β-1b trial in MS, as well as how these adverse events may influence patient and physician decision making when selecting a disease-modifying therapy. In addition, we will discuss the effects of interferon β-1b on mortality in the 16-year and 21-year LTF studies. Copyright © 2013 Elsevier B.V. All rights reserved.01/2013; 3(3). DOI:10.1016/j.msard.2013.11.005
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ABSTRACT: This review focuses on novel aspects of the pathogenesis and advances in the therapy of multiple sclerosis (MS). Recent observations suggest that early lesion development in MS may start in some forms with oligodendrocyte death and that inflammation appears as a secondary phenomenon only. The lack of sufficient remyelination in MS may be the result of a disturbed function of basic helix-loop-helix transcription factors. Clinically the identification of patients with a clinically isolated syndrome at high risk to develop clinically definite MS remains difficult; the predictive value of serum antibodies against myelin proteins remains controversial. The role of neutralizing antibodies in interferon therapy is discussed. New therapeutic approaches in MS are emerging. The existing view on the pathogenesis of MS is still changing. The original assumption that cell-mediated demyelination is the key event in lesion development dictating clinical disability is critically reviewed and alternative pathways have been suggested. Oligodendrocyte death, axonal loss, the role of CD8 T lymphocytes, T regulatory cells, and B lymphocytes have come into the focus of newly evolving concepts in MS pathogenesis. A deepened understanding of the immunopathogenesis of this disease translates into innovative therapeutic approaches, such as blockade of alpha4 integrins by a humanized monoclonal antibody. In various animal models cell-replacement strategies yield promising results; however, turning these findings into an effective therapy in MS patients has a long way to go.Current Opinion in Neurology 07/2005; 18(3):211-20. DOI:10.1097/01.wco.0000169735.60922.fb · 5.73 Impact Factor