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.
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- "Probably the most common reasons supporting the selection of IFN beta-1b are its long history of safe use and the efficacy of high-dose high-frequency therapy. Disease stage may also be a consideration given the evidence that IFN beta-1b delayed conversion to CDMS among patients experiencing CIS; it is also a treatment option to consider later in the disease course, in relapsing SPMS, given the reduction in relapse rates observed during phase 3 trials [8, 36], and the lower risk of disability progression subsequently determined across these trials . IFN beta-1b can be used as a de-escalation option to reduce the likelihood of certain side-effects associated with long-term use of more aggressive therapies although further studies are warranted . "
ABSTRACT: Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and intravenous alemtuzumab] indicated for first-line use in relapsing–remitting MS. Here we review the clinical trial and follow-up data for IFN beta-1b and discuss factors that clinicians may consider when selecting this treatment, both at first line in early MS, and later in the disease course. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0149-1) contains supplementary material, which is available to authorized users.Advances in Therapy 09/2014; 31(9). DOI:10.1007/s12325-014-0149-1 · 2.44 Impact Factor
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- "The worsened patient group was characterised by a 24-month increase in the EDSS score by one point if the baseline EDSS score was less than 5.5, or an increase in the EDSS score by half a point if the baseline EDSS score was between 5.5 and 7.0. All other patients were defined as non-worsened [16,17]. "
ABSTRACT: Responsiveness, defined as the ability to detect a meaningful change, is a core psychometric property of an instrument measuring quality of life (QoL) rarely reported in multiple sclerosis (MS) studies. To assess the responsiveness of the Multiple Sclerosis International Quality of Life (MusiQoL) questionnaire to change in disability over 24 months, defined by change in the Expanded Disability Status Scale (EDSS) score. Patients with MS were enrolled into a multicenter, longitudinal observational study. QoL was assessed using both the MusiQoL and the 36-Item Short-Form (SF-36) instruments at baseline and every 6 months thereafter up to month 24; neurological assessments, including EDSS score, were performed at each evaluation. The 24-month EDSS was available for 524 patients. In the 107 worsened patients, two specific dimensions of MusiQoL, the sentimental and sexual life and the relationships with health care system dimensions, and 'physical' scores of SF-36 showed responsiveness. Whereas specific dimensions of MusiQoL identified EDSS changes, the MusiQoL index did not detect disability changes in worsened MS patients in a 24-month observational study. Future responsiveness validation studies should include longer follow-up and more representative samples.Health and Quality of Life Outcomes 07/2013; 11(1):127. DOI:10.1186/1477-7525-11-127 · 2.10 Impact Factor
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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