SciCombinator

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Concept: Interferon beta-1b

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Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.

Concepts: Immune system, Antibody, Cytokine, Natural killer cell, Interferon, Multiple sclerosis, Interferon beta-1a, Interferon beta-1b

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OBJECTIVE: A double-blind, randomized, controlled study to determine if combined use of interferon beta-1a (IFN) 30ug IM weekly and glatiramer acetate (GA) 20mg daily is more efficacious than either agent alone in relapsing-remitting multiple sclerosis (RRMS). METHODS: 1008 participants were randomized and followed until the last participant enrolled completed 3 yrs. The primary endpoint was reduction in annualized relapse rate utilizing a strict definition of relapse. Secondary outcomes included time to confirmed disability, Multiple Sclerosis Functional Composite (MSFC) score and MRI metrics. RESULTS: Combination IFN + GA was not superior to the better of the single agents (GA) in risk of relapse. Both the combination therapy and GA were significantly better than IFN in reducing the risk of relapse. The Combination was not better than either agent alone in lessening confirmed EDSS progression or change in MSFC over 36 months. The combination was superior to either agent alone in reducing new lesion activity and accumulation of total lesion volumes. In a post hoc analysis, combination therapy resulted in a higher proportion of participants attaining disease activity free status (DAFS) compared to either single arm; driven by the MRI results. INTERPRETATION: Combining the two most commonly prescribed therapies for MS did not produce a significant clinical benefit over three years. An effect was seen on some MRI metrics. In a test of comparative efficacy, GA was superior to IFN in reducing the risk of exacerbation. The extension phase for CombiRx will address if the observed differences in MRI and DAFS findings predict later clinical differences. ANN NEUROL 2010.

Concepts: Randomized controlled trial, Effectiveness, Interferon, Multiple sclerosis, Interferon beta-1a, Interferon beta-1b, Glatiramer acetate, Immunostimulants

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To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS).

Concepts: Clinical trial, Interferon, Multiple sclerosis, Interferon beta-1a, Interferon beta-1b

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Subcutaneous pegylated interferon (peginterferon) beta-1a is being developed for treatment of relapsing multiple sclerosis, with less frequent dosing than currently available first-line injectable treatments. We assessed the safety and efficacy of peginterferon beta-1a after 48 weeks of treatment in the placebo-controlled phase of the ADVANCE trial, a study of patients with relapsing-remitting multiple sclerosis.

Concepts: Pharmacology, Interferon, Multiple sclerosis, Hepatitis B, Polyethylene glycol, Interferon beta-1a, Interferon beta-1b, Treatment of multiple sclerosis

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The appearance of neutralizing antibodies (NAbs) has significant clinical and regulatory consequences for interferons in patients with multiple sclerosis (MS). In a double blind, randomized clinical trial, 84 patients with relapsing remitting MS were enrolled in a 24 months study period. Patients were randomly assigned into two groups receiving 30 mcg weekly intramuscular injections of either Avonex® (Biogen Idec, USA; 42 patients) or CinnoVex® (CinnaGen Co, Iran; 42 patients). NAb titer was drawn for all patients every 6 months and assayed using cytopathic effect assay (CPE) method in Tehran, Iran. To validate the measure done in the Iranian lab, 45 sera with adequate volume and proper storing condition were selected and sent to be rechecked using luciferase reporter gene assay (LA) method for verification in 2 phases in Vancouver, Canada. The cut-off point of 20 TRU was considered for positivity. The two labs found the same three samples to be positive (2 samples from patients received Avonex and 1 received CinnoVex) and 42 to be negative. They had the following values using the Kawade formula as recommended by international standards; 2238, 89 and 302 (TRu/ ml) using CPE assay versus 2464, 290 and 169 (TRu/ ml) using LA method. As similar results were obtained from CinnoVex or Avonex in our study, we suggest that both medications will have a similar immunogenetic profile.

Concepts: Clinical trial, Interferon, Multiple sclerosis, Intramuscular injection, Interferon beta-1a, Interferon beta-1b, Biogen Idec, CinnoVex

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Peginterferon beta-1a (Plegridy™), an interferon beta-1a conjugated to a methoxy polyethylene glycol (PEG) molecule, is available in the EU and the USA for the treatment of adults with relapsing-remitting multiple sclerosis (RRMS). In a 96-week multinational, phase III study in this patient population (ADVANCE), subcutaneous peginterferon beta-1a 125 µg every 2 weeks significantly reduced the adjusted annualized relapse rate over 48 weeks, compared with placebo, corresponding to 36 % fewer relapses per patient-year. Significant reductions versus placebo were also observed in the risk of relapse and disability progression, the number of new or newly enlarging T2-weighted hyperintense lesions, and various other magnetic resonance imaging endpoints. The efficacy of peginterferon beta-1a was sustained over 96 weeks, with preliminary data from the first year of an ongoing 2-year extension of ADVANCE indicating continued benefit longer-term. In ADVANCE, peginterferon beta-1a had an acceptable tolerability profile that was consistent with that of established interferon beta treatments. Adverse events were generally mild or moderate in severity, with injection-site erythema and influenza-like illness reported most commonly. Amongst other adverse events of special interest, peginterferon beta-1a was not associated with an increased risk of autoimmune disorders, depression/suicidal ideation, infections or seizures. In the absence of head-to-head studies, definitive conclusions on the comparative efficacy and tolerability of peginterferon beta-1a versus existing therapies are not yet possible. Although final data from the extension of ADVANCE are awaited, current evidence suggests subcutaneous peginterferon beta-1a every 2 weeks extends the treatment options currently available for adults with RRMS, with the dosing regimen imparting potential compliance advantages over non-PEGylated interferon beta formulations that require more frequent administration.

Concepts: Cytokines, Magnetic resonance imaging, Interferon, Multiple sclerosis, Relapse, Interferon beta-1a, Interferon beta-1b, Interferon type I

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An exploratory study of the relationship between cumulative exposure to subcutaneous (sc) interferon (IFN) β-1a treatment and other possible prognostic factors with long-term clinical outcomes in relapsing-remitting multiple sclerosis (RRMS).

Concepts: Interferon, Multiple sclerosis, Interferon beta-1a, Interferon beta-1b

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To examine the long-term impact of early treatment initiation of interferon beta-1b (IFNB1b, Betaferon/Betaseron) in patients with a first event suggestive of multiple sclerosis (MS).

Concepts: Interferon, Multiple sclerosis, Interferon beta-1a, Interferon beta-1b

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Early treatment following a first clinical demyelinating event (FCDE) delays further disease activity in patients with multiple sclerosis (MS). This study determined the effects of early versus delayed treatment (DT) with subcutaneous interferon (sc IFN) β-1a 44 μg in patients with an FCDE up to 60 months postrandomisation.

Concepts: Interferon, Multiple sclerosis, Delay, Interferon beta-1a, Interferon beta-1b

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Low serum 25-hydroxyvitamin D (25[OH]D) levels are associated with an increased risk of multiple sclerosis (MS) as well as with increased disease activity and rate of progression in clinically isolated syndromes and early MS.

Concepts: Vitamin D, Cancer, Vitamin, Interferon, Multiple sclerosis, Vitamins, Interferon beta-1a, Interferon beta-1b