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interferon beta 1a [keywords]
- In vitro Biological Characterization of IFN-β-1a major Glycoforms. [JOURNAL ARTICLE]
- Glycobiology 2014 Aug 11.
Recombinant Human Interferon β-1a (IFN-β-1a) is extensively used as the first-line treatment of relapsing forms of Multiple Sclerosis. Its glycosylation is recognized as having a complex impact on a wide range of molecule characteristics and functions. The present study reports the enrichment of IFN-β-1a glycoforms and their physico-chemical and biological characterization by means of mass spectrometry (ESI-MS), sialic acid content, thermal denaturation and various in vitro bioassays (anti-proliferative, antiviral, immunomodulatory, and reporter gene assay). The glycoforms were fractionated by means of cation-exchange chromatography using recombinant IFN-β-1a derived from Chinese Hamster Ovary cell culture as starting material. The obtained fractions contained bi- and higher-antennarity glycans as described in the European Pharmacopoeia monograph (Nr. 1639E, Interferon beta 1a concentrated solution). The in vitro bioassay responses revealed a correlation mainly with the glycan antennarity. It is therefore suggested that all glycoforms are having biological activity and play a role in modulating the overall IFN-β biological activity with higher-antennarity glycoforms being able to better sustain IFN-β-1a bioactivity over time. These data indicate the role of IFN-β-1a glycosylation in-vivo and sheds new light on the role of the glycosylation heterogeneity, in particular with regard to antennarity, on biological properties of glycoproteins.
- Fingolimod: A Review of Its Use in Relapsing-Remitting Multiple Sclerosis. [JOURNAL ARTICLE]
- Drugs 2014 Jul 26.
Fingolimod (Gilenya(®)) is an orally administered disease modifying agent (DMA) for use in relapsing-remitting multiple sclerosis (RRMS). In placebo-controlled trials in patients with RRMS with active disease, fingolimod 0.5 mg/day significantly reduced the annualized relapse rate (ARR) by approximately one-half over 2-year trial periods. It also significantly increased the proportion of patients with no disability progression, reduced deterioration from baseline in the Extended Disability Status Scale score and reduced MRI markers of disease progression (new/newly enlarging brain lesions and percentage change in brain volume). In a 12-month, comparison with intramuscular interferon β-1a (IFNβ- 1a) 30 μg/week, the ARR in fingolimod 0.5 mg/day recipients was significantly lower than in IFNβ-1a recipients by one-half; fingolimod recipients also had significantly lower MRI markers of disease progression. In extensions to the pivotal clinical trials, fingolimod exposure for up to 4 years was associated with low relapse rates and continuing benefits in terms of disability and disease progression. In clinical trials, adverse events in fingolimod recipients were generally mild to moderate in severity. In the pivotal placebo-controlled trial, serious adverse events occurred in similar proportions of fingolimod 0.5 mg/day and placebo recipients. First-dose bradycardia and atrioventricular block, which are generally asymptomatic, were clinically important adverse events associated with fingolimod in placebo-controlled trials. The risk for serious cardiovascular adverse events at the approved fingolimod dosage appears to be low in patients without pre-existing cardiac conditions. Fingolimod is an efficacious therapy for RRMS that reduces relapses, disability progression, new brain lesions and loss of brain volume. It has an acceptable tolerability profile and provides a useful alternative treatment in patients with RRMS who have responded poorly to other DMAs.
- Treatment satisfaction in multiple sclerosis. [Journal Article]
- Int J MS Care 2014; 16(2):68-75.
Disease-modifying therapies (DMTs) for the treatment of multiple sclerosis (MS) are associated with inconvenient methods of administration, significant side effects, and low adherence rates. This study was undertaken to compare treatment satisfaction in MS patients treated with interferon beta-1a intramuscular (IFNβ-1a IM), interferon beta-1a subcutaneous (IFNβ-1a SC), glatiramer acetate (GA), and natalizumab (NTZ), and to examine the associations between treatment satisfaction ratings and adherence to therapy.Two hundred twenty-six treated MS patients completed the Treatment Satisfaction Questionnaire for Medicine. Multivariable models were used to compare treatment satisfaction across groups.There were no statistically significant differences in overall treatment satisfaction. The NTZ group reported greater satisfaction with the ability of the medication to treat or prevent MS than the IFNβ-1a IM group. The NTZ group also reported higher overall convenience scores than the IFNβ-1a IM group and greater satisfaction with ease of use of the medication than the interferon and GA groups. Patients in the IFNβ-1a IM group reported less satisfaction with ease of planning when to use the medication than those in the other groups. Convenience was associated with adherence in IFNβ-1a SC- and GA-treated patients, with lower convenience scores associated with lower adherence.These results may be useful to MS patients and health-care providers facing decisions about DMT use.
- PREDICTIVE VALUE OF EARLY SERUM CYTOKINE CHANGES ON LONG-TERM INTERFERON-BETA 1A EFFICACY IN MULTIPLE SCLEROSIS. [JOURNAL ARTICLE]
- Int J Neurosci 2014 Jul 15.:1-11.
ABSTRACT Background: In a previous study, we had evaluated short-term effects of interferon beta-1a (IFNB-1a) 44 μg s.c. three times per week treatment on serum levels of IFN-gamma (IFNG), IL-23, IL-17, IL-10, IL-9, IL-4 and TGF-beta (TGFB) and found a reduction only in IL-17 and IL-23 levels after 2 months of treatment. Methods: Using the same multiple sclerosis (MS) cohort, we assessed the predictive value of early cytokine level changes (difference between 2(nd) month and baseline levels as measured by ELISA) on the efficacy of long-term IFNB-1a treatment. Results: The alteration in IFNG levels of patients without any relapse was statistically lower than that of patients having one or more relapses (p = 0.019, Student's t test). When patients with or without expanded disability severity scale (EDSS) progression were compared, none of the cytokine level changes showed a significant difference between groups. IL-17 and IL-23 level changes did not predict relapse and EDSS progression in IFNB-1a treated MS patients. Conclusion: Our results show that the predictive power of early IFNG measurement on relapse occurrence may potentially extend a time span of several years.
- Melatonin Acts as Antioxidant and Improves Sleep in MS Patients. [JOURNAL ARTICLE]
- Neurochem Res 2014 Jun 30.
The relationship between the prevalence of multiple sclerosis (MS) and sunlight's ultraviolet radiation was proved. Oxidative stress plays a role in the pathogenic traits of MS. Melatonin possesses antioxidative properties and regulates circadian rhythms. Sleep disturbances in MS patients are common and contribute to daytime fatigue. The aim of study was to evaluate 5 mg daily melatonin supplementation over 90 days on serum total oxidant status (TOS), total antioxidant capacity (TAC) and its influence on sleep quality and depression level of MS patients. A case-control prospective study was performed on 102 MS patients and 20 controls matched for age and sex. The Kurtzke's Expanded Disability Status Scale, magnetic resonance imaging examinations, Athens Insomnia Scale (AIS), Beck Depression Inventory questionnaires were completed. Serum TOS and TAC levels were measured. We observed higher serum levels of TOS in all MS groups, while after melatonin treatment the TOS levels significantly decreased. The TAC level was significantly lower only in mitoxantrone-treated group and it increased after melatonin supplementation. A strong positive correlation between T1Gd(+) number lesions and TAC level in interferon-beta-1A group was observed. AIS group mean score above 6 defining insomnia were observed in interferon-beta-1B-group, glatiramer acetate-group and mitoxantrone-group: 6.62 ± 2.88, 8.45 ± 2.07, 11.1 ± 3.25, respectively. After melatonin treatment the AIS mean scores decrease in glatiramer acetate-group and mitoxantrone-group achieving 5.25 ± 1.14 and 7.08 ± 2.39, respectively (p < 0.05). Finding from our study suggest that melatonin can act as an antioxidant and improves reduced sleep quality in MS patients.
- An observational, retrospective, UK and Ireland audit of patient adherence to subcutaneous interferon beta-1a injections using the RebiSmart(®) injection device. [Journal Article]
- Patient Prefer Adherence 2014.:843-51.
Poor adherence to disease-modifying drugs is associated with an increased risk of relapse in patients with multiple sclerosis. However, adherence is difficult to assess objectively. RebiSmart(®) (Merck Serono SA, Geneva, Switzerland), a device for subcutaneous (sc) injection of interferon (IFN) β-1a, features an electronic injection log that can assist in objective monitoring of adherence.To assess adherence to sc IFN β-1a injections using data from RebiSmart(®).This was a single-group, observational, retrospective audit. Adherence data were collected from patients with relapsing multiple sclerosis in the United Kingdom and Ireland who had been prescribed sc IFN β-1a and had been using RebiSmart(®) for a minimum of 24 months.In total, 225 patients were included in the full analysis set; 72% were in the United Kingdom, and 28% were in Ireland. Overall, the mean age was 44.1 years, and 73% were women. Patients received sc IFN β-1a 44 µg (68%) or 22 µg (32%) three times per week. Mean adherence over the course of 24 months was 95.0% (median, 99.4%), and similar values were observed across all periods. The proportion of patients with 80% or higher adherence was 92.0% at 12 months and 91.1% at 24 months.High adherence to sc IFN β-1a was observed across all patient groups using RebiSmart(®), according to 2-year treatment adherence data. This may be partly attributed to the expert support patients received, supplemented by routine and regular contact from the MySupport patient-support program, as well as the self-motivation of patients who persisted with treatment for 2 or more years.
- Enhanced patient support services improve patient persistence with multiple sclerosis treatment. [Journal Article]
- Patient Prefer Adherence 2014.:805-11.
Subcutaneous interferon beta-1a (sc IFN β-1a) therapy (44 µg or 22 µg, three times weekly) improves relapse rates and disability progression in patients with relapsing multiple sclerosis (MS). While early treatment with disease-modifying drugs may maximize therapeutic benefit, patients with low adherence or long treatment gaps are at increased risk of relapse. MySupport is an industry-sponsored program that provides support to patients with MS who have been prescribed sc IFN β-1a in the UK or Republic of Ireland (ROI), via telephone and text messaging, website access, and (in some cases) face-to-face support from a dedicated MySupport Nurse. The aim of this audit was to assess if the MySupport program in the ROI could improve persistence to sc IFN β-1a therapy.Anonymized data were supplied retrospectively from the MySupport program, for ROI patients who were registered in January 2010 to receive sc IFN β-1a three times weekly. Patients were recorded as "new" at their first drug delivery; "active", if they continued to receive scheduled deliveries; "interrupted", if their medication delivery was halted; or "stopped", if no deliveries were made for 12 months. The number of "active" patients was recorded monthly for 24 months. Results were compared with data from UK patients with MS, who were receiving National Health Service (NHS) support only, or this support plus MySupport.A greater proportion of ROI patients receiving MySupport (compared against UK patients receiving NHS support only) were on treatment at 12 months (87.8% versus 79.3%) and at 24 months (76.2% versus 61.8%). The odds of being on treatment were significantly greater, at all time points, for ROI patients receiving MySupport, versus UK patients receiving NHS support only (P<0.0001).A personalized support program, utilizing one-to-one nursing support and additional support materials, can increase the probability of patients with MS remaining on disease-modifying drug treatment.
- Efficacy and safety of subcutaneous interferon-β-1a in patients with a first demyelinating event and early multiple sclerosis. [JOURNAL ARTICLE]
- Expert Opin Biol Ther 2014 Jun 26.:1-8.
Introduction: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Evidence suggests that MS should be treated as early as possible in order to maximize the benefit of treatment. Areas covered: This review details current understanding about the treatment of relapsing-remitting MS (RRMS). The pharmacological and clinical data on the use of subcutaneous (s.c.) interferon β-1a (IFN-β-1a) as a therapeutic option for RRMS are covered, with a focus on the importance of treating patients with MS as early as possible in the course of the disease, in order to delay permanent axonal damage that is responsible for the signs and symptoms of disease progression. Expert opinion: There is a wealth of data on the treatment of RRMS with s.c. IFN-β-1a indicating that patients treated during the early inflammatory stages of the disease have significantly improved short-term outcomes compared with patients who commence treatment late. It remains to be determined whether the short-term effects of early treatment will translate into long-lasting benefits, although it is hoped that ongoing research will help to answer this question.
- Longitudinal MRI and neuropsychological assessment of patients with clinically isolated syndrome. [JOURNAL ARTICLE]
- J Neurol 2014 Jun 22.
Cognitive impairment (CI) may occur in clinically isolated syndrome (CIS) patients. While the relationship between CI and magnetic resonance imaging (MRI) has been investigated extensively in multiple sclerosis (MS), MRI correlates of CI in CIS patients are unknown. To investigate the evolution of CI and to determine brain MRI structural correlates associated with CI in CIS patients. This prospective 24-month observational study examined 81 CIS patients treated with 30 µg of intramuscular interferon beta 1a once a week. MRI acquisition and neuropsychological (NP) assessment were performed at baseline, 6, 12 and 24 months. Participants were tested with Czech-validated version of Minimal Assessment of Cognitive Function in MS battery and MRI measures of lesion activity and burden, and global, tissue-specific and regional brain atrophy were performed. Over 24 months, 36 CIS patients developed clinically definite MS (CDMS). CI was observed in 10 (12.3 %) CIS patients at baseline and at the 24 months follow-up. Eight CIS patients changed their CI status over the follow-up (four improved and four worsened). No significant difference in development of CI was detected between stable CIS patients and those who developed CDMS. In multivariate regression and mixed-effect model analyses, no significant relationship was found between NP and MRI parameters. The lack of significant relationship between MRI metrics and cognition in this group of CIS patients could be attributed to several factors including the cognitive reserve, effect of disease-modifying therapy and relatively short follow-up period.
- Alemtuzumab: The advantages and challenges of a novel therapy in MS. [REVIEW]
- Neurology 2014 Jun 11.
Our understanding of the pathogenesis of multiple sclerosis has increased considerably, leading to the development of novel therapeutic approaches and compounds. Several agents have undergone clinical testing and have recently received market authorization or are being evaluated for approval. Alemtuzumab is a humanized monoclonal antibody that rapidly depletes CD52+ cells of the lymphoid lineage from peripheral blood, but spares lymphoid precursor cells. Clinical efficacy and safety data from clinical phase II and III trials-all using interferon-β-1a as active comparator-are summarized and placed in perspective. This review further analyzes the differential reconstitution of T and B cells as a potential mode of action and the pathogenic link to treatment-emergent secondary autoimmune conditions. Given recent positive opinions by regulatory agencies, this new drug will be positioned for the treatment of active relapsing-remitting multiple sclerosis and enlarge our therapeutic armamentarium.