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interferon beta 1a [keywords]
- Interferon Beta-1a treatment in HTLV-1-associated myelopathy/tropical spastic paraparesis: a case report. [Journal Article]
- Rev Inst Med Trop Sao Paulo 2014 Sep; 56(5):443-5.
Here a young patient (< 21 years of age) with a history of infective dermatitis is described. The patient was diagnosed with myelopathy associated with HTLV-1/tropical spastic paraparesis and treated with interferon beta-1a. The disease was clinically established as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and laboratory tests confirmed the presence of antibodies to HTLV-1 in the cerebrospinal fluid (CSF). Mumps, cytomegalovirus, Epstein-Barr virus, schistosomiasis, herpes virus 1 and 2, rubella, measles, varicella-zoster toxoplasmosis, hepatitis, HIV, and syphilis were excluded by serology. The patient was diagnosed with neurogenic bladder and presented with nocturia, urinary urgency, paresthesia of the lower left limb, a marked reduction of muscle strength in the lower limbs, and a slight reduction in upper limb strength. During the fourth week of treatment with interferon beta-1a, urinary urgency and paresthesia disappeared and clinical motor skills improved.
- Pharmacokinetics, pharmacodynamics, and safety of peginterferon beta-1a in subjects with normal or impaired renal function. [JOURNAL ARTICLE]
- J Clin Pharmacol 2014 Sep 4.
Peginterferon beta-1a was efficacious in a Phase 3 relapsing multiple sclerosis trial, and its safety profile was consistent with other beta interferons. This study evaluated the impact of renal impairment on the pharmacokinetics and pharmacodynamics (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) of peginterferon beta-1a following a single subcutaneous dose at 63 μg (n = 5) or 125 μg (n = 30). The results showed a fractional increase in area-under-the-concentration-time curve (AUC [30-53%]) and peak serum concentration (Cmax [26-42%]) in subjects with mild, moderate, and severe renal impairment, versus healthy subjects; AUC and Cmax were similar for healthy subjects and end-stage-renal-disease patients receiving hemodialysis. Pharmacokinetic simulation showed that the steady state concentration overlapped in the majority of healthy subjects and subjects with severe renal impairment. Neopterin baseline, peak concentration, and AUC increased as renal function decreased. Peginterferon beta-1a was well tolerated in all groups. These results do not warrant peginterferon beta-1a dose adjustment in subjects with renal impairment.
- The Clinical Meaning of Walking Speed as Measured by the Timed 25-Foot Walk in Patients With Multiple Sclerosis. [JOURNAL ARTICLE]
- JAMA Neurol 2014 Sep 1.
Walking impairment, a common clinical manifestation of multiple sclerosis (MS), is often measured in clinical practice and clinical trials using the Timed 25-Foot Walk (T25-FW).To evaluate the relationship between walking speed measured by the T25-FW and the Physical Component Summary (PCS) score of the 36-Item Short Form Health Survey (SF-36) to better understand the clinical meaning of T25-FW walking speed in MS.We retrospectively analyzed data from 3 clinical trials (Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis [AFFIRM], Safety and Efficacy of Natalizumab in Combination With Interferon Beta-1a in Patients With Relapsing-Remitting Multiple Sclerosis [SENTINEL], and International MS Secondary Progressive Avonex Controlled Trial [IMPACT]) that included T25-FW and SF-36 scores as outcomes in patients with MS. Patients had secondary-progressive MS and an Expanded Disability Status Scale score of 3.5 to 6.5 or relapsing-remitting MS and an Expanded Disability Status Scale score of 0 to 5.0.We used Spearman rank correlation and Pearson product moment correlation (r ) and descriptive statistics to evaluate retrospectively the relationship between the SF-36 PCS score and T25-FW walking speed at baseline and the 2-year changes from baseline.Among all 2549 patients from the 3 trials, walking speed and SF-36 PCS score at baseline were significantly correlated (n = 2333; r = 0.48; P < .001). In placebo-treated patients at 2 years, the percentage of change from baseline in walking speed was significantly correlated with the change from baseline in SF-36 PCS score (r = 0.35; P < .001). Significant correlations between the change in SF-36 PCS scores and the percentage of change in walking speed at 2 years also were observed in groups receiving active treatment (r, 0.13-0.28; P ≤ .005). Among placebo-treated patients, 27.5% had a clinically meaningful worsening (≥5-point decrease) in SF-36 PCS scores during the 2 years. Walking speed declined by 21.8% in these patients after 2 years, but only by 5.4% in those without worsening of SF-36 PCS scores.In patients with MS, walking speed measured using the T25-FW correlated with SF-36 PCS scores such that a decline in walking speed of 20% to 25% corresponded to a clinically meaningful worsening of SF-36 PCS scores. A 20% to 25% decline in walking speed may be a clinically meaningful threshold for defining worsening using the T25-FW in MS clinical trials and for monitoring patients in clinical settings.
- 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 physicochemical and biological characterization by means of electrospray ionization-mass spectrometry, sialic acid content, thermal denaturation and various in vitro bioassays (antiproliferative, 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.