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interferon beta 1a [keywords]
- Treatment of mood disorders in multiple sclerosis. [Journal Article]
- Curr Treat Options Neurol 2015 Jan; 17(1):323.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with a significant comorbidity with depressive disorders. Prevalence rates for major depressive disorder (MDD) range from 36 % to 54 % and the rate is around 22 % for adjustment disorders. Selective serotonin reuptake inhibitors (SSRIs) are considered well-tolerated first-line treatment. Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are generally reserved for second-line use after SSRIs, because of sedating or anticholinergic side effects. SNRIs, with the exception of duloxetine, and combinations of newer antidepressants have failed to treat depression due to their side effects profile and frequent interaction with other drugs. Among SSRIs, sertraline is usually the first option, starting at 25 mg/day and increasing to 50 mg/day; and waiting a few weeks to assess drug effects before increasing the dose. The maximum is generally 200 mg/day in a single dose. Paroxetine is the second choice, starting at 10 mg/day for the first 5 days, and then at 20 mg/day thereafter. The maximum dose is about 50 mg/day in a single dose. Fluvoxamine is used at 100-200 mg/day, starting with 25 mg/day, and increasing 25 mg/day every 5 days until 200 mg/day is reached. We should take into account increasing blood level amounts of MS treatments (corticosteroids and cyclophosphamide) with fluvoxamine. With duloxetine, doses will be at 60-120 mg/day. The initial dose for depression is 40 mg/day in two doses; it can increase to 60 mg/day in one to two doses if necessary. The maximum dose is generally 120 mg/day. Duloxetine may increase liver problems through interaction with these MS treatments: teriflunomide, interferon beta-1a, and interferon beta-1b. Considering psychotherapy, only cognitive behavior therapy and mindfulness-based interventions have shown efficacy in improving depression disorders in MS. A comprehensive treatment for depression should include pharmacotherapy and psychotherapy.
- MRI correlates of disability progression in patients with CIS over 48 months. [Journal Article]
- Neuroimage Clin 2014.:312-9.
Gray matter (GM) and white matter (WM) pathology has an important role in disease progression of multiple sclerosis (MS).To investigate the association between the development of GM and WM pathology and clinical disease progression in patients with clinically isolated syndrome (CIS).This prospective, observational, 48-month follow-up study examined 210 CIS patients treated with 30 µg of intramuscular interferon beta-1a once a week. MRI and clinical assessments were performed at baseline, 6, 12, 24, 36 and 48 months. Associations between clinical worsening [24-weeks sustained disability progression (SDP) and occurrence of a second clinical attack] and longitudinal changes in lesion accumulation and brain atrophy progression were investigated by a mixed-effect model analysis after correction for multiple comparisons.SDP was observed in 32 (15.2%) CIS patients, while 146 (69.5%) were stable and 32 (15.2%) showed sustained disability improvement. 112 CIS patients (53.3%) developed clinically definite MS (CDMS). CIS patients who developed SDP showed increased lateral ventricle volume (p < .001), and decreased GM (p = .011) and cortical (p = .001) volumes compared to patients who remained stable or improved in disability. Converters to CDMS showed an increased rate of accumulation of number of new/enlarging T2 lesions (p < .001), decreased whole brain (p = .007) and increased lateral ventricle (p = .025) volumes.Development of GM pathology and LVV enlargement are associated with SDP. Conversion to CDMS in patients with CIS over 48 months is dependent on the accumulation of new lesions, LVV enlargement and whole brain atrophy progression.
- Does interferon Beta-1a impact pure-tone hearing sensitivity among individuals with multiple sclerosis? [Journal Article]
- J Neurosci Nurs 2014 Dec; 46(6):351-60.
Previous studies reported that particular types of interferon medications might contribute to hearing loss in some patients. The package insert included in the original Food and Drug Administration application for intramuscular interferon beta-1a (Avonex) stated that some patients in the treatment group reported decreased hearing sensitivity.The purpose of the present investigation was to assess if individuals with multiple sclerosis (MS) taking intramuscular interferon beta-1a have significantly poorer hearing thresholds than those not currently using any disease-modifying therapies.This was a secondary analysis of data collected as part of two larger studies evaluating auditory function in patients with MS. The goal of this analysis was to determine if users of interferon beta-1a do not have significantly worse hearing thresholds than nonusers of disease-modifying therapies, after adjusting for potential confounders. A linear mixed model was fit to the audiometric thresholds of our subjects. This model included interferon beta-1a use, MS disease subtype, gender, test frequency, age, disease duration (number of years), and the Expanded Disability Status Scale score.With all subjects included, there is insufficient evidence to say that intramuscular interferon-beta 1a is not ototoxic (in relation to nonuse of a disease-modifying therapy) at all frequencies tested except 3000 and 6000 Hz. After removing two influential subjects, the results indicated that there is statistical support for no ototoxic effect of intramuscular interferon beta-1a at test frequencies from 250 to 6000 Hz. There is insufficient evidence, however, to rule out an ototoxic effect at 8000 Hz. Future studies should further evaluate the effect of interferon on auditory function in patients with MS. Neuroscience nurses should monitor their patients' hearing throughout the course of treatment.
- A randomized controlled phase II trial of riluzole in early multiple sclerosis. [Journal Article]
- Ann Clin Transl Neurol 2014 May; 1(5):340-7.
We evaluated the effect of riluzole versus placebo added to weekly IM interferon beta-1a in early multiple sclerosis (MS).This is a randomized (1:1), double-blind, placebo-controlled trial of riluzole 50 mg twice daily in subjects with MS onset less than 1 year prior. Trial participation was up to 3 years. The primary endpoint was change in percent brain volume change. Secondary endpoints included changes in normalized gray and normal-appearing white matter volumes, retinal nerve fiber layer thickness (RNFL), MS Functional Composite and Symbol Digit Modalities Test scores. Mixed model regression analysis was used to compare the changes over time between groups.Forty-three subjects were randomized to study drug (22 riluzole, 21 placebo). Baseline characteristics were overall similar between groups except for older age (P = 0.042), higher normalized cerebrospinal fluid volume (P = 0.050), lower normalized gray matter volume (P = 0.14), and thinner RNFL (P = 0.043) in the riluzole group. In the primary analysis, percent brain volume change in the placebo group decreased at a rate of 0.49% per year whereas the riluzole group decreased by 0.86% per year (0.37% more per year; 95% CI -0.78, 0.024; P = 0.065). Although age did not influence the rate of brain volume decline, the difference between groups was attenuated after adjustment for baseline normalized gray matter and lesion volume (0.26% more per year in riluzole group; 95% CI -0.057, 0.014; P = 0.22). Analyses of secondary outcomes showed no differences between groups.This trial provides class 1 evidence that riluzole treatment does not meaningfully reduce brain atrophy progression in early MS.
- [Experience of using genfaxon for treating patients with relapsing-remitting multiple sclerosis in the Russian Federation]. [English Abstract, Journal Article]
- Zh Nevrol Psikhiatr Im S S Korsakova 2014; 114(8):39-45.
Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system. Nowadays some disease-modifying drugs (DMD) in the Russian Federation (RF) are biosimilars. Their full spectrum of tolerability and efficacy is to be determined. Here we present results of two retrospective-prospective studies on efficacy and safety of a biosimilar interferon beta-1a (genfaxon) in treatment of MS in the RF.determination of safety and efficacy profile of genfaxon in a routine neurological practice in the RF.Trials were performed in 18 MS centers in the RF. A total of 649 patients aged from 18 to 68 years with the EDSS score no more than 6.0 were treated with genfaxon for 12 months. The first group was comprised of 'naïve' patients without previous history of DMD administration. There were patients in the second group which have already received some of DMD. Statistical analysis was performed with the help of significance criteria (χ-square), t-criteria of Student for analysis of independent samplings.There were no serious adverse events during the period of the study. "Naïve" patients had significantly lower number of adverse events, than patients with previous history of DMD usage. Efficacy results were comparable with results published for the Rebif.Data, received from the studies show equal efficacy and tolerability of genfaxon compared with original DMD Rebif.
- Alemtuzumab: A new therapy for active relapsing-remitting multiple sclerosis. [REVIEW]
- Mult Scler 2014 Oct 24.
Alemtuzumab is a humanized monoclonal antibody directed against CD52 to deplete circulating T and B lymphocytes; lymphocyte depletion is followed by a distinctive pattern of T- and B-cell repopulation, changing the balance of the immune system. This review reports the efficacy and safety findings of the phase 2 CAMMS223 trial and the phase 3 CARE-MS I and II trials investigating alemtuzumab for the treatment of active relapsing-remitting MS. Alemtuzumab, administered intravenously, was shown to improve relapse rate versus subcutaneous interferon beta-1a in patients who were treatment-naive (CAMMS223 and CARE-MS I) or had relapsed on prior therapy (CARE-MS II), and to reduce sustained accumulation of disability (CAMMS223 and CARE-MS II). Important adverse events were infusion-associated reactions, serious infections and autoimmune events. A safety monitoring program allowed for early detection and management of autoimmune events. Recommendations for the monitoring of adverse events are made. Alemtuzumab's mechanism of action, pharmacodynamics and opportunities for future research are discussed.
- Ten-year follow-up of the 'minimal MRI lesion' subgroup from the original CHAMPS Multiple Sclerosis Prevention Trial. [JOURNAL ARTICLE]
- Mult Scler 2014 Oct 24.
Patients with clinically isolated syndrome (CIS) and characteristic magnetic resonance imaging (MRI) lesions are at high risk for multiple sclerosis (MS). However, patients with a minimal MRI lesion burden (a low T2-hyperintense [low T2] lesion count) may have borderline formal diagnostic criteria, presenting a clinical management challenge.Compare the 10-year disease progression of patients with low and higher T2 lesion counts treated over most intervals.CIS patients from the original CHAMPS MS trial were retrospectively assigned to low-T2 (first quartile; 2-8 lesions) or higher-T2 (second through fourth quartiles; ≥ 9 lesions) groups using baseline T2 lesion counts. The 5- and 10-year open-label extension of CHAMPS (CHAMPIONS) evaluated conversion to clinically definite MS (CDMS), MRI activity, relapses, and disability.The vast majority of patients showed new disease activity by MRI and/or clinical criteria at 10 years (low-T2 86%; higher-T2 98%). Fewer low-T2 than higher-T2 patients developed CDMS (40% vs. 63%; p = 0.013); low-T2 patients also had fewer new brain lesions, less brain volume loss, and less disability progression.CIS patients with low T2 lesion counts show continued disease activity. However, all assessments of disease progression over 10 years indicated a significantly less severe disease course for low-T2 patients.
- Associated Inosine to interferon: results of a clinical trial in multiple sclerosis. [JOURNAL ARTICLE]
- Acta Neurol Scand 2014 Oct 14.
Uric acid (UA) could act as a natural peroxynitrite scavenger with antioxidant properties. It has been proposed that hyperuricemia might protect against multiple sclerosis (MS).Patients with relapsing-remitting MS starting treatment with interferon beta-1a 44 µg sc 3/week were randomly assigned to receive either inosine 3 g/day or placebo in a double-blind manner. Follow-up was 12 months. Outcome measures were adverse events and UA laboratory results. Secondary end point was clinical and radiological activity of MS. Relapse rates, percentage of patients without relapses, and progression to secondary MS (SPMS) were assessed.Thirty six patients were included. Two patients in the inosine group showed UA serum level above 10 mg/ml, and symptoms derived from renal colic not leading to hospital admission. Ten additional patients had asymptomatic hyperuricemia (>7 mg). Efficacy parameters (clinical and radiological) were similar between groups. No patient progressed to SPMS CONCLUSIONS: Inosine administration was associated with hyperuricemia and renal colic with no additional effect on MS. We cannot conclude inosine is a safe and well-tolerated drug. Doses of around 2 g/day may be more appropriate for future trials.
- Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis. [JOURNAL ARTICLE]
- Eur J Neurol 2014 Oct 13.
Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported.CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced.One patient had a novel mutation, c.2562T>A; p.Asn854Lys, in the CSF1R gene. Her symptoms started at the age of 29 years with insidious onset of pyramidal weakness in the left leg. The cerebrospinal fluid examination showed four intrathecal immunoglobulin G bands. A magnetic resonance imaging scan performed 4 years after symptom onset demonstrated patchy deep WM lesions. She was diagnosed as having PPMS and treated with intramuscular interferon beta 1a. Due to slow disease progression, the development of memory decline and cerebellar signs, she was given subcutaneous interferon beta 1a without any benefit. The updated pedigree indicated that five siblings also had the CSF1R gene mutation; one was diagnosed with PPMS. Six more distant relatives also had a neurological disorder; four were clinically diagnosed with PPMS.Our study indicates that a chronic course of HDLS may mimic PPMS. Genetic testing for CSF1R gene mutations in PPMS cases with a positive family history of neurological disorders may establish the diagnosis of HDLS.
- Late relapse of non-seminomatous testicular cancer during treatment of multiple sclerosis with interferon β-1a: A case report. [JOURNAL ARTICLE]
- Oncol Lett 2014 Nov; 8(5):2179-2182.
Germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes. The present study reports a patient diagnosed with non-seminomatous testicular cancer, stage IB, with a good risk prediction according to the International Germ Cell Cancer Collaborative Group classification. The patient received chemotherapy with bleomycin, etoposide and cisplatin, and achieved complete remission. Eleven years later, while receiving treatment with interferon β-1a for multiple sclerosis, the patient developed a relapse of the original cancer in the lungs and lymph nodes. The majority of GCTs relapse within the first two years of treatment, while 2-4% of patients can present with late relapses. There is no clear established association between multiple sclerosis and testicular cancer; we present the hypothesis that the inmunosupressor treatment that was administered for the multiple sclerosis promoted the cancer relapse.