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interferon beta 1a [keywords]
- 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.] [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. Aims. determination of safety and efficacy profile of genfaxon in a routine neurological practice in the RF. Materials and Methods. 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. Results. 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. Conclusions. 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.
- Title: Pharmacokinetics and Pharmacodynamics of Peginterferon Beta-1a in Patients with Relapsing-Remitting Multiple Sclerosis in the Randomised ADVANCE Study. [JOURNAL ARTICLE]
- Br J Clin Pharmacol 2014 Sep 29.
To evaluate the pharmacokinetics and pharmacodynamics of subcutaneous peginterferon beta-1a in patients with relapsing-remitting multiple sclerosis (RRMS) in the Phase 3 ADVANCE study (n=1512).During Year 1, patients were randomised (1:1:1) to placebo or peginterferon beta-1a 125 μg every 2 or 4 weeks. After Year 1, patients randomised to placebo were re-randomised to 125 μg peginterferon beta-1a administered every 2 weeks or every 4 weeks for Year 2. Patients randomised to peginterferon beta-1a in Year 1 remained on the same dosing regimen in Year 2. Intensive blood samples for pharmacokinetic and pharmacodynamic (neopterin elevation; a biomarker of pharmacological activity induced by interferon beta-1a) measurements were collected from 44 patients pre-dosing and at intervals over 240 hours post-dosing at Weeks 4 and 24. Sparse samples were collected from all patients after each dosing at Weeks 4, 12, 24, 56, and 84.The pharmacokinetic profile of peginterferon beta-1a did not change over time or between dosing regimens. No accumulation was observed. Peak serum concentrations were reached 1-1.5 days post-dosing, with a mono-phasic decline, and a median half-life of approximately 2-3 days. Dosing every 2 weeks provided approximately 2-fold greater monthly cumulative area-under-the-curve than every 4 weeks. Neopterin elevation was sustained for 10-14 days following each dose, indicating doubled cumulative duration of pharmacological activity for dosing every 2 weeks versus every 4 weeks.These pharmacokinetic/pharmacodynamic profiles potentially explain the enhanced efficacy of dosing every 2 weeks in patients with RRMS.
- Efficacy and Safety of Fingolimod in Hispanic Patients with Multiple Sclerosis: Pooled Clinical Trial Analyses. [JOURNAL ARTICLE]
- Adv Ther 2014 Sep 23.
The disease characteristics of multiple sclerosis (MS) appear to differ between Hispanic and Caucasian patients, with Hispanic patients having a younger age at onset, and a higher prevalence of optic nerve and spinal cord involvement. Fingolimod, the first-in-class oral sphingosine 1-phosphate receptor modulator approved for the treatment of relapsing MS, has been shown to significantly reduce annualized relapse rates (ARRs), lesion-based magnetic resonance imaging (MRI) activity, confirmed disability, and brain volume loss, compared with placebo or intramuscular interferon beta-1a (IFNβ-1a IM) in randomized, double-blind, controlled clinical studies. Here, the efficacy and safety profile of fingolimod in Hispanic patients was compared to that observed in the overall study populations.This was a post hoc analysis of relapses and safety data for Hispanic patients with relapsing-remitting MS (RRMS) randomized to receive daily fingolimod 0.5 mg, weekly IFNβ-1a IM (30 mg) or placebo, in the phase 3, controlled FREEDOMS, FREEDOMS II, and TRANSFORMS fingolimod studies. The ARR was estimated for each treatment group; only relapses that were confirmed by an independent examining neurologist were included in these analyses. Safety assessments included the incidence of adverse events and serious adverse events.Eligible Hispanic patients aged 18-55 years (n = 181) had been treated as follows: fingolimod 0.5 mg (n = 89), IFNβ-1a IM (n = 65), and placebo (n = 27). Hispanic patients treated with fingolimod for up to 2 years had lower ARRs (ARR: 0.22, 95% confidence interval [CI]: 0.14-0.35) than those receiving placebo (ARR: 0.46, 95% CI: 0.24-0.88) or IFNβ-1a IM (ARR: 0.34, 95% CI: 0.18-0.63), with relative reductions of 52% and 35%, respectively. A transient decrease in heart rate that started to attenuate 6 h after fingolimod administration was observed, consistent with the well-characterized pharmacologic effect following fingolimod treatment initiation. No cases of symptomatic bradycardia were reported in Hispanic patients. The incidence of first-degree atrioventricular block was low and similar across all treatment groups (3.1-4.5%). The safety profile of fingolimod in Hispanic patients was consistent with that reported in the overall population of each study.Overall, this study demonstrates that fingolimod is efficacious and well tolerated in Hispanic patients with RRMS.
- 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.