Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 858
Filtrar
1.
Acta Neurol Taiwan ; 29(3): 90-94, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32996117

RESUMEN

PURPOSE: A case report with a review of the current literature concerning cutaneous necrosis has occasionally been reported in interferon therapy. CASE REPORT: We report a 19-year-old woman diagnosed multiple sclerosis for three years. She selfinjected the standard dose of recombinant interferonß-1a (12 million units) subcutaneously three times a week. Severe necrotizing cutaneous reactions over abdomen Happened and she must receive parental antibiotics and surgical debridement. CONCLUSION: Our observation emphasizes the importance of educating patients on the proper selfadministration of subcutaneous injections of interferon ß.


Asunto(s)
Celulitis (Flemón) , Interferón beta-1a/uso terapéutico , Celulitis (Flemón)/tratamiento farmacológico , Femenino , Humanos , Factores Inmunológicos , Interferón beta/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Adulto Joven
2.
Georgian Med News ; (298): 84-88, 2020 Jan.
Artículo en Ruso | MEDLINE | ID: mdl-32141856

RESUMEN

About 30-40% of multiple sclerosis (MS) patients treated with interferon-beta (IFN-ß) develop neutralizing antibodies (NABs) to IFN-ß. NABs reduce bioavailability of IFN-ß, which leads to a decrease in the therapy effectiveness. The introduction of IFN-ß induce production of several proteins, which are used as markers of the therapy effectiveness. In this study, we assessed the prognostic significance of MS activity biomarkers in relation to the clinical data of MS patients treated with IFN-ß. The study involved 30 MS patients receiving IFN-ß. The average duration of therapy was 3.5 (3.4-5.3) years. The study showed the prevalence of NAbs formation in MS patients was 13% of cases, a year later - 30%. The level of viperin in patients without exacerbations during the observation period was lower than in patients with exacerbations. The study revealed the prognostic significance of viperin in relation to the frequency of exacerbations: viperin concentration above 0.2 ng / ml is a risk factor for exacerbation of MS. The results of this study suggest that viperin concentration in the serum could be used a prognostic marker in MS patients treated with interferons.


Asunto(s)
Interferón beta/farmacología , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológico , Anticuerpos/análisis , Anticuerpos/sangre , Anticuerpos Neutralizantes , Biomarcadores/análisis , Biomarcadores/sangre , Georgia (República)/epidemiología , Humanos , Interferón beta/efectos adversos , Interferón beta/uso terapéutico , Esclerosis Múltiple/sangre , Esclerosis Múltiple/epidemiología , Prevalencia , Pronóstico , Resultado del Tratamiento
3.
Curr Med Res Opin ; 36(2): 251-260, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31530036

RESUMEN

Healthcare systems vary greatly between countries. International, evidence-based guidelines for the management of multiple sclerosis (MS) may need to be adapted for use in particular countries. Two years ago, the authors published a comprehensive consensus guideline for the management of MS in Qatar. Since that time, the availability of disease-modifying treatments for relapsing-remitting MS (RRMS), and our understanding of how to apply those treatments, has increased. The authors present an update to our guidance, focussing on the management of relapsing-remitting RRMS. In particular, the authors consider the optimal use of different DMTs in patients presenting with mild, medium or high disease activity.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Consenso , Dimetilfumarato/efectos adversos , Dimetilfumarato/uso terapéutico , Servicios de Planificación Familiar , Acetato de Glatiramer/efectos adversos , Acetato de Glatiramer/uso terapéutico , Humanos , Interferón beta/efectos adversos , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/inmunología , Natalizumab/uso terapéutico , Prioridad del Paciente
4.
PLoS One ; 14(12): e0227120, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31887199

RESUMEN

BACKGROUND: Interferon-beta (IFN-beta) is a commonly used treatment for multiple sclerosis (MS). Current guidelines recommend cessation of treatment during pregnancy, however the results of past studies on the safety of prenatal exposure to IFN-beta have been conflicting. A large scale study of a population of MS women is therefore warranted. OBJECTIVES: To assess whether, among those born to women with MS, infants prenatally exposed to IFN-beta show evidence of smaller size at birth relative to infants which were not prenatally exposed to any MS disease modifying drugs. METHODS: Swedish and Finnish register data was used. Births to women with MS in Sweden and Finland between 2005-2014 for which a birth measurement for weight, height, and head circumference was available were included. The exposure window was from 6 months prior to LMP to the end of pregnancy. RESULTS: In Sweden, 411 pregnancies were identified as exposed to IFN-beta during the exposure window, and 835 pregnancies were counted as unexposed to any MS DMD. The corresponding numbers for Finland were 232 and 331 respectively. Infants prenatally exposed to interferon-beta were on average 28 grams heavier (p = 0.17), 0.01 cm longer (p = 0.95), and had head circumferences 0.14 cm larger (p = 0.13) in Sweden. In Finland, infants were 50 grams lighter (p = 0.27), 0.02 cm shorter (p = 0.92) and had head circumferences 0.22 cm smaller (p = 0.15) relative to those unexposed. CONCLUSIONS: This study provides evidence that exposure to IFN-beta during pregnancy does not influence birth weight, length, or head circumference.


Asunto(s)
Peso al Nacer/efectos de los fármacos , Estatura/efectos de los fármacos , Interferón beta/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Adulto , Femenino , Finlandia , Humanos , Recién Nacido , Intercambio Materno-Fetal , Esclerosis Múltiple/inmunología , Embarazo , Complicaciones del Embarazo/inmunología , Sistema de Registros/estadística & datos numéricos , Suecia
5.
Neuroimage Clin ; 24: 102020, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31734534

RESUMEN

Treatment with interferon (IFN) has been associated with depressive side effects. Previous neuroimaging studies have provided information about changes in brain activation patterns in patients under treatment with IFN-alpha, but the effect of other IFNs, or the role of the underlying disease, has yet to be clarified. In the present fMRI study, we looked at brain changes after 8 days of IFN-beta treatment in N = =17 healthy volunteers, thus avoiding the possible confound of the effects of underlying pathology in studies of IFN-treated patients with neurological or other medical disorders. We followed a symptom dimensional approach by simultaneously investigating two distinct symptom domains of depressiveness: negative affect (amygdala) and appetitive motivation (ventral striatum). In these early phases of IFN treatment we detected a selective change in neural substrates of appetitive motivation, consistent with the predominant symptomatic change recorded in psychopathology ratings. In contrast, the fMRI phenotype of negative affect, which is known to characterize disorders of affect involving anxiety and depressiveness as well as individual vulnerability to depression, was unchanged after treatment. These findings suggest that IFN may induce an affective syndrome through a mechanism involving down-regulation of appetitive motivation.


Asunto(s)
Afecto , Amígdala del Cerebelo , Ansiedad , Depresión , Factores Inmunológicos/farmacología , Interferón beta/farmacología , Motivación , Recompensa , Estriado Ventral , Adolescente , Adulto , Afecto/efectos de los fármacos , Afecto/fisiología , Anciano , Amígdala del Cerebelo/diagnóstico por imagen , Amígdala del Cerebelo/efectos de los fármacos , Amígdala del Cerebelo/fisiología , Ansiedad/inducido químicamente , Ansiedad/diagnóstico por imagen , Ansiedad/fisiopatología , Depresión/inducido químicamente , Depresión/diagnóstico por imagen , Depresión/fisiopatología , Expresión Facial , Reconocimiento Facial/efectos de los fármacos , Reconocimiento Facial/fisiología , Femenino , Humanos , Factores Inmunológicos/efectos adversos , Interferón beta/efectos adversos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Motivación/efectos de los fármacos , Motivación/fisiología , Estriado Ventral/diagnóstico por imagen , Estriado Ventral/efectos de los fármacos , Estriado Ventral/fisiología , Adulto Joven
7.
Pharmacoepidemiol Drug Saf ; 28(4): 556-560, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30834654

RESUMEN

PURPOSE: The purpose of this study is to describe dispensing patterns and comparative safety of disease-modifying therapies (DMTs) during pregnancy in women with multiple sclerosis (MS). METHODS: We identified pregnancies from the Truven Health Marketscan® Commercial Claims and Encounters Database (2011-2015) and ascertained MS before delivery from inpatient and outpatient claims. We computed the proportion of women with DMT dispensing claims around pregnancy and estimated risk ratios of spontaneous abortion, infections, cesarean section, preterm delivery, poor fetal growth, preeclampsia, and major structural malformations by DMT exposure. RESULTS: Of 984 058 pregnancies, 1649 were to women with MS. Thirty-five percent of women with MS filled a prescription for a DMT in the 90 days before pregnancy. DMT use declined during pregnancy but increased again after delivery. Glatiramer acetate and interferon beta were most commonly dispensed. Pregnancies with and without early DMT exposure had similar risks of outcomes to one another and to pregnancies in women without MS. Small numbers did not allow evaluation of specific DMTs. CONCLUSIONS: Approximately one third of commercially insured women with MS in the United States uses DMTs before conception. Neither MS itself nor early pregnancy use of DMTs overall seems to be associated with a substantial risk of adverse pregnancy outcomes.


Asunto(s)
Inmunosupresores/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Complicaciones del Embarazo/tratamiento farmacológico , Anomalías Inducidas por Medicamentos/epidemiología , Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/epidemiología , Reclamos Administrativos en el Cuidado de la Salud/estadística & datos numéricos , Adulto , Cesárea/estadística & datos numéricos , Femenino , Acetato de Glatiramer/administración & dosificación , Acetato de Glatiramer/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Recién Nacido , Interferón beta/administración & dosificación , Interferón beta/efectos adversos , Embarazo , Nacimiento Prematuro/inducido químicamente , Nacimiento Prematuro/epidemiología , Estados Unidos/epidemiología
9.
Mult Scler Relat Disord ; 28: 273-275, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30639829

RESUMEN

Drug-Induced Pulmonary Arterial Hypertension (PAH) represents a well-known entity, predominantly related to anorexigens. Interferon-ß (IFN) is considered to be a drug with a possible risk of inducing PAH. We report a patient with Multiple Sclerosis treated with IFN-ß who diagnosed with PAH and her course of disease under specific PAH drug therapy. A review of the literature in IFN-ß-induced PAH is provided.


Asunto(s)
Hipertensión Pulmonar/etiología , Factores Inmunológicos/efectos adversos , Interferón beta/efectos adversos , Esclerosis Múltiple/terapia , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/tratamiento farmacológico , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico
11.
J Clin Lipidol ; 13(1): 62-69, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30514621

RESUMEN

BACKGROUND: Autoantibodies against glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) cause chylomicronemia by blocking the ability of GPIHBP1 to bind lipoprotein lipase (LPL) and transport the enzyme to its site of action in the capillary lumen. OBJECTIVE: A patient with multiple sclerosis developed chylomicronemia during interferon (IFN) ß1a therapy. The chylomicronemia resolved when the IFN ß1a therapy was discontinued. Here, we sought to determine whether the drug-induced chylomicronemia was caused by GPIHBP1 autoantibodies. METHODS: We tested plasma samples collected during and after IFN ß1a therapy for GPIHBP1 autoantibodies (by western blotting and with enzyme-linked immunosorbent assays). We also tested whether the patient's plasma blocked the binding of LPL to GPIHBP1 on GPIHBP1-expressing cells. RESULTS: During IFN ß1a therapy, the plasma contained GPIHBP1 autoantibodies, and those autoantibodies blocked GPIHBP1's ability to bind LPL. Thus, the chylomicronemia was because of the GPIHBP1 autoantibody syndrome. Consistent with that diagnosis, the plasma levels of GPIHBP1 and LPL were very low. After IFN ß1a therapy was stopped, the plasma triglyceride levels returned to normal, and GPIHBP1 autoantibodies were undetectable. CONCLUSION: The appearance of GPIHBP1 autoantibodies during IFN ß1a therapy caused chylomicronemia. The GPIHBP1 autoantibodies disappeared when the IFN ß1a therapy was stopped, and the plasma triglyceride levels fell within the normal range.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Hiperlipoproteinemia Tipo I/inmunología , Interferón beta/efectos adversos , Esclerosis Múltiple/terapia , Receptores de Lipoproteína/inmunología , Adulto , Autoanticuerpos/sangre , Enfermedades Autoinmunes/etiología , Células Cultivadas , Femenino , Humanos , Hiperlipoproteinemia Tipo I/etiología , Interferón beta/uso terapéutico , Esclerosis Múltiple/complicaciones , Unión Proteica , Síndrome , Triglicéridos/sangre , Privación de Tratamiento
12.
J Am Acad Dermatol ; 80(4): 922-930.e4, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30003983

RESUMEN

BACKGROUND: Without clear evidence, selecting among the existing immunotherapeutic options for warts remains challenging. OBJECTIVE: Through network meta-analyses, we aimed to evaluate the comparative efficacy of different intralesional immunotherapeutic modalities. METHODS: We included randomized controlled trials comparing intralesional immunotherapeutic modalities to cryotherapy, placebo, or imiquimod. All outcomes were presented as odds ratios (ORs) with 95% confidence intervals. Both conventional and network meta-analyses (with a frequentist approach) were conducted on R software. The P-score was used to rank different treatments. RESULTS: Network meta-analysis of 17 randomized controlled trials (1676 patients) showed that PPD (purified protein derivative vaccine, OR 39.56), MMR (measles, mumps, rubella vaccine, OR 17.46) and interferon ß (OR 15.55) had the highest efficacy in terms of complete recovery at the primary site compared with placebo. Regarding complete recovery at the distant site, autoinoculation (OR 79.95), PPD (OR 42.95), and MMR (OR 15.39) were all statistically superior to placebo. According to the P-score, MMR was more effective than other modalities in reducing the recurrence rate at the same site. LIMITATIONS: Relatively small sample size in some comparisons and variability in baseline characteristics. CONCLUSION: PPD and MMR were the most effective in achieving complete primary and distant recovery (along with autoinoculation for distant recovery) and reducing the recurrence rate at the same site compared with cryotherapy and other immunotherapeutic modalities.


Asunto(s)
Inmunoterapia , Verrugas/terapia , Antivirales/efectos adversos , Antivirales/uso terapéutico , Crioterapia/efectos adversos , Humanos , Imiquimod/efectos adversos , Imiquimod/uso terapéutico , Inmunoterapia/efectos adversos , Inmunoterapia/métodos , Inyecciones Intralesiones , Interferón beta/efectos adversos , Interferón beta/uso terapéutico , Metaanálisis en Red , Vacunas/efectos adversos , Vacunas/uso terapéutico
13.
Cochrane Database Syst Rev ; 12: CD011644, 2018 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-30521693

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six months following infection with the virus. Another commonly used definition of acute HCV infection is the absence of HCV antibody and subsequent seroconversion (presence of HCV antibody in a person who was previously negative for HCV antibody). Approximately 40% to 95% of people with acute HCV infection develop chronic HCV infection, that is, have persistent HCV RNA in their blood. In 2010, an estimated 160 million people worldwide (2% to 3% of the world's population) had chronic HCV infection. The optimal pharmacological treatment of acute HCV remains controversial. Chronic HCV infection can damage the liver. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in the treatment of acute HCV infection through a network meta-analysis and to generate rankings of the available pharmacological treatments according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead we assessed the comparative benefits and harms of different interventions versus each other or versus no intervention using standard Cochrane methodology. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and randomised controlled trials registers to April 2016 to identify randomised clinical trials on pharmacological interventions for acute HCV infection. SELECTION CRITERIA: We included only randomised clinical trials (irrespective of language, blinding, or publication status) in participants with acute HCV infection. We excluded trials which included previously liver transplanted participants and those with other coexisting viral diseases. We considered any of the various pharmacological interventions compared with placebo or each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We calculated the odds ratio (OR) and rate ratio with 95% confidence intervals (CI) using both fixed-effect and random-effects models based on the available-participant analysis with Review Manager 5. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 10 randomised clinical trials with 488 randomised participants that met our inclusion criteria. All the trials were at high risk of bias in one or more domains. Overall, the evidence for all the outcomes was very low quality evidence. Nine trials (467 participants) provided information for one or more outcomes. Three trials (99 participants) compared interferon-alpha versus no intervention. Three trials (90 participants) compared interferon-beta versus no intervention. One trial (21 participants) compared pegylated interferon-alpha versus no intervention, but it did not provide any data for analysis. One trial (41 participants) compared MTH-68/B vaccine versus no intervention. Two trials (237 participants) compared pegylated interferon-alpha versus pegylated interferon-alpha plus ribavirin. None of the trials compared direct-acting antivirals versus placebo or other interventions. The mean or median follow-up period in the trials ranged from six to 36 months.There was no short-term mortality (less than one year) in any group in any trial except for one trial where one participant died in the pegylated interferon-alpha plus ribavirin group (1/95: 1.1%). In the trials that reported follow-up beyond one year, there were no further deaths. The number of serious adverse events was higher with pegylated interferon-alpha plus ribavirin than with pegylated interferon-alpha (rate ratio 2.74, 95% CI 1.40 to 5.33; participants = 237; trials = 2; I2 = 0%). The proportion of people with any adverse events was higher with interferon-alpha and interferon-beta compared with no intervention (OR 203.00, 95% CI 9.01 to 4574.81; participants = 33; trials = 1 and OR 27.88, 95% CI 1.48 to 526.12; participants = 40; trials = 1). None of the trials reported health-related quality of life, liver transplantation, decompensated liver disease, cirrhosis, or hepatocellular carcinoma. The proportion of people with chronic HCV infection as indicated by the lack of sustained virological response was lower in the interferon-alpha group versus no intervention (OR 0.27, 95% CI 0.09 to 0.76; participants = 99; trials = 3; I2 = 0%). The differences between the groups were imprecise or not estimable (because neither group had any events) for all the remaining comparisons.Four of the 10 trials (40%) received financial or other assistance from pharmaceutical companies who would benefit from the findings of the research; the source of funding was not available in five trials (50%), and one trial (10%) was funded by a hospital. AUTHORS' CONCLUSIONS: Very low quality evidence suggests that interferon-alpha may decrease the incidence of chronic HCV infection as measured by sustained virological response. However, the clinical impact such as improvement in health-related quality of life, reduction in cirrhosis, decompensated liver disease, and liver transplantation has not been reported. It is also not clear whether this finding is applicable in the current clinical setting dominated by the use of pegylated interferons and direct-acting antivirals, although we found no evidence to support that pegylated interferons or ribavirin or both are effective in people with acute HCV infection. We could find no randomised trials comparing direct-acting antivirals with placebo or other interventions for acute HCV infection. There is significant uncertainty in the benefits and harms of the interventions, and high-quality randomised clinical trials are required.


Asunto(s)
Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Interferón beta/uso terapéutico , Ribavirina/uso terapéutico , Vacunas contra Hepatitis Viral/uso terapéutico , Enfermedad Aguda , Antivirales/efectos adversos , Hepatitis C/mortalidad , Humanos , Interferón-alfa/efectos adversos , Interferón beta/efectos adversos , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Ribavirina/efectos adversos
15.
N Engl J Med ; 379(11): 1017-1027, 2018 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-30207920

RESUMEN

BACKGROUND: Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population. METHODS: In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 µg per week for up to 2 years. The primary end point was the annualized relapse rate. RESULTS: Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient). CONCLUSIONS: Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).


Asunto(s)
Clorhidrato de Fingolimod/uso terapéutico , Factores Inmunológicos/uso terapéutico , Interferón beta/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Administración Oral , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Niño , Femenino , Clorhidrato de Fingolimod/efectos adversos , Cefalea/inducido químicamente , Humanos , Factores Inmunológicos/efectos adversos , Infecciones/inducido químicamente , Inyecciones Intramusculares , Interferón beta/efectos adversos , Leucopenia/inducido químicamente , Imagen por Resonancia Magnética , Masculino , Prevención Secundaria
16.
Mult Scler Relat Disord ; 26: 192-200, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30268040

RESUMEN

OBJECTIVES: To compare the liver safety profile of interferon ß (IFN ß) and teriflunomide in patients with multiple sclerosis. METHODS: A network meta-analysis was carried out following the Cochrane Collaboration methodology. All trials comparing all types of IFN ß with teriflunomide, or disease-modifying drugs, or placebo in RRMS were included. An indirect comparison network meta-analysis within a Bayesian framework with STATA (version 13.0) was done for this study. RESULTS: The database searches yielded 284 titles, with 15 records as duplicates. One study was identified by manually searching. Thirteen articles were included in the systematic review. Twelve studies compared IFN ß (4203 patients) vs another DMT. Four studies evaluated the effectiveness and safety of teriflunomide (906 patients) vs another DMT. Six studies reported drug-induced liver injury as per the Hy's Law. However, only one study had a direct comparison and reported no cases of liver toxicity in either group, so it was not possible to estimate the OR. The indirect comparisons metanalysis shows that there was no statistically-significant difference between teriflunomide and IFN ß (OR 1.09, 95% CI 0.02-2.16). CONCLUSIONS: There were no significant difference when comparing IFN ß and teriflunomide in terms of liver failure or elevation of transaminases.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Crotonatos/efectos adversos , Factores Inmunológicos/efectos adversos , Interferón beta/efectos adversos , Hígado/efectos de los fármacos , Esclerosis Múltiple/tratamiento farmacológico , Toluidinas/efectos adversos , Humanos
17.
JCI Insight ; 3(11)2018 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-29875313

RESUMEN

Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-ß is an established treatment for MS; however, up to 30% of IFN-ß-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-ß. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-ß administration. Reduced monocyte NOTCH2 expression in nADA+ MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA+ patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-ß administration.


Asunto(s)
Hipersensibilidad a las Drogas/diagnóstico , Interferón beta/efectos adversos , Monocitos/metabolismo , Esclerosis Múltiple/tratamiento farmacológico , Receptor Notch2/metabolismo , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Biomarcadores/análisis , Biomarcadores/metabolismo , Estudios Transversales , Hipersensibilidad a las Drogas/sangre , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Interferón beta/inmunología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Receptor Notch2/análisis
19.
J Neurol Neurosurg Psychiatry ; 89(10): 1050-1056, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-29602795

RESUMEN

OBJECTIVE: Little is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters. METHODS: Using population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996-2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count. Results were reported as adjusted HRs (aHRs). RESULTS: Of 6793 MS cases, followed for 8.5 years (mean), 1716 (25.3%) were DMT exposed. Relative to no DMT, exposure to any first-generation DMT (beta-interferon or glatiramer acetate) was not associated with infection-related physician claims (aHR: 0.96; 95% CI 0.89 to 1.02), nor was exposure to these drug classes when assessed separately. Exposure to any second-generation DMT (oral DMT or natalizumab) was associated with an increased hazard of an infection-related physician claim (aHR: 1.47; 95% CI 1.16 to 1.85); when assessed individually, the association was significant for natalizumab (aHR: 1.59; 95% CI 1.19 to 2.11) but not the oral DMTs (aHR: 1.17; 95% CI 0.88 to 1.56). While no DMTs were associated with infection-related hospital claims, these hospitalisations were also uncommon. CONCLUSION: Exposure to first-generation DMTs was not associated with an altered infection risk. However, exposure to the second-generation DMTs was, with natalizumab associated with a 59% increased risk of an infection-related physician claim. Continued pharmacovigilance is warranted, including an investigation of the DMT-associated infection burden on patient outcomes.


Asunto(s)
Acetato de Glatiramer/efectos adversos , Inmunosupresores/efectos adversos , Infecciones/epidemiología , Infecciones/etiología , Interferón beta/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/efectos adversos , Adulto , Colombia Británica/epidemiología , Bases de Datos Factuales , Femenino , Acetato de Glatiramer/uso terapéutico , Humanos , Incidencia , Interferón beta/uso terapéutico , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/epidemiología , Natalizumab/uso terapéutico , Estudios Retrospectivos , Riesgo
20.
Expert Opin Biol Ther ; 18(6): 665-680, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29624084

RESUMEN

INTRODUCTION: Multiple sclerosis (MS) is a chronic and disabling immune-mediated disease of the central nervous system. Beta-interferons are the first approved and still the most widely used first-line disease-modifying treatment in MS. AREAS COVERED: Here we focus on recent developments in pharmacology and delivery systems of beta-interferons, and discuss their place within current state of the art therapeutic approaches. We briefly review the clinical trials for classical and PEGylated formulations, emphasizing effectiveness, safety concerns, and tolerability. The mechanisms of action of IFN-ß in view of MS pathogenesis are also debated EXPERT OPINION: Though only modestly efficient in reducing the annualized relapse rate, beta-interferons remain a valid first-line option due to their good long-term safety profile and cost-efficacy. Moreover, they are endogenous class II cytokines essential for mounting an effective antiviral response, and they may interact with putative MS triggering factors such as Epstein-Barr virus infection and human endogenous retroviruses. Recent improvements in formulations, delivery devices and drug regimens tackle the tolerability and adherence issues frequently seen with these drugs, and scientific advances may offer means for a better selection of patients. Although a well-established immunomodulatory treatment, beta-interferons have not said their last word in the management of MS.


Asunto(s)
Interferón beta/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Humanos , Inmunoterapia/métodos , Interferón beta/efectos adversos , Esclerosis Múltiple/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...