Respuesta al tratamiento con Interferón beta-1a en pacientes con esclerosis múltiple remitente-recurrente / Response to treatment with Interferon beta-1a in patients with relapsing-remitting multiple sclerosis

RESUMEN Fundamento: los fármacos modificadores, en la esclerosis múltiple, tienen la finalidad de reducir la frecuencia de recaídas, retardar la progresión de la discapacidad, así como la aparición de nuevas lesiones en el Sistema Nervioso Central. Objetivo determinar los indicadores precoces de respuesta al tratamiento con IFNb-1ª en pacientes con esclerosis múltiple remitente-recurrente. Métodos: estudio observacional, analítico de cohorte con prospectiva longitudinal en los pacientes con diagnóstico de esclerosis múltiple. Se conformaron dos cohortes de estudio, cada una con 39 pacientes. Resultados: la media y desviación estándar de la escala ampliada del estado de discapacidad a los 36 meses fue de 2.37 ± 1.86 en el grupo estudio y en el control de 3.15 ± 2.1. En los brotes de .13 ± .33 en el grupo estudio y en el grupo control de .41 ± .59. Las lesiones nuevas en T2 tras los 12 primeros meses de tratamiento fue de 0.90 ± 1.16 para el grupo estudio y para el control de 1 ± 1.10. La progresión por escala ampliada del estado de discapacidad, la tasa anualizada de brotes antes del tratamiento, la edad de inicio de la enfermedad, tiempo de evolución de la enfermedad y lesiones que realzan gadolinio se asociaron de forma significativa con la razón de ventaja de mayor probabilidad de no progresión para el grupo estudio con respecto al grupo control por la variable combinada progresión por escala ampliada del estado de discapacidad y brotes. Conclusiones: se identificaron indicadores precoces de respuesta al tratamiento con el interferón beta-1a, que ayudan a valorar la respuesta al tratamiento de forma precoz, lo que repercute de forma positiva en la evolución de la enfermedad.

ABSTRACT Background: multiple sclerosis modifying drugs are intended to reduce the frequency of relapses, delay the progression of disability, as well as the appearance of new lesions in the Central Nervous System. Objective: to determine the early indicators of response to treatment with IFNb-1a. Methods: Observational, analytical longitudinal prospective cohort study in patients diagnosed with multiple sclerosis. Two study cohorts were formed, each with 39 patients. Results the mean and standard deviation of the expanded disability status scale at 36 months was 2.37 ± 1.86 in the study group and 3.15 ± 2.1 in the control group. In the outbreaks of .13 ± .33 in the study group and in the control group of .41 ± .59. New lesions in T2 after the first 12 months of treatment was 0.90 ± 1.16 for the study group and 1 ± 1.10 for the control. Extended-scale progression of disability status, pretreatment annualized relapse rate, age of disease onset, time since disease progression, and gadolinium-enhancing lesions were significantly associated with the odds ratio of older Probability of non-progression for the study group with respect to the control group for the combined variable progression by extended disability status scale and relapses. Conclusions: early indicators of response to treatment with interferon beta-1a were identified; that help assess the response to treatment early, which has a positive impact on the evolution of the disease.

Evolución clínica de pacientes con esclerosis múltiple remitente- recurrente tratados con interferón beta-1a / Clinical evolution of patients with relapsing-remitting multiple sclerosis treated with interferon beta-1a

RESUMEN Introducción: El inicio de la terapia con interferón ha sido y es el primer paso en el tratamiento de muchos pacientes con esclerosis múltiple, con el propósito de retrasar la progresión de la enfermedad. Objetivo: Identificar los marcadores clínicos de respuesta al tratamiento con interferón beta-1a de pacientes con esclerosis múltiple remitente-recurrente. Métodos: Se realizó un estudio observacional, descriptivo, longitudinal, prospectivo, de una serie de casos de pacientes con diagnóstico de esclerosis múltiple remitente-recurrente, que recibían tratamiento con interferón beta-1a, en el periodo comprendido entre enero del 2014 a diciembre del 2020. Se incluyeron los 39 pacientes. Resultados: La media de edad fue de 34,54 años. La media del nivel de discapacidad en la línea base, 12, 24 y a los 36 meses fue de 1,76; 1,91; 2,1 y 2,37 respectivamente. La media de los brotes en la línea base, 12, 24 y a los 36 meses fue de 1,13; 0,26; 0,38 y 0,13 respectivamente. Se muestra la cifra de progresiones inferior en un 51 % a los 36 meses. La razón de ventajas (odds ratio) para la no presencia de brotes se muestra entre 2 y 4 veces en estos pacientes. Conclusiones: Se identifican marcadores clínicos de respuesta al tratamiento con interferón beta-1a que ayudan a valorar la respuesta al tratamiento, lo cual repercute de forma positiva en la evolución de la enfermedad.

ABSTRACT Introduction: The initiation of interferon therapy has been and is the first step in the treatment of many patients with multiple sclerosis, with the aim of delaying the progression of the disease. Objective: To identify the clinical markers of response to treatment with Interferon beta-1a in patients with relapsing-remitting multiple sclerosis. Methods: An observational, descriptive, longitudinal, prospective study was carried out of a series of cases of patients diagnosed with relapsing-remitting multiple sclerosis, who received treatment with interferon beta-1a, in the period between January 2014 and December 2020. All 39 patients were included. Results: The mean age was 34.54 years. The mean disability level at baseline, 12, 24, and 36 months was 1.76; 1.91; 2.1 and 2.37 respectively. The mean number of flares at baseline, 12, 24, and 36 months was 1.13; 0.26; 0.38 and 0.13 respectively. The number of progressions lower by 51% at 36 months is shown. The odds ratio for the absence of relapses is between 2 and 4 times in these patients. Conclusions: Clinical markers of response to treatment with Interferon beta-1a are identified that help assess the response to treatment, which has a positive impact on the evolution of the disease.

Esclerosis múltiple: reacciones adversas a medicamentos en pacientes bajo ley 20850, Hospital Regional de Talca / Multiple sclerosis: adverse drug reactions in patients under law 20850, Hospital Regional de Talca

INTRODUCTION: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system, which occurs in up to 85% of cases as relapsing remitting (RR), with episodes of neurological dysfunction partially forwarded. Its treatment in Chile is financially protected by the Explicit Health Guarantees (GES) and Law 20,850 on high-cost diseases. The Regional Hospital of Talca (HRT) has 25 patients benefiting from Law 20,850 in treatment with second-line biologic therapy. Adverse reactions (RAM) to the use of these drugs have been described and to date there are no case reports or studies of significant adverse events in Chile. Objectives: To present the experience of the use of biologic therapy in EMRR in HRT, in relation to adverse events. METHODS: A review of the current guidelines in Chile for the treatment of relapsing-remitting multiple sclerosis and the protocol of law 20,850 was carried out, the clinical records of 25 patients benefiting from the law in the HRT were reviewed, with emphasis on the adverse events presented before First and second line therapies and the con sequences of these events on the continuity of therapy. RESULTS: Half of the patients who started their treatment with first-line drugs had adverse effects, of which 28% involved a change in therapy, the remaining changed from therapy due to failure to treatment. Of the 26 patients included in the sample, 24 are currently using second-line drugs. The profile of adverse effects should be a variable to consider when indicating a therapy for MS.

Effects of recombinant human interferon β1a on the chondrogenic differentiation of human bone marrow mesenchymal stem cell / 生物工程学报

Recombinant human interferon beta (rhIFN-β) is a glycoprotein produced by genetically engineered cells and has anti-virus, anti-tumor and immunoregulation functions. Although studies have shown that other subtypes of IFN such as IFN-γ affects cell proliferation and differentiation to some extent, the effect of rhIFN-β on chondrogenic differentiation of human bone marrow mesenchymal stem cells (hMSCs) is less known. In this study we studied the effect of rhIFN-β on the chondrogenic differentiation of hMSCs by inducing hMSCs into cartilage pellet via adding IFN-β1a into regular TGF-β3 chondrogenic differentiation medium. We collected the induced pellets and then detected GAG content, assessed pellets size, observed agreecan using alcian blue staining, and analyzed the expression of Sox and CollangenⅡusing real-time PCR and Western blotting. Addition of 100 ng/mL IFN-β1a to regular TGF-β3 chondrogenic differentiation medium could improve the concentration of GAG, increase the size of pellets, promote the formation of aggrecan and up-regulate the expression of CollangenII and Sox9. IFN-β1a combined with TGF-β3 could promote chondrogenic differentiation of hMSCs.

Effects of Systemic and Local Interferon Beta-1a on Epidural Fibrosis

STUDY DESIGN: Level 1 randomized controlled study. PURPOSE: To investigate the effects of systemic and local interferon-beta-1a (IFN-β-1a) on prevention of epidural fibrosis using histopathological parameters. OVERVIEW OF LITERATURE: Epidural fibrosis involves fibroblastic invasion of nerve roots into the epidural space. Formation of dense fibrous tissue causes lumbar and radicular pain. Many surgical techniques and several materials have been proposed in the literature, but no study has assessed the effect of IFN-β-1a on prevention of epidural fibrosis. METHODS: Forty-eight adult female Sprague-Dawley rats were divided into six groups of eight: sham group, control group, systemic 44 μg IFN-β-1a group and 22 μg IFN-β-1a group (after laminectomy and discectomy, 0.28 mL and 0.14 mL IFN-β-1a applied subcutaneously three times for a week, respectively), local 44 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.28 mL IFN-β-1a on the surgical area), and local 22 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.14 mL IFN-β-1a on the surgical area). All rats were sacrificed after 4 weeks and groups were evaluated histopathologically. RESULTS: Compared with sham and control groups, significantly less epidural fibrosis, dural adhesion, and fibroblast cell density were observed in the local and systemic 44 μg IFN-β-1a groups. No other differences were evident between the local and systemic groups. CONCLUSIONS: IFN-β-1a is effective in preventing epidural fibrosis with systemic and local application.

Effects of Systemic and Local Interferon Beta-1a on Epidural Fibrosis

STUDY DESIGN: Level 1 randomized controlled study. PURPOSE: To investigate the effects of systemic and local interferon-beta-1a (IFN-β-1a) on prevention of epidural fibrosis using histopathological parameters. OVERVIEW OF LITERATURE: Epidural fibrosis involves fibroblastic invasion of nerve roots into the epidural space. Formation of dense fibrous tissue causes lumbar and radicular pain. Many surgical techniques and several materials have been proposed in the literature, but no study has assessed the effect of IFN-β-1a on prevention of epidural fibrosis. METHODS: Forty-eight adult female Sprague-Dawley rats were divided into six groups of eight: sham group, control group, systemic 44 μg IFN-β-1a group and 22 μg IFN-β-1a group (after laminectomy and discectomy, 0.28 mL and 0.14 mL IFN-β-1a applied subcutaneously three times for a week, respectively), local 44 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.28 mL IFN-β-1a on the surgical area), and local 22 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.14 mL IFN-β-1a on the surgical area). All rats were sacrificed after 4 weeks and groups were evaluated histopathologically. RESULTS: Compared with sham and control groups, significantly less epidural fibrosis, dural adhesion, and fibroblast cell density were observed in the local and systemic 44 μg IFN-β-1a groups. No other differences were evident between the local and systemic groups. CONCLUSIONS: IFN-β-1a is effective in preventing epidural fibrosis with systemic and local application.

Interferon beta11a treatment in htlv-1-associatd myelopathy/tropical spastic pparaparesis: a case report / Tratamento com interferon beta-1a em mielopatia associada ao HTLV-1/paraparesia espástica tropical: relato de caso

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.

Descreve-se caso de mielopatia associada ao HTLV-1/paraparesia espástica tropical tratada com interferon beta-1a em paciente jovem de 21 anos e com história de dermatite infecciosa na infância. Foi estabelecida clinicamente paraparesia espástica tropical (HAM/TSP), confirmada laboratorialmente pela presença de anticorpos para HTLV-1 no LCR e excluídas caxumba, citomegalovirus, Epstein-Barr, esquistossomose, herpes virus 1 e 2, rubéola, sarampo, toxoplasmose varicela-zoster, hepatite, HIV e sífilis por sorologias. Foi diagnosticada bexiga neurogênica, com quadro clínico de nictúria, urgência urinária, parestesia no membro inferior esquerdo e discreta redução de força muscular nos membros superiores, mais acentuada nos membros inferiores. Na 4a semana de tratamento com interferon beta-1a houve desaparecimento da urgência urinária e da parestesia e melhora da clínica motora.