Dyspnoea in patients with chronic hepatitis C treated with pegylated interferon and ribavirin.

BACKGROUND: Adverse events attributed to the treatment of chronic hepatitis C patients with pegylated interferon (PEG-IFN) and ribavirin have been widely discussed. Lung disorders have been described, but the respiratory function of these patients during treatment has not been well studied. The aim of this study was to investigate the incidence of dyspnoea and possible changes in lung function associated with the use of PEG-IFN and ribavirin. METHODS: We evaluated clinical data and spirometry in 31 patients with chronic hepatitis C infections prior to treatment, in the 2(nd) week of treatment and in the 12(th) week of treatment. RESULTS: During the follow-up period, 19 patients (61.3%) had dyspnoea. Decreased haemoglobin levels were observed during the study, but there was no significant association with dyspnoea. However, patients with a body mass index (BMI) greater than 25 had a higher incidence of dyspnoea. No significant difference was detected between the values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), or forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) ratio measured during the investigation. However, a significant decrease in FEV1 and FEV1/FVC ratio was observed in patients with later stages of liver fibrosis. CONCLUSIONS: Dyspnoea is a frequently occurring respiratory symptom during chronic hepatitis C treatment, and it is not associated with changes in spirometric parameters in the first 12 weeks of treatment. However, changes in FEV1 and FEV1/FVC can be observed in patients with advanced liver disease in the first 12 weeks of treatment with PEG-IFN and ribavirin.

The Brazilian database on pregnancy in multiple sclerosis.

OBJECTIVES: To report the results from the Brazilian database on multiple sclerosis (MS) and pregnancy. METHODS: Retrospective data from MS patients who became pregnant at any time of their disease were sent to a Brazilian database, using a specific file for this purpose. RESULTS: Data on 128 women (142 pregnancies) from 30 neurologists working in 21 cities in Brazil were collected. Patients' average age at pregnancy was 29.8 years (range 16-42). EDSS at start of pregnancy was 1.5±1.4; and the relapse rate in the year preceding pregnancy was 1.2±1.5. Exposure to medication at any time during pregnancy was high (69.7%): 48.6% to interferon beta; 14.1% to glatiramer acetate; and 7% to other immunomodulatory and immunosuppressive drugs. There was a significant decrease in relapse rate during pregnancy. The prevalence of complications was relatively low, with 4.9% of obstetric and 1.4% neonatal unfavorable outcomes. CONCLUSIONS: Our patients had low degrees of disability, short histories of disease, high drug exposure, and relatively high relapse rate in the year previous to pregnancy. Obstetric and neonatal outcomes were successful in over 90% of our patients.

Severe depression, suicide attempts, and ideation during the use of interferon beta by patients with multiple sclerosis.

BACKGROUND: Interferon (IFN) beta is a safe and efficient drug for treating multiple sclerosis (MS). It is widely accepted that previously depressed patients may get worse when using IFN-beta. There are few reports on the association of IFN-beta and severe depression among patients without previous psychiatric history. METHODS: Discussion of a case of a patient with MS who developed severe depression and attempted suicide while using IFN-beta encouraged us to review the subject. A group of neurologists in Brazil retrospectively gathered together their similar cases for the present paper. RESULTS: The present paper reports on 11 cases of severe depression with suicide attempts or ideation among patients with MS who were using IFN-beta. These patients had no previous history of any psychiatric disease. Nine patients developed the symptoms over a relatively short period (4 months, on average). Two patients developed severe depression after more than 1 year of treatment with IFN-beta. Phobic, aggressive, behavioral, psychotic, and manic symptoms also were observed in these patients, thus suggesting the existence of a complex mood-behavior disorder associated with this drug. Interferon beta withdrawal led to complete remission of symptoms. The Naranjo algorithm established a highly probable association between IFN-beta and this adverse reaction in these patients. CONCLUSIONS: Although uncommon, severe depression with suicide ideation or attempts may be observed during treatment of MS with IFN-beta. This association should not discourage the use of this drug, but physicians need to be aware of this possible adverse event from IFN-beta.

Bioequivalence of two subcutaneous pharmaceutical products of interferon beta la.

Blastoferon, in the following referred to as the test product, is a pharmaceutical product of interferon beta la (CAS 220581-49-7) currently marketed as a biosimilar to the innovator Interferon beta la product (referred to as the reference product). Pharmacokinetics and pharmacodynamIcs assays are critically relevant to demonstrate similarity between biopharmaceuticals. The aims of the present study were to investigate the bioavailability (BA) of the test product (either absolute or relative to the innovator product) and to compare the extent of increase of neopterin concentration following administration of either product. Two studies were performed: initially, an absolute BA assay with i.v. and s.c. injection of test product to 12 healthy subjects. Second, a formal relative BA study with s.c. injections of 88 microg of both products to 24 healthy volunteers. Blood samples for pharmacokinetic and pharmacodynamic profiling were drawn at different intervals after injection. Interferon beta (IFNB) concentrations were determined by ELISA. In the absolute BA study, a single s.c. dose of 44 microg of the test product resulted in a median bioavailable fraction of 29%, a median T(max) of 4 h (4-6) and a C(max) of 3.69 (3.27-4.41) IU x ml(-1). In the relative BA study, values for the test product were: median T(max) of 3 h (2-18), C(max) of 5.39 (4.99-6.31) IU x ml(-1), AUC (0-72) of 142.86 (134.16-190.15) IU x h x ml(-1) and AUC(0-infinity) of 190.95 (174.23-303.13) IU x h x ml(-1). The corresponding values for the innovator product were: T(max) of 3 h (1-24), C(max) of 4.44 (4.12-5.40) IU x ml(-1), AUC(0-72) of 128.77 (121.18-170.92) IU x h x ml(-1) and AUC(0-affinity) of 192.61 (183.04-286.46) IU x h x ml(-1). The AUC(0-72) ratio was 111% (CI 90%: 106-116), the AUC(0-affinity) was 99% (CI 90%: 92-107) and the C(max) ratio was 121% (CI 90%: 112-131). IFNB1a increased neopterin levels in both studies. Both products induced side-effects commonly reported for IFN with no serious adverse events. This study presents pharmacokinetics parameters of the test product and demonstrates similar bioavailability of IFNB1a for both pharmaceutical products.

Increased expression of 2'5'oligoadenylate synthetase and double-stranded RNA dependent protein kinase messenger RNAs on affected skin of systemic sclerosis patients.

Scleroderma or systemic sclerosis (SSc) is an autoimmune disorder of unknown aetiology characterized by excessive collagen synthesis and subsequent deposition on the skin and various internal organs. Interferons (IFNs) are well-known immunomodulators and inhibitors of collagen production. However, IFN therapy has been implicated in the development or exacerbation of several autoimmune diseases, including SSc. We analyzed the expression of several interferon-stimulated genes (ISGs) in affected skin of SSc patients (skin tissue and cultured skin fibroblasts). A set of ISGs (PKR, 2'5'OAS, MxA, and 6-16) was analyzed by real-time PCR using RNA extracted from cultured skin fibroblasts and skin tissue of normal individuals and SSc patients. Both normal and SSc affected skin cultured fibroblasts were sensitive to the IFN treatment and presented similar levels of all ISGs tested. However, PKR and 2'5'OAS mRNA expression levels were significantly higher in the affected skin tissue of SSc patients when compared to normal controls. These data suggest that the IFN system plays a role in the pathogenesis of SSc.

Neuropatía epidémica forma óptica. Ensayo terapeútico con vitaminas e interferones (alfa 2b recombinante y alfa natural) / Optic neuritis epidemic. Therapeutic trial with vitamins and interferons (recombinant alpa-2b and natural alpha)

Con el propósito de evaluar la eficacia, tolerancia y relación riesgo-beneficio de las vitaminas e interferones, se ejecutó un ensayo terpeutico multicéntrico, controlado y sin enmascaramiento, en 108 pacientes ingresados en 4 hospitales de Ciudad de La Habana con el diagnóstico de neuropatía epidémica forma óptica (NOE), durante el primer trimestre de 1992. Los pacientes se distribuyeron en 3 grupos con los siguientes tratamientos : interferón (INF) alfaleucocitario, interferón alfa 2b recombinante, que se asociaron a un esquema de vitaminas A,E, complejo B y ácido fólico, y se diseño un grupo control al que se le administró sólo este esquema. Los pacientes fueron hospitalizados y evaluados al ingreso, al alta hospitalaria (21 días de tratamiento), al mes y a los 3 meses del alta. La eficacia fue determinada siguiendo criterios de mejoría y recuperación, según una valoración oftalmológica integral de los pacientes y se ccalculó la ganancia de la agudeza visual. La tolerancia se estimó monitoreando la aparción de alguna reacción adversa medicamentosa (RAM) durante 21 días

Alteraçöes miocárdicas em AIDS / Changes myocardial in AIDS

A síndorme de imunodeficiência adquirida (AIDS) avança progressivamente, tornando-se uma epidemia de conseqüências imprevisíveis, até o momento. Apesar disso, o conhecimento da doença e as possibilidades terapêuticas no controle das infecçöes oportunistas e também da doença de base, têm possibilitado maior sobrevida aos portadores de AIDS, propiciando que as complicaçöes cardíacas sejam cada vez mais reconhecidas nos aidéticos, já que anteriormente os pacientes sucumbiam precocemente por intercorrências infecciosas. Esta atualizaçäo se propöe a mostrar o estágio de conhecimento do envolvimento do miocárdio na AIDS, manifestado como miocardites e miocardiopatia dilatada, provocada por vários agentes infecciosos e também por açäo tóxica de drogas utilizadas para tratamento das infecçöes oportunistas ou mesmo para o controle do próprio vírus do HIV

Evaluación del interferon alfaleucocitario en el mantenimiento de la respuesta en linfomas no hodgkin / Assessment of alpha-leukocytic interferon in the maintenance of response of non hodgkin lymphoma

Se informan los resultados preliminares de un ensayo piloto donde se trataron 26 pacientes que presentaban un linfoma no hodgkiniano de bajo y moderado grado de malignidad que recibieron quimioterapia con esquema CHOP (8 a 10 c) combinada con radiaciones sobre campos selectivos en enfermedad voluminosa inicial o sitios extraganglionares y una vez determinada la remisión completa, tratamiento con interferon alfaleucocitario a dosis de 6 millones de unidades I.M. 3 veces por semanas hasta cumplir 1 año de tratamiento hasta progresión de enfermedad o toxicidad limitante. Se analiza el intervalo libre de enfermedad: a 30 meses 85 %contra 53 %del control histórico. La sobrevida a 3 años 96,2 %del control histórico

Treatment of recurrent common warts with one low dose of intralesional natural human leukocyte interferon alpha.

Nine patients with recurrent and long lasting common warts were treated with intralesional Hu-IFN-alpha. The schedule was a single dose per wart, ranged between 10(5) and 2 x 10(5) IU. Placebo was also administered in 3 of these patients. Complete remission was observed in 7 of the 9 patients. The pattern of warts involution and the possible interferon mechanism of action are discussed. A significant pain relief, produced by interferon injection was observed in the patients with plantar warts and in one patient with subungueal wart.

Alfa-interferon recombinante no tratamento das hepatites crônicas B e näo-A: resultados preliminares / Recombinant alpha - interferon in the treatment of B and non-A, non-B chronic hepatitis: preliminary results

O interferon-alfa recombinatne (IFN-R) foi administrado a 17 pacientes com hepatite crônica näo-A, näo-B (HCNANB) e com 11 hepatite crônica B (HCB). Apesar da febre sistemática após as primeiras injeçöes (38 a 39 graus Celsius), de outros sintomas como calafrios, dores musculares e cefaléias e das alteraçöes de leucócitos, neutrófilos e por vezes de plaquetas, a tolerância foi considerada satisfatória, sendo os efeitos colaterais reversíveis com o término do tratamento. A eficácia na HCNANB, representada pela normalizaçäo das aminotransferases ou sua reduçäo para níveis inferiores a duas vezes o limite máximo normal, foi observada em quatro de oito pacientes que completaram o tratamento em períodos de três a nove meses. Dos quatro respondedores, um paciente, tratado durante cinco meses, voltou a apresentar elevaçöes das transaminases três meses após o término do tratamento. Por outro lado, em um paciente com HC ativa em fase cirrótica e tratado durante 12 meses observou-se normalizaçäo persistente das aminotransferases, tendo a biópsia de controle revelado acentuada reduçäo do processo inflamatório. A eficácia na HCB, representada pelo desaparecimento do AgHBe e da DNA-polimerase foi observada em três dos sete pacientes que completaram o tratamento. Esses resultados preliminares mostram que o IFN é uma droga promissora, mas sosmente os estudos controlados multicêntricos poderäo estabelecer definitivamente seu valor no tratamento das hepatites crônicas virais

[Recombinant alfa interferon in the treatment of chronic B and non-A, non-B hepatitis: preliminary results]. / Alfa-interferon recombinante no tratamento das hepatities crônicas B e não-A, não-B: resultados preliminares.

Recombinant alpha-interferon (IFN-R) was given to 17 patients with non-A, non-B chronic hepatitis (NANB-CH) and to 11 patients with B chronic hepatitis (B-CH). Fever (100.4 to 102.2 Fahrenheit) was observed in every patient during the early phase of treatment. Other side-effects included rigors, myalgia, headache and laboratory changes such as leucopenia, neutropenia and, in some cases, thrombocytopenia. However, the tolerance was considered acceptable and treatment had to be interrupted in only one patient presenting generalized mucosal lesions attributed to a hypersensitivity reaction. The response to IFN-R in NANB-CH was considered positive when serum aminotransferase levels became normal or below two times the upper normal limit. Out of eight patients who completed the treatment, four were considered as responders but one of them, treated during five months, showed a relapse after three months. On the other hand, in one patient treated for twelve months, a persistent normalization of serum amino-transferases was observed: a liver biopsy showed a striking decrease of the inflammatory changes. As to the B-CH. 3 out of 8 patients who completed the treatment showed a disappearance of HBeAg and DNA-polymerase and were considered as responders. These preliminary results show that IFN-R is a promising drug but only multicenter controlled trials will establish its value in the treatment of viral chronic hepatitis.

Tratamiento de la hepatitis crónica viral / Treatment of chronic viral hepatitis

Gracias a los actuales conocimientos sobre la patogénesis de la hepatitis crónica viral y a la contemporánea disponibilidad de un amplio espectro de fármacos capaces de modular el sistema inmunitario y de interferir en la replicación viral, es hoy posible plantear una estrategia terapéutica más eficaz con respecto al esquema empírico y desilusionante del pasado. Se destaca la importancia del diagnóstico etiológico de la infección viral y del daño hepático para la elección del tratamiento más apropiado para cada uno de los pacientes, considerando los factores que favorecen o desfavorecen una buena respuesta terapéutica. Entre los fármacos disponibles el Interferon ha demostrado la mayor eficacia, pero su empleo es limitado a un grupo particular de pacientes. Tratamientos combinados han dado resultados interesantes en este último tiempo en pacientes refractarios al Interferon Alfa