Análisis de costo efectividad de everolimusmás ciclosporina y prednisona comparado con micofenolato más ciclosporina y prednisona para la inmunosupresión de mantenimiento en eltrasplantecardíacoen Colombia / Cost-effectiveness analysis of everolimusmás ciclosporin and prednisone compared to mycophenolate plus ciclosporin and prednisone for maintenance immunosuppression in the cardiac transplant in Colombia

Problema de investigación: Calcular los costos y la efectividad esperados de everolimus más ciclosporina y corticosteroide (ECC) comparado con micofenolato más ciclosporina y corticoesteroide (MCC) para el tratamiento de pacientes colombianos, adultos, receptores de trasplante de corazón por primera vez, que han iniciado la terapia de inducción de inmunosupresión y que se perfilan para el tratamiento de mantenimiento. Tipo de evaluación económica Análisis de costo-efectividad. Población objetivo: Pacientes colombianos, adultos, receptores de trasplante de corazón por primera vez, que han iniciado la terapia de inducción de inmunosupresión y que se perfilan para el tratamiento de mantenimiento. Intervención y comparadores I: Everolimus más ciclosporina (dosis reducida) y corticosteroide (ECC). C: Micofenolato más ciclosporina (dosis estándar) y corticoesteroides (MCC). Horizonte temporal: Vital. Perspectiva Sistema General de Seguridad Social en Salud (SGSSS). Tasa de descuento: Se emplea una tasa de descuento común tanto para los costos como para los desenlaces en salud equivalente al 5 % anual. Adicionalmente, se realizan análisis de sensibilidad de 0 %, 3,5 %, 7 % y 12 %. Estructura del modelo: Modelo de Markov anidado en un árbol de decisiones. Fuentes de datos de efectividad y seguridad: Fueron empleados los recursos siguientes: el Reporte de efectividad y seguridad de las alternativas a evaluar previamente publicado por el IETS, los resultados de una búsqueda de literatura económica en las bases de datos del CRD y los de una búsqueda manual de literatura económica y clínica, además de la información obtenida en la consulta a expertos clínicos. Desenlaces y valoración: Años de vida ganados. Desenlaces y valoración: Años de vida ganados. Costos incluidos: Costos directos de atención: Costos de medicamentos, Costos de procedimiento. Fuentes de datos de costos SISMED: Medicamentos Manual tarifario ISS 2001: Procedimientos. Resultados del caso base: La administración del esquema ECC como inmunosupresión de mantenimiento para pacientes receptores de trasplante es una estrategia más costosa y menos efectiva, respecto al esquema MCC por lo que se considera una estrategia dominada. Análisis de sensibilidad: La intervención ECC deja de ser dominada sólo cuando la probabilidad de muerte en rechazo agudo con la otra estrategia es del 8,70% o superior, y cuando la probabilidad de presentar rechazo agudo es de 7,88% o inferior; el costo de la atención de los eventos adversos crónicos para la estrategia MCC y el costo del esquema EEC, son las variables respecto a las cuales el costo total \r\nparece tener mayor sensibilidad. La curva de aceptabilidad muestra que para el umbral considerado de 3 veces el PIB per cápita, el esquema con everolimus tiene una probabilidad de ser costo efectiva del 15,6%.\r\nConclusiones y discusión: En la práctica clínica actual, everolimus se administra como componente de los esquemas de inmunosupresión de mantenimiento sólo en situaciones particulares tales como terapia escalada en inmunosupresión (en caso de rechazo con terapia estándar), vasculopatía del injerto, disfunción renal o neoplasias. El esquema más usado en la práctica asistencial actual es el que incluye micofenolato más ciclosporina y prednisona (un corticosteroide), que es el indicado para todos los pacientes trasplantados. Los estudios clínicos desarrollados que han comparado estos dos esquemas \r\nconcluyen que tienen un perfil semejante de efectividad y seguridad y el acá desarrollado clasifica el esquema con everolimus como una estrategia dominada.(AU)

Análisis de costo efectividad de everolimus más ciclosporina y prednisona comparado con micofenolato más ciclosporina y prednisona para la inmunosupresión de mantenimiento en el trasplante renal en Colombia / Cost-effectiveness analysis of everolimus plus ciclosporin and prednisone compared to mycophenolate plus ciclosporin and prednisone for maintenance immunosuppression in renal transplantation in Colombia

Problema de investigación: Calcular los costos y la efectividad esperados del everolimus mas ciclosporina y corticosteroide (ECC) comparado con micofenolato mas ciclosporina y corticoesteroides (MCC) para el tratamiento de pacientes colombianos, adultos, receptores de trasplante de riñón por primera vez, que han iniciado la terapia de inducción de inmunosupresión y que se perfilan para el tratamiento de mantenimiento. Tipo de evaluación económica: Análisis de costo-efectividad. Población objetivo: Pacientes colombianos, adultos, receptores de trasplante de riñón por primera vez, que han iniciado la terapia de inducción de inmunosupresión y que se perfilan para el tratamiento de mantenimiento. Intervención y comparadores: I: Everolimus mas Ciclosporina (dosis reducida) y Corticosteroide (ECC). C: Micofenolato mas Ciclosporina (dosis estándar) y Corticoesteroides (MCC). Horizonte temporal: Vital. Perspectiva: Sistema General de Seguridad Social en Salud (SGSSS). Tasa de descuento: Se emplea una tasa de descuento común tanto a los costos como a los desenlaces en salud, equivalente al 5 % anual. Adicionalmente, se realizan análisis de sensibilidad de 0 %, 3,5 %, 7 % y 12 %. Estructura del modelo: Modelo de Markov anidado en un árbol de decisiones. Fuentes de datos de efectividad y seguridad. Fueron usados los recursos siguientes: el Reporte de efectividad y seguridad de las alternativas a evaluar previamente publicado por el IETS, los resultados de una búsqueda de literatura económica en las base de datos del CRD, de una búsqueda manual de literatura económica y clínica, y la información obtenida producto de la consulta a expertos clínicos. Desenlaces y\r\nvaloración: Años de vida ganados. Costos incluidos: Costos directos de atención: Costos de medicamentos\r\nCostos de procedimientos. Fuentes de datos de costos: SISMED: Medicamentos Manual tarifario ISS 2001: Procedimientos. Resultados del caso base: Los resultados del caso base para la administración del esquema ECC como inmunosupresión de mantenimiento para pacientes receptores de trasplante es una estrategia más costosa y más efectiva, respecto al esquema MCC; no obstante, si se asume que la disposición a pagar es 3 veces el PIB per cápita por un años de vida ganado, la estrategia ECC no es costo efectiva por superar dicho umbral. Análisis de sensibilidad: Este resultado se mantiene en todos los escenarios planteados excepto para los casos en los cuales la probabilidad de pérdida del injerto ante presencia de rechazo agudo en el esquema MCC toma valores superiores al 8%, cuando los costos del esquema de medicamentos ECC son inferiores a $4.083.749, y cuando la probabilidad de presentar eventos adversos crónicos con la estrategia ECC es inferior al 25%. Conclusiones y discusión: En la práctica clínica actual, everolimus se administra como componente de los esquemas de inmunosupresión de mantenimiento sólo en situaciones particulares como estrategia de conversión si se presenta toxicidad renal por ciclosporina, cáncer de piel u otro tipo de cáncer que se encuentra en riesgo de aumentar su tasa de crecimiento, o ante eventos como la hiperplasia gingival entre los más comunes. El esquema más usado en la práctica asistencial actual es el que incluye micofenolato más ciclosporina y prednisona, indicado para todos los pacientes trasplantados. Los estudios clínicos desarrollados que han comparado estos dos esquemas concluyen que tienen un perfil semejante de efectividad y seguridad y el acá desarrollado clasifica el esquema con everolimus como una estrategia no costo efectiva.

Análisis de impacto presupuestal de everolimus más ciclosporina y prednisona comparado con micofenolato más ciclosporina y prednisona para la profilaxis del rechazo en los receptores de trasplante de corazón en Colombia / Budget impact analysis of everolimus plus ciclosporin and prednisone compared to mycophenolate plus ciclosporin and prednisone for rejection prophylaxis in heart transplant recipients in Colombia

Tecnologías evaluadas: Intervención: e verolimus más ciclosporina y corticoesteroide en pacientes con trasplante de corazón. Comparador: micofenolato más ciclosporina y prednisona. Población: Adultos receptor es trasplante de corazón por primera vez. Perspectiva: ercer pagador, que en el caso colombiano corresponde al Sistema General de Seguridad Social en Salud (SGSSS). Horizonte temporal: El horizonte temporal de este AIP en el caso base corresponde a un año. Adicionalmente se reportan las estimaciones del impacto presupuestal para los años 2 y 3, bajo el supuesto de la inclusión en el POS en el año 1. Costos incluidos: Costos de los medicamentos incluidos en la terapia de mantenimiento. Fuente de costos: SISMED. Escenarios: Se realizaron análisis de escenarios que contemplaron una tasa de inserción del nuevo tratamiento inferior al 100% como terapia de conversión más no de tratamiento de primera línea y diferentes tasas de crecimiento para los años 2 y 3. Resultados: En un escenario con tasa de inserción del 100% del nuevo tratamiento, el impacto resupuestal es de $1.492.857.500,75 para el año 1.(AU)

Effects of immunosuppression with tacrolimus and mycophenolate mofetil on renal histology and function in single kidney rats submitted to ischemia and reperfusion

PURPOSE: To evaluate renal histological changes and renal function in single kidney rats submitted to renal ischemia-reperfusion and to immunosuppression with tacrolimus and mycophenolate-mofetil. METHODS: Experimental study with 80 Wistar rats distributed into control, Sham and six other groups treated with immunosuppressive drugs. Animals undergoing surgery, right nephrectomy and left renal clamping, killed on the 14th day and analyzed for renal histology, urea and creatinine. RESULTS: The group receiving tacrolimus at higher doses (T3) showed renal histological lesions indicative of early nephrotoxicity, and significant increase in urea and creatinine. The group M (mycophenolate-mofetil alone) and the group M2 (mycophenolate-mofetil combined with half the usual dose of tacrolimus) presented a slight rise in serum urea. The groups using mycophenolate-mofetil alone or combined with tacrolimus showed creatinine levels similar to that of the group T3. CONCLUSIONS: Histologically, the association of injury by ischemia-reperfusion with the use of tacrolimus or mycophenolate-mofetil alone demonstrated a higher rate of renal changes typical of early nephrotoxicity. In laboratory, the combination of injury by ischemia-reperfusion with tacrolimus at higher doses proved to be nephrotoxic. .

Evaluación de efectividad y seguridad de everolimus más ciclosporina y esteroides o everolimus más tacrolimus y esteroide comparado con ciclosporina más micofenolato y esteroides, tacrolimus más micofenolato y esteroides, sirolimus con micofenolato y esteroides, en pacientes receptores de trasplante de riñón, hígado y corazón / Efficacy and safety assessment of everolimus plus ciclosporin and steroids or everolimus plus tacrolimus and steroid compared to cyclosporine plus mycophenolate and steroids, tacrolimus plus mycophenolate and steroids, sirolimus with mycophenolate

Introducción: Everolimus es un medicamento perteneciente a un grupo de inmunosupresores selectivos que inhiben la vía del m- TOR (mammalian target of rapamycin) y es empleado para evitar el rechazo de trasplante de órganos sólidos. Esta evaluación tecnológica se desarrolló en el marco de la actualización integral del Plan Obligatorio de Salud para el año 2015. Objetivo: Evaluar la efectividad y seguridad del uso de everolimus más ciclosporina y esteroides o everolimus más tacrolimus y esteroide comparado con ciclosporina más micofenolato y esteroides, tacrolimus más micofenolato y esteroides, sirolimus con micofenolato y esteroides, en pacientes receptores de trasplante de riñón, hígado y corazón. Metodología: La evaluación fue realizada de acuerdo con un protocolo definido a priori por el grupo desarrollador. Se realizó una búsqueda sistemática en MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects y LILACS, con restricción al idioma inglés y español y limitada a revisiones sistemáticas publicadas en los últimos cinco años y ensayos clínicos sin restricción de tiempo. Las búsquedas electrónicas fueron hechas entre octubre y diciembre de 2014 y se complementaron mediante búsqueda manual en bola de nieve y una consulta con expertos temáticos. La tamización de referencias se realizó por un revisor. La selección de estudios fue realizada mediante la revisión en texto completo de las referencias preseleccionadas, verificando los criterios de elegibilidad. La calidad de los estudios fue valorada con la herramienta de riesgo de sesgo de la Colaboración Cochrane. Las características de los estudios fueron extraídas a partir de las publicaciones originales. Se realizó una síntesis narrativa de las estimaciones del efecto para las comparaciones y desenlaces de interés a partir de los estudios de mejor calidad. Se estimaron medidas combinadas del efecto a través de un metanálisis con el método de Mantel-Haenszel y un modelo de efectos aleatorios, empleando el programa RevMan 5.2. Resultados: Everolimus, en terapia combinada con ciclosporina o tacrolimus presenta un perfil semejante a su comparador micofenolato en terapia combinada en los desenlaces supervivencia del injerto al año (para riñón RR=1.00 IC95% 0.97, 1.01), para hígado p=0.50 y para corazón RR=1.0, IC95% 0.98, 1.02) y supervivencia del paciente al año (para riñón RR=0.99 IC95% 0.97, 1.01, para hígado p=0.60 y para corazón RR=0.97 IC95% 0.94, 1.01), pues no se encontraron diferencias con significancia estadística en ninguno de estos desenlaces. En relación al desenlace rechazo agudo en el primer año en trasplante de riñón y corazón se desempeña de manera semejante everolimus más CyA más PRED comparado con micofenolato con igual combinación. En trasplante de hígado al comparar everolimus más tacrólimus a dosis baja más PRED se desempeña mejor que everolimus más tacrólimus a dosis estándar en el mismo desenlace (p=0.003). Al evaluar la función renal al año everolimus más CyA más PRED se comporta de manera semejante a micofenolato con igual combinación en pacientes receptores de trasplante renal, sin embargo en los pacientes receptores de trasplante de corazón es mejor everolimus en conservar la función renal (RR= -4.86, IC95% -8.68, -1.04). En receptores de trasplante de hígado tiene mejor desempeño everolimus más TAC a dosis baja más esteroide comparado con EVE más TAC a dosis estándar más esteroide pues conserva mejor la función renal a los doce meses (80.9±27.3 vs 70.3±23.1, p<0.0001). En relación a seguridad everolimus, en terapia combinada presenta un perfil semejante a micofenolato, en la presentación de eventos adversos de manera global, malignidad, diabetes de novo, diarrea y temblor. El evento adverso infección por citomegalovirus en el primer año fue menor en los pacientes que recibieron everolimus. Los eventos adversos edema periférico, hiperlipidemia y anemia fueron más frecuentes en los pacientes del grupo de everolimus. Además everolimus tiene efecto protector sobre el evento vasculopatía del trasplante cardíaco (RR=0.47 IC95% 0.25, 0.89).\r\nEn receptores de trasplante de hígado se presentaron en mayor proporción los eventos adversos edema periférico e hiperlipidemia los 24 meses (p<0,0001) con EVE más TAC a dosis baja más PRED al compararlo con EVE más TAC dosis estándar. Los eventos adversos edema periférico e hiperlipidemia a los 24 meses (p<0.0001) son más frecuentes con EVE mas TAC a dosis baja. No se encontraron diferencias para los eventos adversos diarrea, anemia y proteinuria. Conclusiones: En pacientes receptores de trasplante de riñón, hígado y corazón everolimus en terapia combinada con ciclosporina y esteroide tiene un perfil semejante de efectividad y seguridad que el micofenolato en terapia combinada, excepto en los desenlaces rechazo del trasplante de hígado a un año y función renal al año en el que everolimus es mejor, además de que tener una menor proporción de infección por citomegalovirus al año.(AU)

Refractory pemphigus vulgaris treated with rituximab and mycophenolate mofetil

The main treatment for pemphigus vulgaris are systemic corticosteroids and immunosuppressive agents, but due to adverse reactions and therapeutic failure, new drugs such as rituximab and mycophenolate mofetil have been used. In this case report are described two cases of severe pemphigus vulgaris refractory to various treatments, with resolution after use of rituximab and mycophenolate mofetil, associated with corticosteroids. A higher-than-usual dose of rituximab was employed, without the occurrence of serious adverse reactions. Mycophenolate mofetil was added as adjunctive therapy due to lack of response to azathioprine.

Qualitative analysis of the deposit of collagen in bladder suture of rats treated with tacrolimus combined with mycophenolate-mofetil

PurposeTo evaluate the synthesis of type I (mature) and type III (immature) collagen in bladder suture of rats treated with a combination of tacrolimus and mycophenolate mofetil for 15 days.Materials and MethodsThirty rats were divided into 3 groups: the sham, control and experimental groups. All the animals underwent laparotomy, cystotomy and bladder suture in two planes with surgical PDS 5-0 thread. The sham group did not receive treatment. The control group received saline solution, and the experimental group received 0.1mg/kg/day of tacrolimus with 20mg/kg/day of mycophenolate mofetil, for 15 days. From then on, the tacrolimus was dosed. The surgical specimens of the bladder suture area were processed so that the total type I and type III collagen could be measured by the picrosirius red technique.ResultsThere was a predominance of type I collagen production in the sham and control groups compared to the experimental group, in which type III collagen was predominant. The production of total collagen did not change.ConclusionThe association of tacrolimus and mycophenolate mofetil in animals qualitatively changes the production of collagen after 15 days with a predominance of type III collagen.

Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience / Tratamento com imunossupressores em crianças com síndrome nefrótica resistente a corticosteróide: experiência de um único centro

INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

INTRODUÇÃO: A síndrome nefrótica é uma das mais frequentes doenças glomerulares em crianças e o tratamento com corticosteróides ainda é o tratamento de escolha. Apesar disso, 10 a 15% dos pacientes são resistentes a corticosteróides, e o melhor tratamento para tais casos ainda não foi definido. O ácido micofenólico (AM) é um dos tratamentos usados em tais situações. OBJETIVO: Descrever o comportamento clínico de crianças diagnosticadas com síndrome nefrótica resistente a corticosteróide (SNRC) e avaliar a resposta terapêutica ao AM. MÉTODOS: Esse foi um estudo retrospectivo e descritivo. RESULTADOS: 26 registros de pacientes com SNRC; 70% homens e 30% mulheres. Todos os pacientes foram submetidos a biópsias renais, o que mostrou predominância de glomeruloesclerose segmentar focal (GESF). Os medicamentos imunossupressores utilizados foram: Mofetil Micofenolato (MMF) 100%; Ciclosporina 69,2%; Ciclosfosfamida 23,1%; e Rituximabe 23%. Um mês após início do tratamento com MMF, 61,5% tiveram remissão. A mediana das recidivas por ano para os pacientes foi de 3 (p25: 2,75 - p75: 4). Essa mediana se tornou 1 (p25: 1 - p75: 3,25) após o uso da medicação (p = 0,08). Além disso, antes do início do tratamento com MMF, a mediana da dose de corticosteróide foi de 1 (p25: 0.5 - p75: 1.62) mg/k/ dia. Após a utilização do MMF, essa mediana se tornou 0,07 (p25: 0 - p75: 0,55) mg/k/dia (p < 0,001), em 8 pacientes a prednisolona foi interrompida. CONCLUSÃO: em nossa casuística, o tratamento com MMF mostrou resultados positivos, tais como a redução na frequência de recidivas, menos proteinúria, e redução da dose de corticosteróide administrada sem deterioração nas taxas de filtração glomerular. Entretanto, mais estudos são necessários para se avaliar a eficácia, segurança e otimização da dosagem.

Two Cases of Refractory Thrombocytopenia in Systemic Lupus Erythematosus that Responded to Intravenous Low-Dose Cyclophosphamide

Treatment of thrombocytopenia in systemic lupus erythematosus (SLE) is considered in cases of current bleeding, severe bruising, or a platelet count below 50,000/microliter. Corticosteroid is the first choice of medication for inducing remission, and immunosuppressive agents can be added when thrombocytopenia is refractory to corticosteroid or recurs despite it. We presented two SLE patients with thrombocytopenia who successfully induced remission after intravenous administration of low-dose cyclophosphamide (CYC) (500 mg fixed dose, biweekly for 3 months), followed by azathioprine (AZA) or mycophenolate mofetil (MMF). Both patients developed severe thrombocytopenia in SLE that did not respond to pulsed methylprednisolone therapy, and started the intravenous low-dose CYC therapy. In case 1, the platelet count increased to 50,000/microliter after the first CYC infusion, and remission was maintained with low dose prednisolone and AZA. The case 2 achieved remission after three cycles of CYC, and the remission continued with low dose prednisolone and MMF.

Micofenolato mofetil na síndrome de Sjögren primária: uma opção para o tratamento da agranulocitose / Mycophenolate mofetil in primary Sjögren's syndrome: a treatment option for agranulocytosis

A síndrome de Sjögren (SS) é uma doença autoimune caracterizada pela presença de infiltrado linfocítico nas glândulas salivares e lacrimais. Manifestações hematológicas da síndrome de Sjögren primária (SSp) geralmente consistem em anemia leve, trombocitopenia, neutropenia moderada e linfopenia. Agranulocitose é raramente descrita e, em geral, responde bem ao tratamento de imunossupressão. Neste trabalho, descrevemos o caso de uma paciente portadora de SSp que apresentou quadro de agranulocitose refratária ao tratamento. A biópsia de medula revelou medula óssea hipocelular com maturação normal da série granulocítica. A paciente foi sucessivamente tratada com prednisona em altas doses, fator estimulador de colônia de macrófagos e ciclosporina, todos sem resposta hematológica. Micofenolato mofetil (MMF) foi iniciado, e após dois meses houve aumento na contagem das células brancas. Após um ano de seguimento a paciente não apresentou novos episódios de neutropenia, nem complicações infecciosas. Concluímos que, na agranulocitose refratária associada à SSp, o tratamento com MMF pode ser uma opção eficaz e bem tolerada.

The Sjögren's syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of salivary and lacrimal glands. Hematological manifestations of primary SS (pSS) usually consist of mild anemia, thrombocytopenia, moderate neutropenia, and lymphopenia. Agranulocytosis is rarely reported and usually responds to immunosuppression. We report the case of a pSS patient who presented with refractory agranulocytosis. Bone marrow biopsy disclosed a hypocellular bone marrow with normal maturation of the granulocytic series. The patient was successively treated with high-dose prednisone, granulocyte-macrophage colony stimulation factor, and cyclosporine, with no hematological response. Mycophenolate mofetil (MMF) was initiated and after two months there was a rise on the white blood cell count. After one year of follow-up, she had neither further neutropenia episodes, nor infectious complications. We conclude that, in pSS refractory agranulocytosis, MMF can be an effective and well-tolerated treatment option.

Treatment of neuromyelitis optica: an evidence based review / Tratamento da neuromielite óptica: uma revisão baseada em evidências

Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.

Neuromielite óptica (NMO) é uma doença inflamatória do sistema nervoso central caracterizada por grave neurite óptica e mielite transversa, com um curso usualmente recorrente. O anticorpo contra aquaporina-4 é positivo em grande porcentagem dos pacientes com NMO e se liga a este canal de água altamente expresso nos processos pediosos dos astrócitos. Devido à gravidade dos ataques de NMO e ao elevado risco de incapacidade, o tratamento deve ser instituído tão logo o diagnostico seja confirmado. Existem evidências crescentes de que pacientes com NMO respondem de forma diferente dos pacientes com esclerose múltipla (EM) e, portanto, os tratamentos utilizados na EM podem não ser adequados para NMO. Os quadros agudos de NMO são tratados com pulsos de corticosteroides em altas doses e plasmaférese. O tratamento de manutenção também deve ser instituído para evitar ataques subsequentes e é baseado em corticosteroides orais em baixas doses ou imunossupressores, como a azatioprina e o micofenolato mofetil. Novas estratégias de tratamento utilizando anticorpos monoclonais como rituximab têm sido avaliadas para NMO, com resultados positivos em estudos abertos. Entretanto, não existem estudos clínicos controlados, randomizados, para confirmar a segurança e eficácia dos tratamentos atualmente utilizados na NMO.

A pilot study on area under curve of mycophenolic acid as a guide for its optimal use in renal transplant recipients.

Background & objectives: The immunosuppressants administered to renal transplant subjects are usually monitored therapeutically to prevent graft rejection and drug toxicity. Mycophenolic acid (MPA) is an immunosuppressant. The present prospective study was undertaken to establish the utility of plasma level monitoring of MPA and to correlate it with clinical outcomes in renal transplant receipients. Methods: MPA plasma level at 2, 4 and 9 h and the area under concentration-time curve (AUC) were estimated using high performance liquid chromatography in 24 renal transplant recipients receiving immunosuppressant MPA plus tacrolimus and steroid. Results: There was wide inter-individual variation in MPA plasma level and the AUC. The incidences of gastrointestinal adverse drug events (diarrhoea and acidity) were significantly more in the high MPA AUC patients. Though biopsy proven acute rejection was not found, of the six subjects with lower MPA AUC (<30 mg.h/l), three were clinically diagnosed to develop tacrolimus nephrotoxicity. The Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) scores represented better health related quality of life in lower MPA AUC than in the higher MPA AUC (>60 mg.h/l). Interpretation & conclusions: The present findings suggest the MPA AUC of 30 - 60 mg.h/l in the maintenance stage of renal transplant patients to have optimum clinical benefit and relegated adverse events profile indicating the usefulness of AUC of MPA with limited sampling strategy in optimizing its use.

Methimazole-Induced Bullous Systemic Lupus Erythematosus: A Case Report

Bullous systemic lupus erythematosus (SLE) is a kind of LE-non-specific bullous skin disease that is rarely induced by a medication. We describe the first case of bullous SLE to develop after administration of methimazole. A 31-yr-old woman presented with generalized erythematous patches, multiple bullae, arthralgia, fever, conjunctivitis, and hemolytic anemia. Biopsy of her bulla showed linear deposition of lgG, lgA, C3, fibrinogen, and C1q at dermo-epidermal junction. She was diagnosed as bullous SLE and treated with prednisolone, dapsone, hydroxychloroquine, and methotrexate. Our experience suggests that SLE should be considered as a differential diagnosis when bullous skin lesions develop in patients being treated for hyperthyroidism.

Prospective Controlled Protocol for Three Months Steroid Withdrawal with Tacrolimus, Basiliximab, and Mycophenolate Mofetil in Renal Transplant Recipients

During the past few years, new immunosuppressants, such as tacrolimus, mycophenolate mofetil (MMF) and basiliximab, have been shown to successfully decrease the incidence of acute rejection, possibly acting as potent substrates for safe steroid withdrawal. Therefore, clinical outcome of 3 months steroid withdrawal, while using the above immunosuppressants, was analyzed. Clinical trial registry No. was NCT 01550445. Thirty de novo renal transplant recipients were enrolled, and prednisolone was slowly withdrawn 3 months post-transplantation by 2.5 mg at every two weeks, until 8 weeks. During steroid withdrawal, 10 patients (30.0%) discontinued the protocol and they were maintained on steroid treatment. Among 20 steroid free patients, 8 patients (40.0%) re-started the steroid within 12 months post-transplantation. By the study endpoint, 12 (40%) recipients did not take steroid and survival of patients and grafts was 100%. In conclusion, in kidney transplant patients, 3 months steroid withdrawal while taking tacrolimus, basiliximab and mycophenolate mofetil was not associated with increased mortality or graft loss. Despite various causes of failure of steroid withdrawal during the follow-up period, it is a strategy well advised for kidney transplant recipients with regard to long-term steroid-related complications.

Prospective Controlled Protocol for Three Months Steroid Withdrawal with Tacrolimus, Basiliximab, and Mycophenolate Mofetil in Renal Transplant Recipients

During the past few years, new immunosuppressants, such as tacrolimus, mycophenolate mofetil (MMF) and basiliximab, have been shown to successfully decrease the incidence of acute rejection, possibly acting as potent substrates for safe steroid withdrawal. Therefore, clinical outcome of 3 months steroid withdrawal, while using the above immunosuppressants, was analyzed. Clinical trial registry No. was NCT 01550445. Thirty de novo renal transplant recipients were enrolled, and prednisolone was slowly withdrawn 3 months post-transplantation by 2.5 mg at every two weeks, until 8 weeks. During steroid withdrawal, 10 patients (30.0%) discontinued the protocol and they were maintained on steroid treatment. Among 20 steroid free patients, 8 patients (40.0%) re-started the steroid within 12 months post-transplantation. By the study endpoint, 12 (40%) recipients did not take steroid and survival of patients and grafts was 100%. In conclusion, in kidney transplant patients, 3 months steroid withdrawal while taking tacrolimus, basiliximab and mycophenolate mofetil was not associated with increased mortality or graft loss. Despite various causes of failure of steroid withdrawal during the follow-up period, it is a strategy well advised for kidney transplant recipients with regard to long-term steroid-related complications.

Dermatose por IgA e IgG linear: relato de caso com boa resposta terapêutica à dapsona e ao micofenolato mofetil / Linear IgA/IgG bullous dermatosis: successful treatment with dapsone and mycophenolate mofetil

Relata-se o caso de paciente feminina, de 21 anos, com dermatose por IgA e IgG linear. Inicialmente, a resposta clínica foi favorável à dapsona. Após a interrupção desta medicação, por crise de anemia sintomática, precipitada por malária, houve piora da doença, apesar da utilização da prednisona e pulsoterapia com metilprednisolona. A reintrodução da dapsona, associada ao micofenolato mofetil, possibilitou o controle da enfermidade.

A 21-year-old female presenting linear IgA and IgG disease initially responded well to dapsone therapy. However, the treatment with dapsone was withdrawn due to severe anemia induced by malaria, which led to worsening of the clinical picture. Although prednisone and methylprednisolone were tried, the patient responded only to the association of dapsone and mycophenolate mofetil.

Estudio de biodisponibilidad relativa entre dos formulaciones orales de micofenolato mofetilo en voluntarios sanos / Relative bioavailability study of two oral formulations of mycophenolate mofetil in healthy volunteers

Background: The bioequivalence of different formulations of a same pharmaceutical product must be tested empirically. Aim: To evaluate the relative bioavailability for an oralformulation of mycophenolate mofetil (MMF) (Linfonex™) compared to the reference formulation (Cellcept™) to determine the bioequivalence between both formulations. Material and Methods: A randomized, crossover, double-blind trial in 22 healthy male volunteers, who received a single oral dose of 1000 mg of Linfonex and Cellcept with a washout period of 10 days. Plasma levels of the drug were determined by high performance liquid chr ornatography. Plasma concentrations were plotted and maximum concentration, area under the plasma concentration versus time between 0 and 12 hours after administration and área under plasma concentration curve versus time after administration between 0 and infinity, were calculated for both products. Results: The active compound, mycophenolic acid, was similarly absorbed in both formulations. No statistically significant differences were found in calculated pharmacokinetic parameters between both formulations. Conclusions: Linfonex™ 500 mg is bioequivalent to Cellcept™ 500 mg.

Effects of mycophenolate sodium on mucociliary clearance using a bronchial section and anastomosis rodent model

OBJECTIVE: To study the effects of mycophenolate sodium on mucociliary clearance. INTRODUCTION: Mycophenolate is one of the most commonly used immunosuppressive drugs in lung transplantation. Although its pharmacokinetic properties are well defined, its side effects on mucociliary clearance have not yet been studied. METHODS: Sixty rats were subjected to left bronchial section and anastomosis. The right bronchus was used as a control. After surgery, the rats were assigned to two groups based on whether they received saline solution (n = 30) or mycophenolate sodium (n = 30). After 7, 15, or 30 days of treatment, 10 animals from each group were sacrificed, and in vitro mucus transportability, in situ mucociliary transport velocity and ciliary beat frequency were measured. RESULTS: The analysis of mucus transportability revealed that neither mycophenolate nor bronchial section altered any transportability related property for up to 30 days of treatment after surgery (p>0.05). With regard to ciliary beat frequency, the operated left bronchi from the mycophenolate group showed a significant decrease on post-surgical day 30 (p = 0.003). In addition, we found a significant reduction in the in situ mucociliary transport velocity in the mycophenolate-treated group (p = 0.0001). DISCUSSION: These data add important information regarding mucociliary clearance dysfunction following mycophenolate therapy and suggest that mycophenolate might contribute to the high incidence of respiratory tract infections in lung transplant patients. Further studies are needed to investigate the combined action of mycophenolate with other immunosuppressive drugs and to establish methods to protect and recover mucociliary clearance, an important airway defense mechanism.

Outcomes of late corticosteroid withdrawal after renal transplantation in patients exposed to tacrolimus and/or mycophenolate mofetil: meta-analysis of randomized controlled trials

Corticosteroids are increasingly used in renal transplant patients to minimize organ rejection after transplantation. In attempts to reduce corticosteroids adverse effects, transplant professionals are customary attempted to taper off, and permanently stop corticosteroids after few months of administration with other immunosuppressants. To evaluate clinical benefits and risks of late corticosteroid withdrawal in renal transplant patients treated with tacrolimus [TAC] or mycophenolate mofetil [MMF], or both. A meta-analysis was performed of published randomized controlled trials that reported outcomes in kidney transplant patients who were randomized to corticosteroids maintenance or late withdrawal under concomitant immunosuppression by TAC, MMF or both. Outcomes included acute graft rejection; graft failure rate; all-cause mortality; incidence of post-transplant diabetes; change in serum creatinine and total cholesterol; and change in pediatric standardized height z-score. PubMed and Google Scholar were used in literature search between 1999 and April 1, 2010. Data were combined using unweighted random effects model. Nine studies randomized 1907 patients met the inclusion criteria: TAC [n=1]; MMF [n=6]; both [n=2]. Compared to maintenance therapy, late corticosteroid withdrawal was associated with 34% increase in the risk of acute graft rejection [95% CI for OR: 0.47-3.82]; 35% and 5% reductions in the risk of graft failure and patient's all-cause mortality [95% CI for OR: 0.26-1.60; 0.23-3.93, respectively]; and 4% increase in post-transplant diabetes risk [95% CI for OR: 0.45-2.41]. Late corticosteroid withdrawal was associated with substantial reduction in total cholesterol levels [mean difference: 18.1 mg/dL; 95% CI: 7.1-29.0 mg/dL], but did not reduce serum creatinine levels [-0.00 mg/dL; 95% CI: -0.17 to 0.17]. Stopping corticosteroids was associated with better pediatric growth outcomes. Late corticosteroid withdrawal under TAC and/or MMF-lead immunosuppression after kidney transplantation could provide benefits in terms of total cholesterol, patient and graft survival, and pediatric growth. This strategy, however did not reduce the risk of acute graft rejection, post-transplant diabetes mellitus, and deterioration in serum creatinine levels

A Case of Minimal Change Disease Treated Successfully with Mycophenolate Mofetil in a Patient with Systemic Lupus Erythematosus

The World Health Organization classifies lupus nephritis as class I to V or VI. However, a few cases of minimal change glomerulopathy have been reported in association with systemic lupus erythematosus (SLE). Mycophenolate mofetil has been shown to be effective for treatment of minimal change disease and lupus nephritis. A 24-year-old woman diagnosed with SLE five years prior to presentation complained of a mild generalized edema. The urinalysis showed microscopic hematuria and proteinuria. The assessed amount of total proteinuria was 1,618 mg/24 hours. A renal biopsy demonstrated diffuse fusion of the foot processes of podocytes on electron microscopy. Mycophenolate mofetil was started in addition to the maintenance medications of prednisolone 10 mg/day and hydroxychloroquine 400 mg/day. After six months of treatment, the microscopic hematuria and proteinuria resolved, and the total urine protein decreased to 100 mg/24 hours.