Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable or metastatic melanoma with BRAF V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate the efficacy and safety of dabrafenib plus trametinib (dabrafenib-trametinib) with those of other therapeutic alternatives in the treatment of patients with BRAF V600 mutation unresectable or metastatic melanoma. The search was carried out on four databases up to July-2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF V600 mutation (NMA-pBRAFV600) and another with a mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via sensitivity analysis. Five clinical trials were included in the NMA-pBRAFV600. In the NMA-pBRAFV600 population, dabrafenib-trametinib had a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine, and on partial response rate (PRR) and overall response rate (ORR) compared with dacarbazine and vemurafenib. In the NMA-pMixed population, dabrafenib-trametinib had a positive effect on OS vs ipilimumab 3 mg/kg and on PFS and PRR vs ipilimumab (3 and 10 mg/kg), nivolumab, and pembrolizumab. However, dabrafenib-trametinib, and vemurafenib-cobimetinib were comparable in terms of clinical efficacy. In addition, dabrafenib-trametinib was associated with less grades 3 and 4 adverse events.

Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis.

The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF-V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF-V600 mutation (NMA-pBRAFV600) and another with mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA-pBRAFV600. Dabrafenib-trametinib was found to have a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA-pMixed, dabrafenib-trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib-trametinib and vemurafenib-cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events.

A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the Zika virus outbreak in Cúcuta, Colombia.

We have focused on the epidemiology and immunobiology of Zika virus (ZIKV) infection and factors associated with the development of Guillain-Barré syndrome (GBS) and other neurological syndromes in Cúcuta, the capital of North Santander department, Colombia. Data of patients with ZIKV disease reported to the national population-based surveillance system were used to calculate the basic reproduction number (R0) and the attack rates (ARs) as well as to develop epidemiological maps. Patients with neurological syndromes were contacted and their diagnoses were confirmed. A case-control study in which 29 patients with GBS associated with ZIKV compared with 74-matched control patients with ZIKV infection alone was undertaken. Antibodies against arboviruses and other infections that may trigger GBS were evaluated. The estimated value of R0 ranged between 2.68 (95% CI 2.54-2.67) to 4.57 (95% CI 4.18-5.01). The sex-specific ARs were 1306 per 100,000 females, and 552 per 100,000 males. A non-linear interaction between age and gender on the ARs was observed. The incidence of GBS in Cúcuta increased 4.41 times secondary to ZIKV infection. The lag time between ZIKV infection and neurological symptoms was 7 days (interquartile range 2-14.5). Patients with GBS appeared to represent a lower socioeconomic status and were living near to environmentally contaminated areas. All GBS patients were positive for IgG antibodies against both ZIKV and Dengue virus, and 69% were positive for Chikungunya virus. Noteworthy, GBS was associated with a previous infection with M. pneumoniae (OR: 3.95; 95% CI 1.44-13.01; p = 0.006). No differences in antibody levels against C. jejuni, Epstein-Barr virus and cytomegalovirus were observed. High rates of cranial nerves involvement and dysautonomia were present in 82% and 75.9%, respectively. Intensive care unit (ICU) admission was necessary in 69% of the GBS patients. Most of the patients disclosed a high disability condition (Hughes grade 4). Dysautonomia was the main risk factor of poor GBS prognosis (i.e., ICU admission and disability). Thirteen patients were diagnosed with other neurological syndromes different to GBS (6 with transverse myelitis, 3 with encephalitis, 3 with peripheral facial palsy and one with thoraco-lumbosacral myelopathy). Our data confirm an increased transmission of ZIKV in Cúcuta, and provide support to the view that severe neurological syndromes are related to ZIKV disease. The complex ways by which previous infections and socioeconomic status interact to increase the risk of GBS in people infected by ZIKV should be further investigated.

Natalizumab in patients with multiple sclerosis in Colombia: a case series / Natalizumab en pacientes con esclerosis múltiple en Colombia: una serie de casos

SUMMARY INTRODUCTION: Natalizumab is a humanized monoclonal antibody prescribed in the treatment of multiple sclerosis, the most prevalent chronic and inflammatory disease of the central nervous system (CNS). NEDA (no evidence of disease activity) status is the goal of multiple sclerosis treatment. METHODOLOGY: The clinical records of 22 patients with multiple sclerosis, followed for a mean of 9.2 years (range: 1.9 -18.3 years) between 2000 and 2018 were analyzed. These patients received treatment with natalizumab in a high-complexity neurological outpatient clinic in Bogotá, Colombia. RESULTS: Eighteen patients (82%) reached NEDA status within a median time of six months. Seven patients (32%) tested positive for anti-JC virus antibodies. However, none of them developed progressive multifocal leukoencephalopathy. During the evaluation period, five patients (23%) presented new lesions and 17 patients (77%) had relapses before reaching NEDA status. CONCLUSIONS: This study gave an exploratory analysis of the characteristics of a series of patients with MS in the Colombian context. In the retrospective analysis, it was observed that more than 80% of the studied sample that received treatment with natalizumab, reached NEDA status. Despite the methodological limitations inherent to this type of study and sample size, it suggests that natalizumab could be an appropriate medication for the management of multiple sclerosis in Colombia.

RESUMEN INTRODUCCIÓN: Natalizumab es un anticuerpo monoclonal humanizado empleado en el tratamiento de esclerosis múltiple, la enfermedad crónica e inflamatoria más prevalente del sistema nervioso central. El estado de NEDA (sin evidencia de actividad de la enfermedad) es el objetivo del tratamiento de la esclerosis múltiple. METODOLOGÍA: Se analizaron las historias clínicas de 22 pacientes con esclerosis múltiple que fueron seguidos durante una media de 9,2 años (rango: 1,9-18,3 años) entre 2000 y 2018. Estos pacientes recibieron tratamiento con natalizumab en una clínica ambulatoria neurológica de alta complejidad en Bogotá, Colombia. RESULTADOS: Dieciocho pacientes (82)% alcanzaron el estado NEDA en un tiempo medio de seis meses. Siete pacientes (32%) dieron positivo para anticuerpos anti-virus JC. Sin embargo, ninguno desarrolló leucoencefalopatía multifocal progresiva. Durante el periodo de seguimiento cinco pacientes (23%) presentaron nuevas lesiones y 17 pacientes (77%) tuvieron recaídas antes de alcanzar el estado NEDA. CONCLUSIONES: Este estudio provee un análisis exploratorio de las características de una serie de pacientes colombianos con esclerosis múltiple.. En el análisis retrospectivo, se observó que más de 80% de ellos alcanzó el estado NEDA. A pesar de las limitaciones metodológicas inherentes al tipo de estudio y el tamaño de la muestra, este estudio sugiere que natalizumab podría ser un medicamento apropiado para el tratamiento de la esclerosis múltiple. en Colombia.