Práctica clínica en prevención de migraña con anticuerpos monoclonales del péptido relacionado con el gen calcitonina: evidencias de casos reales / Clinical practice in prevention of migraine with calcitonin-gene related peptide monoclonal antibodies: real-world evidence

Introducción: Los anticuerpos monoclonales (mAbs) del péptido relacionado con el gen de la calcitonina (CGRP) son un novedoso tratamiento para prevenir la migraña crónica y la episódica de alta frecuencia. Método: Se realizó un estudio observacional, retrospectivo, multicéntrico para analizar la efectividad y seguridad de los mAbs anti-CGRP (erenumab, galcanezumab, fremanezumab). La variable de efectividad fue la reducción en los días de migraña al mes (MMDs). La seguridad se midió con los efectos adversos descritos. Resultados: Los resultados de 127 pacientes muestran efectividad similar entre erenumab y galcanezumab en la reducción de los MMDs. Una proporción importante de pacientes cambió de mAb por pérdida de respuesta o fallo primario tras una media de 7 meses: 15,11% erenumab; 24% galcanezumab. Algunos pacientes se trataron con-comitantemente con toxina botulínica A: 8,13% erenumab; 12% galcanezumab; 6,25% fremanezumab. Más del 60% de pacientes habían sido tratados previamente con toxina botulínica A con falta de respuesta tras varias dosis. Se describieron efectos adversos cardiovasculares (dolor en el pecho, taquicardia) exclusivamente en pacientes con erenumab. Conclusiones: La práctica clínica actual se basa en el intercambio de mABs anti-CGRP en casos de falta de respuesta o migraña refractaria, aunque su evidencia es limitada y se ha demostrado que la efectividad entre los tres fármacos es equivalente. Las Agencias Reguladoras recomiendan un período de 12 semanas para evaluar la efectividad del mAb. La mitad de los pacientes refirieron falta de seguimiento por Neurología. Los farmacéuticos clínicos son nece-sarios en la atención integrada de la migraña. (AU)

Introduction: Calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are novel therapeutic option for prevention of chronic migraine (CM) and high-frequency episodic migraine (HFEM). Method: An observational, retrospective, multicentre, real-world evidence study was developed to analyse the ef-fectiveness and safety of anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab). Effectiveness was measured by monthly migraine days (MMDs) reduction. Adverse events were recorded for safety outcome. Results: Results from 127 patients showed similar effectiveness between erenumab and galcanezumab in MMDs reduction. A notable proportion of patients switched of mAb because of loss of response or primary no-response after seven months: 15.11% erenumab; 24% galcanezumab. Some patients were concomitant treated with Onabot-ulinumtoxin A (Onabot A): 8.13% erenumab; 12% galcanezumab; 6.25% fremanezumab. More than 60% of the total were previously treated with Onabot A with loss of response. Cardiovascular adverse events are exclusively reported by erenumab group (chest pain, tachycardia). Conclusions: Current clinical practice is based on switching of CGRP mAbs after loss of response or refractory mi-graine, even though evidence for this practice is limited and effectiveness between the drugs has been demonstrat-ed to be equivalent. The period of 12 weeks since the first dose of the CGRP mAb, recommended by Regulatory Agencies, should be respected to determine if the mAb selected is being ineffective. At least, half of the patients complained about lack of follow-up by reference neurologist. Clinical pharmacists are important to help these pa-tients manage the burden of migraine. (AU)

Fumarase deficiency: a difficult diagnosis and a challenging treatment approach

Introduction: Fumarase deficiency is a rare autosomal metabolic disease that curse with hypotonia, hyperlacticaemia and seizures. Diagnosis based in laboratory test might be done carefully, as most of metabolic diseases present similar symptomatology: hypotony, convulsions, lactic and pyruvic acidemia. Method: The objective is to analyse the pharmacological and nutritional approach of a neonate who presented symptoms of metabolic congenital disorders.Results:The patient is a three-month girl with heterozygote mutation in fumarase gene, who presented clinical manifestations of the altered enzyme function. She presented hyperlacticaemia, organic aciduria and alterations of amino acid levels. First diagnosis suspected was pyruvate dehydrogenase deficiency, so nutritional treatment with ketogenic diet was initiated. After medical discharge, she was hospitalized in emergency basis with cardiac arrest and metabolic decompensation. Genetic test revealed a heterozygote mutation in fumarase. Clinical symptomatology could have worsened because of the difficult diagnosis. Conclusions: Nutritional and pharmacological treatment of fumarase deficiency is considered essential for the patient’s evolution, but further researchers must be carried out to profoundly understand the mechanism underlying metabolic inborn errors. Multidisciplinary teams would manage the disease from the point of view of diverse clinician experts so the correct diagnosis and treatment would be decided with precision(AU)

Introducción: El déficit de fumarasa es una enfermedad rara del metabolismo, autosómica, que cursa con hipotonía, hiperlactacidemia y convulsiones. El diagnóstico basado en pruebas de laboratorio debe realizarse con precaución ya que la mayoría de enfermedades relacionadas con el metabolismo presentan la misma sintomatología: hipotonía, convulsiones y acidemia láctica y pirúvica. Método: Analizar retrospectivamente el manejo farmacológico y nutricional de un neonato con síntomas relacionados con errores del metabolismo congénitos.Resultados:La paciente de 3 meses de vida presentaba una mutación heterocigota en el gen de la fumarasa y síntomas relacionados con la alteración de la función enzima. La paciente presentaba hiperlactacidemia, aciduria orgánica y alteraciones analíticas de los aminoácidos. El primer diagnóstico supuesto fue un déficit de piruvato deshidrogenasa, por lo que se inició tratamiento nutricional con dieta cetogénica. Tras el alta de la paciente, volvió a ingresar por urgencias sufriendo una parada cardíaca y descompensación metabólica. El test genético reveló la presencia de una mutación heterocigota en el gen de la fumarasa. La sintomatología clínica pudo haber empeorado debido al difícil diagnóstico. Conclusiones: El tratamiento farmacológico y nutricional del déficit de fumarasa es esencial para la buena evolución del paciente, pero es necesario que se realicen más estudios para entender con profundidad el mecanismo de los errores congénitos del metabolismo Los equipos multidisciplinares permiten manejar la enfermedad desde distintos puntos de vista clínicos para un diagnóstico correcto y poder decidir el tratamiento adecuado con precisión(AU)

Evaluation of quality indicators for nutrition and metabolism in critically ill patients: role of the pharmacist.

OBJECTIVE: To assess compliance in a Spanish intensive care unit (ICU) with 8 of the 13 quality indicators of the Spanish Society of Intensive Medicine and Coronary Units (Sociedad Española de Medicina Intensiva y Unidades Coronarias, SEMICyUC) related to nutrition and metabolism in critically ill patients. PATIENTS AND METHODS: The study included all patients over 18 years of age with an ICU stay of >48 hours between January and May 2019. The pharmacist was integrated into the daily activity of the multidisciplinary team of a 20-bed ICU to monitor and carry out the control of the quality indicators of the SEMICyUC. Studied indicators refer to: nutritional risk assessment and nutritional status (three indicators), glycaemic control, calculation of calorie-protein requirements, and use of early enteral nutrition or adequate parenteral nutrition. Compliance with each indicator was measured as the percentage of patients. RESULTS: 110 patients were included and 73 (66.4%) were male. Compliance results were: blood glucose range (90.7%), severe hypoglycaemia (0%), identification of patients at nutritional risk (58.2%) or with possible refeeding syndrome (8.9%), assessment of nutritional status at admission (58.2%), calculation of calorie-protein requirements (77.8%), early enteral nutrition (96.4%), and adequate use of parenteral nutrition (37.8%) CONCLUSION: Compliance with indicators related to glycaemic control and artificial nutrition (enteral and parenteral nutrition) was higher than reference standards, but there is a need to improve compliance with indicators related to nutritional risk and status at ICU admission. The hospital pharmacist integrated into the ICU multidisciplinary team can add value to the nutrition monitoring and quality indicators of the nutritional process of the critical patient, providing safe and effective nutritional therapy to patients.

Cerebral toxoplasmosis associated with treatment with rituximab, azathioprine and prednisone for dermatomyositis.

We observed a severe case of cerebral toxoplasmosis in a 22-year-old woman diagnosed with dermatomyositis in 2016 in Venezuela, and treated with rituximab and azathioprine. The patient met clinical and microbiological criteria. Treatment with pyrimethamine and sulfadiazine was initiated, and the patient was discharged. She was rehospitalized with signs and symptoms of a manic episode. During hospitalization, the patient developed acute kidney injury related to sulfadiazine crystalluria. Finally, acute kidney injury was resolved and the patient was successfully discharged.

Morbidity Outcomes of Very Low Birth Weight Neonates Receiving Parenteral Nutrition with Fish Oil Enriched Lipid Emulsion or Lipid Emulsion with Soybean Oil: An Observational Study.

Intralipid (Fresenius Kabi) was the most commonly used lipid emulsion in parenteral nutrition (PN), with a 100% soybean oil composition, a low vitamin E content, and a ω-6: ω-3 ratio of 7:1. A recent alternative formulation is SMOFlipid (Fresenius Kabi), with a ω-6: ω-3 ratio of 5:2 and higher vitamin E content. A retrospective observational study was conducted to determine neonatal morbidity in very low birth weight (VLBW) premature infants during two periods: P1, when PN was based exclusively on Intralipid, and P2, when only SMOFlipid was supplied. In total, 170 VLBW neonates were analyzed, of whom 103 received PN for more than 6 days, 56 during P1, and 47 during P2. In both periods, the antenatal and neonatal characteristics of the cohort were comparable. In this analysis, the prevalence of associated comorbidities was determined. During P2, there were fewer cases of moderate to severe bronchopulmonary dysplasia (BPD) and of cholestasis, but more cases of late sepsis, mainly Staphylococcus epidermidis. No changes in the prevalence of other neonatal comorbidities were observed. We believe that the SMOFlipid used in PN could discreetly improve the prevalence of cholestasis or BPD.

Vaccination in patients under monoclonal antibody treatment: an updated comprehensive review.

INTRODUCTION: Monoclonal antibodies (mAbs) have become an increasing source of biological treatments. Clinicians should make an effort to update their knowledge on mechanisms of action, indications, and adverse events of these novel therapies. Most of them have immunosuppressive effects and, therefore, vaccination is indicated. AREAS COVERED: vaccination of patients under mAbs therapies. EXPERT OPINION: Recommendations on vaccination are still based on expert recommendations and have not been updated in recent years. Specific recommendations for each mAb have not been addressed in the current literature. The aim of this comprehensive review was to collect all the therapeutic mAbs approved up to 1 January 2020 and, based on previous recommendations and the pharmaceutical characteristics of each drug, to propose an updated guide with recommendations on vaccination. Influenza, sequential pneumococcal and Hepatitis B vaccination in patients with negative serology were the only consistent recommendations. Hepatitis A vaccination was proposed for mAbs with special hepatotoxic characteristics. Other vaccines are reviewed and discussed. Several non-immunosuppressive mAbs were detected and, therefore, vaccinations not recommended. We hope that this review can serve as a starting point for compiling updated vaccination recommendations and collecting all the therapeutic mAbs approved up to 2020.

Cutaneous leishmaniasis associated with TNF-α blockers: a case report.

Leishmaniasis is a chronic protozoan disease that is found in diverse geographical areas of the world. Leishmania spp. are endemic in the Mediterranean coasts of southern Europe. Tumour necrosis factor alpha (TNF-α) plays an important role in the defence of the host against infection by Leishmania spp. In this case report we describe Leishmania infection caused by a monoclonal antibody against TNF-α: infliximab. A 51-year-old patient with psoriatic arthritis treated with infliximab, 5 mg/kg every 6 weeks as immunomodulatory treatment and methotrexate 10 mg weekly as a conventional disease-modifying antirheumatic drug, visited his otorhinolaryngologist owing to a lesion in his left nostril. The lesion was diagnosed as cutaneous leishmaniasis so treatment with infliximab was suspended. The patient was then treated with liposomal amphotericin B and showed a total recovery of the lesion; liposomal amphotericin B was maintained at 5 mg/kg monthly.