Effectiveness and safety in the management of chronic inflammatory diseases with etanercept and infliximab biosimilars in Colombian patients

Objective: To determine the effectiveness and safety of infliximab and etanercept biosimilar drugs in patients diagnosed with rheumatoid arthritis, ankylosing spondylitis, ulcerative colitis, and psoriasis in a specialized institution in Colombia, between 2015 and 2019. Methods: A retrospective study in patients treated with infliximab and etanercept biosimilar drugs treated in an institution specializing in the management of rheumatological diseases, to verify the clinimetric indicators of effectiveness and reports of adverse drug reactions. Clinical, sociodemographic, and pharmacological variables were identified over 5 years of follow-up. Results: 207 patients were identified with a mean age of 48.7 ± 15.1 years, 61.4% were women. Of the patients, 58.0% (n = 120) used infliximab and 42.0% (n = 87) etanercept. It was found that 46 (22.2%) patients had adverse drug reactions. At the end of the observation period, 61.6% (n = 72) of the patients with RA had achieved control of the disease (mild activity or remission), and 57.9% (n = 117) had problems with access to and persistence with therapy. Conclusion: In a group of patients treated in Colombia, the biosimilars of infliximab and etanercept showed proportions of effectiveness and safety comparable to the reference drugs, but lack of adherence to treatment was quite common.

Objetivo: Determinar la efectividad y la seguridad de medicamentos biosimilares de infliximab y etanercept en pacientes con diagnóstico de artritis reumatoide, espondilitis anquilosante, colitis ulcerativa y psoriasis en una institución especializada de Colombia, entre los arios 2015 y 2019. Métodos: Estudio retrospectivo, en pacientes tratados con infliximab y etanercept biosimilares, atendidos en una institución especializada en el manejo de enfermedades reumatológicas, para verificar los indicadores clinimétricos de efectividad y reportes de reacciones adversas medicamentosas. Se identificaron variables clínicas, sociodemográficas y farmacológicas durante cinco años de seguimiento. Resultados: Se identificaron 207 pacientes, con una edad media de 48,7 ± 15,1 años, el 61,4% de los cuales eran mujeres. El 58% (n = 120) de los pacientes utilizó infliximab y el 42% (n = 87) etanercept. Se encontró que 46 (22,2%) pacientes presentaron reacciones adversas al medicamento. Al final del periodo de observación, un 61,6% (n = 72) de los pacientes con AR había alcanzado el control de la enfermedad (actividad leve o remisión) y, en general, el 57,9% (n = 117) tuvo problemas de acceso y persistencia a la terapia. Conclusión: En un grupo de pacientes tratados en Colombia, los biosimilares de infliximab y etanercept mostraron proporciones de efectividad y seguridad comparables a los medicamentos de referencia, pero fue bastante común la falta de adherencia al tratamiento.

Medicamentos biosimilares en Colombia: una revisión desde el consumo informado / Biosimilar Medicines in Colombia: An Approach from the Informed Consumption / Medicamentos biossimilares na Colômbia: uma revisão desde o consumo informado

Resumen Introducción: este artículo presenta un análisis sobre medicamentos biosimilares en Colombia con miras a establecer si existe un consumo informado respecto de estos fármacos, teniendo en cuenta la calidad y cantidad de información que circula en relación con su disponibilidad y acceso económico (precios). Desarrollo: el tipo de estudio es cualitativo con un diseño documental a partir de la revisión en bases de datos como Pubmed, Scopus, Scielo, Vlex y Redalyc, bases de información de registros sanitarios de agencias reguladoras de medicamentos (FDA, EMA e Invima) y el Sistema de Información de Vademecum Med Informática. Uno de los biosimilares autorizados en FDA y cuatro de la EMA se encuentran registrados en el Invima; sin embargo, son más los biosimilares no autorizados ni en FDA ni en EMA que se encuentran registrados en el Invima, los cuales aún no aparecen con esta clasificación de biosimilares ni en la agencia reguladora colombiana ni en ningún otro medio oficial o comercial. De los medicamentos biológicos de referencia de estos biosimilares, 12 tienen control de precios y 7 han sido autorizados al menos una vez vía judicial a los usuarios del sistema. Conclusiones: si bien, la reglamentación ha sido de gran avance en relación con el acceso a biosimilares y, en consecuencia, a sus biológicos pioneros, el sistema aún tiene barreras jurídicas, de información, disponibilidad y acceso que dificultan la protección y efectividad del derecho a la salud de la población en términos de un consumo informado de estos.

Abstract Introduction: This article presents an analysis of biosimilar drugs in Colombia, aiming at critically analyzing whether the consumption of biosimilar drugs in Colombia is fully informed or if it rather is characterized for its lack of information. Informed consumption in the sense of taking into account the quality and quantity of the information circulating in relation to the availability and affordability (prices) of biosimilar drugs. Development: This is a qualitative documentary analysis, based on the review of databases such as Pubmed, Scopus, Scielo, Vlex and Redalyc, and sanitary databases of drugs regulatory agencies (FDA, EMA and the Colombian Invima) and the Vademecum Med Informatica. One of the biosimilars authorized by FDA and four of those by EMA were also registered before by the Invima. However, the number of Invima authorized biosimilars is higher than that authorized by FDA and EMA. It is also important to highlight the fact that any biosimilar is not registered as such neither before the Invima nor before any other official or commercial source. Out of the biological reference products with biosimilars, twelve have regulated price and seven have been authorized at least once via court ruling. Conclusions: Although the regulations are progressive in relation to the access to biosimilars and, consequently, to their biological pioneers, the system still has legal, availability and information barriers that undermine the protection and effectiveness of the right to health.

Resumo Introdução: este artigo apresenta uma análise sobre medicamentos biossimilares na Colômbia com vista a estabelecer se existe um consumo informado respeito destes fármacos, tendo em conta a qualidade e quantidade de informação que circula em relação com a sua disponibilidade e acesso econômico (preços). Desenvolvimento: o tipo de estudo é qualitativo com um desenho documental a partir da revisão em bases de dados como Pubmed, Scopus, Scielo, Vlex e Redalyc, bases de informação de registros sanitários de agências reguladoras de medicamentos (FDA, EMA e Invima) e o Sistema de Informação de Vademecum Med Informática. Um dos biossimilares autorizados em FDA e 4 da EMA, se encontram registrados no Invima, no entanto são mais os biossimilares não autorizados nem na FDA nem na EMA que se encontram registrados no Invima, os quais ainda não aparecem com esta classificação de biossimilares nem na agência reguladora colombiana, nem em nenhum outro meio oficial ou comercial. Dos medicamentos biológicos de referência destes biossimilares, 12 têm controle de preços e 7 têm sido autorizados pelo menos uma vez via judicial aos usuários do sistema. Conclusões: se bem a regulamentação tem sido de grande avanço em relação com o acesso a biossimilares e, consequentemente, a seus biológicos pioneiros, o sistema ainda tem barreiras jurídicas, de informação, disponibilidade e acesso que dificultam a proteção e efetividade do direito à saúde da população em termos de um consumo informado dos mesmos.

Revisiting the Therapeutic Potential of Bothrops jararaca Venom: Screening for Novel Activities Using Connectivity Mapping.

Snake venoms are sources of molecules with proven and potential therapeutic applications. However, most activities assayed in venoms (or their components) are of hemorrhagic, hypotensive, edematogenic, neurotoxic or myotoxic natures. Thus, other relevant activities might remain unknown. Using functional genomics coupled to the connectivity map (C-map) approach, we undertook a wide range indirect search for biological activities within the venom of the South American pit viper Bothrops jararaca. For that effect, venom was incubated with human breast adenocarcinoma cell line (MCF7) followed by RNA extraction and gene expression analysis. A list of 90 differentially expressed genes was submitted to biosimilar drug discovery based on pattern recognition. Among the 100 highest-ranked positively correlated drugs, only the antihypertensive, antimicrobial (both antibiotic and antiparasitic), and antitumor classes had been previously reported for B. jararaca venom. The majority of drug classes identified were related to (1) antimicrobial activity; (2) treatment of neuropsychiatric illnesses (Parkinson's disease, schizophrenia, depression, and epilepsy); (3) treatment of cardiovascular diseases, and (4) anti-inflammatory action. The C-map results also indicated that B. jararaca venom may have components that target G-protein-coupled receptors (muscarinic, serotonergic, histaminergic, dopaminergic, GABA, and adrenergic) and ion channels. Although validation experiments are still necessary, the C-map correlation to drugs with activities previously linked to snake venoms supports the efficacy of this strategy as a broad-spectrum approach for biological activity screening, and rekindles the snake venom-based search for new therapeutic agents.

A phase III, randomized, non-inferiority study comparing the efficacy and safety of biosimilar filgrastim versus originator filgrastim for chemotherapy-induced neutropenia in breast cancer patients

OBJECTIVES: To compare the efficacy and safety of two filgrastim formulations for controlling chemotherapy-induced neutropenia and to evaluate the non-inferiority of the test drug relative to the originator. METHODS: This phase III non-inferiority study had a randomized, multicenter, and open-label design. The patients were randomized at a ratio of 1:1 with a follow-up period of 6 weeks for each patient. In both study arms, filgrastim was administered subcutaneously at a daily dose of 5 mg/kg body weight. The primary endpoint was the rate of grade 4 neutropenia in the first treatment cycle. The secondary endpoints were the duration of grade 4 neutropenia, the generation of anti-filgrastim antibodies, and the rates of adverse events, laboratory abnormalities, febrile neutropenia, and neutropenia of any grade. RESULTS: The primary efficacy analysis demonstrated the non-inferiority of the test drug compared with the originator drug; the upper limit of the 90% confidence interval (CI) for the rate of neutropenia between the two groups (12.61%) was lower than the established margin of non-inferiority. The two treatments were similar with respect to the secondary endpoints and safety. CONCLUSION: The efficacy and safety profile of the test drug were similar to those of the originator product based on the rate of grade 4 neutropenia in the first treatment cycle. This study supports Anvisa’s approval of the first biosimilar drug manufactured by the Brazilian industry (Fiprima¯).