Medicamentos bioterapéuticos: uso de toxinas botulínicas en la era de biosimilares

Introducción: Las toxinas botulínicas son medicamentos bioterapéuticos con grandes aplicaciones en el campo de la neurología, como la cefalea y los movimientos anormales. Debido a la importancia médica y al incremento de las indicaciones terapéuticas de la toxina botulínica, este artículo pretende hacer claridad acerca de la terminología básica con respecto a la naturaleza de este medicamento, a las diferencias estructurales con medicamentos convencionales y aspectos importantes en relación con su potencia biológica e inmunogenicidad, para así comprender las potenciales diferencias entre las toxinas disponibles y conceptuar en torno a la no intercambiabilidad o sustitución de una toxina por otra. Materiales y métodos: Revisión no sistemática, según lo recomendado en la Escala para la Verificación de los Artículos Revisiones Narrativas (Sanra). Conclusiones: Los medicamentos biológicos no son intercambiables entre sí, aunque demuestren bioequivalencia. No se pueden evaluar como medicamentos genéricos intercambiables porque son biológicos; no existen estudios comparativos cabeza a cabeza; son diferentes, debido al proceso individual de manufactura.

Introduction: Botulinum toxins are biotherapeutic drugs with great applications in the field of neurology such as headache and abnormal movements. Due to the medical importance and the increase in therapeutic indications of botulinum toxin, this article aims to clarify the basic terminology regarding the nature of this drug, the structural differences with conventional drugs and important aspects in relation to its biological potency and immunogenicity in order to understand the potential differences between the available toxins and conceptualize regarding the non-interchangeability or substitution of one toxin for another. Materials and methods: Non-systematic review as recommended in the Scale for the Verification of Narrative Review Articles (SANRA). Conclusions: Biological drugs are not interchangeable with each other, even if they demonstrate bioequi-valence. They cannot be evaluated as interchangeable generic drugs because they are biologics. There are no head-to-head comparative studies. They are different due to the individual manufacturing process.

Efficacy and safety analysis of intravitreal bio-similar products of bevacizumab in patients with macular edema because of retinal diseases

Purpose: The purpose of this study was to evaluate retrospectively the efficacy and safety profile of intravitreal injection of bevacizumab bio?similar product Zybev(Z) for macular edema because of retinal diseases. Methods: A retrospective analysis was conducted on patients with macular edema because of retinal diseases, who had been administered intravitreal injections of bio?similar bevacizumab at a tertiary eye care center. Changes in the retinal thickness and visual acuity were evaluated to judge the efficacy, and adverse events were noted for the safety profile over a period of 6 weeks. Results: A total of 104 patients were included in the study. The mean age of the patients was 53 ± 13.5 years. The mean pre?injection best corrected visual acuity (BCVA) was 1.32 ± 0.70 log minimum angle of resolution (logMAR) with a central subfield thickness (CST) of 429.26 ± 204.30 ?m, and the post?injection BCVA at 6 weeks was 1.13 ± 0.71 logMAR with a CST of 302.26 ± 104.50 ?m; this change was statistically significant (P < 0.05) for all groups. The mean average cube thickness (?m) decreased from 11.85 ± 1.96 pre?injection to 10.52 ± 1.75 post?injection, and the mean average cube volume (mm3) decreased from 329.30 ± 54.35 to 302.23 ± 49.56 (P < 0.05). During the follow?up period after injection, no patient had inflammation, endophthalmitis, an increase in intra?ocular pressure, or systemic side effects. Conclusion: This short?term retrospective analysis provides evidence regarding the efficacy and safety of intravitreal injection of bio?similar products of bevacizumab for the treatment of macular edema because of retinal diseases

Efficacy and safety of biosimilar romiplostim in Indian patients with chronic immune thrombocytopenia: A multicentric retrospective study

Context and Aims: To evaluate the efficacy and safety of biosimilar romiplostim in Indian patients with immune thrombocytopenic purpura (ITP). Settings and Design: Multicentre, retrospective observational study. Methods and Material: Patients with chronic ITP who received biosimilar romiplostim from July 2019 to March 2020 across 3 major hospitals in Guwahati, India, were included. The study outcomes were the platelet response (platelet count > 50 × 109/L), time to first response, number of dose-limiting events, and the median effective dose. Statistical Analysis Used: Descriptive. Results: Of 32 patients included in this analysis, majority (59.4%) were females. The mean (SD) age was 40.37 (15.79) years, and mean age at ITP diagnosis was 38.53 years. The median number of romiplostim doses were 27.5 (range: 10-42) over a period of 10 months; median romiplostim dose used was 4.2 ?g/kg (range: 2.8-5 ?g/kg). Platelet response was achieved as early as after one week in 9 (28.12%) patients, which continued to increase to 24 (75%) patients after the second, 30 (93.75%) patients after the third and all 32 (100%) patients after four weeks of romiplostim administration. The median platelet count was 161 × 109/L. Dose reduction was done in a total of 21 patients. Thrombocytosis (46.88%), elevated liver enzymes (15.63%) and myalgia (15.63%) were the most common adverse events. Conclusions: Biosimilar romiplostim was effective in achieving and maintaining platelet response without any new safety concerns in Indian adult patients with chronic ITP. The median effective dose of romiplostim required in our patients was lower as compared with the standard prescribed dose.

Efficacy of a biosimilar ranibizumab monotherapy for the treatment of retinopathy of prematurity

Purpose: To evaluate the efficacy of a biosimilar ranibizumab (Razumab) on outcomes of retinopathy of prematurity (ROP) for the first time. Methods: This retrospective study included infants presenting with stage 3+ ROP either in zone 1 or zone 2 posterior or aggressive posterior ROP (APROP). All eligible infants received intravitreal razumab (0.25 mg/0.025 ml) monotherapy. Follow?up was continued monthly till complete retinal vascularization was achieved while retreatment with razumab was given when recurrent neovascularization was noted. In case of no recurrence but incomplete vascularization, laser photocoagulation was done to the residual avascular retina. Results: We included 118 eyes of 59 infants with a median gestational age of 30 weeks and median birth weight of 1250 grams. At presentation, APROP was found in 28 eyes (24%) of 14 babies while stage 3 disease was seen in zone 1 in another 28 eyes (24%) and the remaining 62 eyes (52%) had stage 3 ROP in zone 2 posterior region. Complete resolution of ROP along with complete vascularization was seen in 22 eyes (19%) at a median of 55 days (IQR = 31–56 days) and 42 eyes (35%) showed a recurrent neovascularization at a median of 51 days post razumab (IQR = 42– 55 days). The cumulative incidence of recurrence of neovascularization (21%, 95% CI = 14%–29%) peaked at seven weeks and was significantly higher in eyes with APROP (43%, 95% CI = 27%–63%) compared to eyes without APROP (13.4%, 95%CI, 8%?22%) (P < 0.001). Conclusion: Razumab appears to be safe and effective in treating ROP, with about a third requiring reinjection at seven weeks after the first dose.

Conception of National Biologics Registry for Pediatric Rheumatology: Need of the Hour and the Way Forward

The outcome for children with rheumatic diseases has been dramatically altered by the use of biological therapies. Increasing use of these agents will need careful monitoring for long term safety, particularly in children. Current data on safety of these drugs stem exclusively from Western literature. There is clear need for a registry of all children with rheumatic diseases who are commenced on biological agents to ensure appropriate pharmacovigilance. In this perspective, we discuss the need for and the role of a biologics registry for children with rheumatic diseases in India.

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.

Real-world use and acceptance of biosimilar rituximabin oncology practice in India

Background: To describe the treatment patterns, patient characteristics and usage pattern of biosimilar rituximab for the treatment of Non-Hodgkin lymphomas (NHL) in India.Methods:This real-world, retrospective, analysis included adult patients receiving biosimilar rituximabbetween April 2021 and March 2022. Results:A total of 750 patients with NHL who received biosimilar rituximab were included. The most common indications reported in this analysis were diffuse large cell B-cell lymphoma [DLBCL, 64.5% (n=484)], follicular lymphoma, [FL, 23.7% (n=178)], and mantle cell lymphoma [MCL, 5.3% (n=40)]; other subtypes constituted 6.4% of the patients (n=48). The mean age of patients among DLBCL, FL and MCL was 65.5, 55.3 and 57 years, respectively. Across the lymphomas, >90% of the patients received R-chemo as first-line therapy. R-CHOP was the most common regimen across indications. Conclusions:Biosimilar rituximab-based chemotherapyis being adopted in real-world clinical practice in India for the management of patients with B-cell NHL including DLBCL, FL, MCL and other lymphomas.

A prospective, randomized, parallel group, double blind, multicenter study to compare the efficacy, safety and immunogenicity of Lupin’s Ranibizumab with Lucentis® in patients with neovascular age-related macular degeneration

Purpose: The present study compares the efficacy, safety, and immunogenicity of Lupin’s biosimilar ranibizumab with that of Lucentis® in patients with neovascular age-related macular degeneration. Methods: This prospective, double-blind, multi-centric phase-III study was conducted across 19 centers in India. A total of 202 patients with neovascular age-related macular degeneration were randomized (1:1) to receive either Lupin’s biosimilar ranibizumab or Lucentis®, 0.5 mg, as an intravitreous injection once every month for 3 months. The primary efficacy endpoint was the proportion of patients who lost fewer than 15 letters from baseline in best-corrected visual acuity. The safety profile included assessment of adverse events, ophthalmic examination, physical and systemic examination, and vital parameters. The immunogenicity assessment was based on evaluation of anti-drug antibodies. Results: Overall, 174 patients (87 [86.14%] in each group) completed the study. The demographics and baseline characteristics were comparable between the treatment groups. The proportion of patients losing fewer than 15 letters from baseline best corrected visual acuity score in the study eye was comparable between two groups. The difference between Lupin’s ranibizumab and Lucentis® for the proportion of patients who lost fewer than 15 letters was within the predefined equivalence margin (intention-to-treat population: 1.0%; 95% confidence interval [CI], ?3.3% to 5.4% and per protocol population: 1.2%; 95% CI, ?3.2% to 6.4%). The incidence of treatment-emergent adverse events was comparable, and 11 (10.89%) patients in Lupin’s ranibizumab and 19 (18.81%) patients in Lucentis® group had at least one treatment-emergent adverse event. The immunogenicity incidence as assessed by proportion of patients with positive anti-drug antibodies was numerically lower in Lupin’s ranibizumab (4.95%) than Lucentis® (12.87%). Conclusion: Lupin’s biosimilar ranibizumab demonstrated therapeutic equivalence, desirable safety, and favorable immunogenicity profile compared to Lucentis

Linfomas no Hodgkin indolentes y terapia anti-CD20: una revisión de la literatura / Indolent non-Hodgkin's lymphomas and anti-CD20 therapy: a literature review

Introducción: Los linfomas no Hodgkin indolentes se destacan por el reto que suponen desde el punto de vista terapéutico. La introducción de la terapia con rituximab, un anticuerpo monoclonal que se une al antígeno CD20 de la membrana de los linfocitos B, revolucionó los tratamientos hasta ese momento y abrió el camino para el desarrollo de otros anticuerpos monoclonales anti-CD20. Objetivo: Describir las características generales de los linfomas no Hodgkin indolentes y de los anticuerpos monoclonales anti-CD20, así como el rol de la terapia anti-CD20 en dichas enfermedades. Métodos: Se realizó una revisión de la literatura publicada en los últimos 20 años, disponible en los repositorios: Scielo, Scopus, Pubmed/Medline, ScienceDirect y Mediagraphic. Se emplearon para elaborar este manuscrito 35 documentos, de ellos 80 por ciento correspondieron a los últimos 5 años. Conclusiones: La sólida evidencia científica, acumulada durante las últimas dos décadas, respalda el uso clínico de los anticuerpos monoclonales anti-CD20 en el tratamiento de los linfomas no Hodgkin indolentes. El uso efectivo de estos fármacos como agentes únicos o combinados con quimioterapia demuestran su versatilidad terapéutica(AU)

Introduction: Indolent non-Hodgkin's lymphomas are notable for the challenge they pose from a therapeutic point of view. The introduction of rituximab, a monoclonal antibody that binds to the CD20 antigen of the B-lymphocyte membrane, revolutionized treatments up to that time and opened the way for the development of other anti-CD20 monoclonal antibodies. Objective: To describe the general characteristics of indolent non-Hodgkin's lymphomas and anti-CD20 monoclonal antibodies, as well as the role of anti-CD20 therapy in these diseases. Methods: A review of the literature published in the last 20 years, available in the repositories: Scielo, Scopus, Pubmed/Medline, Science Direct and Mediagraphic, was performed. Thirty-five papers were used to prepare this manuscript, 80 percent of which corresponded to the last 5 years. Conclusions: Strong scientific evidence, accumulated over the last two decades, supports the clinical use of anti-CD20 monoclonal antibodies in the treatment of indolent non-Hodgkin's lymphomas. The effective use of these drugs as single agents or in combination with chemotherapy demonstrates their therapeutic versatility(AU)

In vitro functional similarity assessment of a proposed biosimilar BAT1706 to bevacizumab / 药学学报

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.

Taxas de descontinuação do tratamento após a troca de um biológico originador por um biossimilar em pacientes com doenças inflamatórias intestinais: revisão sistemática e metanálise / Discontinuation rates following a switch from a reference to a biosimilar biologic in patients with inflammatory bowel disease: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Biologics have revolutionized the treatment of inflammatory bowel disease (IBD). However, these drugs had a significant influence on treatment-related costs, which resulted in the development of biosimilars. OBJECTIVE: This systematic review and meta-analysis aimed to evaluate the drug discontinuation rate in the IBD population who switched from originator to biosimilars in real-world switching studies and address potential nocebo effects as reasons for drug discontinuation. METHODS: Medline (via PubMed), EMBASE, Cochrane Library, and abstract databases of selected congresses were screened for reports of monoclonal antibody (mAb) switching with a minimum post-switch follow-up of >6 months or three infusions. All available information on discontinuation rates was assessed. RESULTS: A total of 30 observational studies were included, involving 3,594 patients with IBD. Twenty-six studies reported a switch from infliximab to CT-P13, two studies involved a switch to SB2, and switching information was not available in two studies. The discontinuation rates were 8%, 14%, and 21% at 6, 12, and 24 months, respectively. The main reasons for drug discontinuation and their respective risks were: disease worsening (2%), remission (4%), loss of adherence (4%), adverse events (5%), and loss of response (7%). The quality of the evidence ranged from low to very low depending on the outcome analyzed. Subjective symptoms leading to drug discontinuation were infrequently reported, and the nocebo effect was clearly assessed in just one of the included papers. CONCLUSION: Discontinuation rates following a switch to a biosimilar in patients with IBD increase over time. However, it was not possible to confirm the nocebo effect as a reason for discontinuation. Therefore, long-term studies evaluating the use of biosimilars to monitor adverse events and potential nocebo effects in post-marketing surveillance are still needed.

RESUMO CONTEXTO: Os biológicos revolucionaram o tratamento da doença inflamatória intestinal (DII). Ademais, esses medicamentos influenciaram os custos relacionados ao tratamento. Tal aumento significativo nos gastos com o tratamento motivou desenvolvimento dos biossimilares. OBJETIVO: Esta revisão sistemática e metanálise objetivou avaliar a taxa de descontinuação de medicamentos na população com DII que foi submetida à troca do biológico originador para um biossimilar, em estudos observacionais que abordaram possíveis razões para a descontinuação do tratamento. MÉTODOS: Tendo como base de dados Medline (via PubMed), EMBASE, Cochrane Library e resumos de congressos médicos, foram rastreados artigos com relatos de troca de um biológico originador por um biossimilar, com acompanhamento pós-troca de no mínimo 6 meses ou três infusões. Todas as informações disponíveis sobre as taxas de descontinuação foram avaliadas. RESULTADOS: Foram incluídos no total 30 estudos observacionais, envolvendo 3.594 pacientes com DII. Vinte e seis estudos relataram uma mudança do infliximabe para CT-P13, dois estudos envolveram uma mudança para o SB2, e as informações sobre a troca não estavam disponíveis em dois estudos. As taxas de descontinuação foram de 8%, 14% e 21% aos 6, 12 e 24 meses, respectivamente. Os principais motivos para a descontinuação do medicamento e seus respectivos riscos foram: agravamento da doença (2%), remissão (4%), perda de adesão (4%), eventos adversos (5%) e perda de resposta (7%). A qualidade da evidência variou de baixa a muito baixa, dependendo do resultado analisado. Os sintomas subjetivos que levaram à descontinuação do medicamento foram relatados com pouca frequência, e o efeito nocebo foi claramente avaliado em apenas um dos artigos incluídos. CONCLUSÃO: As taxas de descontinuação após a mudança para um biossimilar em pacientes com DII aumentam com o tempo. No entanto, não foi possível confirmar o efeito nocebo como motivo da descontinuação. Portanto, ainda são necessários estudos em longo prazo avaliando o uso de biossimilares para monitorar eventos adversos e potenciais efeitos nocebo na vigilância pós-comercialização.

The Modern Engineering In Biosimiliar Drugs Development As Bioactive Gene Clonning

Bio therapeutic product tends to similar properties like- efficacy, Safety and qualityto a licensed bio- originator. USFDA guideline clearly said that Bio-Similar drugs are not genericmedications nor identical to the innovator medicine and also it’s not ensuring therapeuticequivalence with innovator drug. Getting Bio-Similar product marketing approval is achallenging task. To improve access of Bio-Similar drugs within the US market, US-FDA allowsabbreviated pathway for their approval. Recently India is becoming a most preferabledestination for Bio-Similar manufacturers, because of Make in India program. Introduction ofrecombinant technique to prepare Monoclonal antibody based Bio-Similar drug becomingpopular within pharmaceutical manufactures because of many recent patent expiries ofBiologics. The biologies are produced by cell culture method; hence, chances of variability’s aremore as comparable with the chemically synthesized conventional medicine and variousbiological medicines has led to developed Bio-Similar drugs across the globe. The biologies areproduced by cell culture method; hence, chances of variability’s are more as comparable withthe chemically synthesized conventional medicine. Therefor it is impossible to produce anidentical copy of an innovator product; hence, Bio-Similar is not considered as generic drugs.These drugs are Twin but not a clone of the innovator drug. The Bio-Similar drugs always facechallenges regarding verification of the similarity, the interchange ability, unique naming todifferentiate the various Bio-Pharmaceutical products, commercial opportunities, IPR andpublic safety.

Immunopharmacology 2020. V International Congress on Immunopharmacology

The Organizing Committee of the V International Congress on Immunopharmacology (Immunopharmacology 2020) organized by the Cuban Society of Pharmacology, BioCubaFarma and the International Union of Basic and Clinical Pharmacology (IUPHAR) would like to invite you to participate in this important event, scheduled for June 9 to 13, 2020 at the Convention Centre of the Melia Marina Varadero Hotel, Varadero Beach, Matanzas, Cuba. The Congress will be formed by different workshops and symposia such as: Fifth workshop on new advances in immunopharmacology Fifth workshop on neuroimmunology, neuroimmunopharmacology and neuroimmunomodulation. Immunopharmacology of brain tumors Symposium on hereditary ataxias Fifth symposium on pharmacology of cytochrome P450 and transporters Fourth symposium on inflammation and pain 2nd symposium on NFkB Synthetic peptides as immunopharmacological tools Novel designs in clinical trials. Biosimilar pharmaceuticals Pharmacogenetics, pharmacogenomics, proteomics and phosphoproteomics Immune response in cancer First symposium on business and international cooperation on biologics Immunopharmacology 2020 is sponsored by: Cuban Society of Pharmacology (SCF) International Union of Basic and Clinical Pharmacology (IUPHAR) Latin-American Association of Pharmacology (ALF) PAHO / WHO BioCubaFarma National research centers: Finlay Vaccine Institute (IFV); Center of Genetic Engineering and Biotechnology (CIGB); Center of Molecular Immunology (CIM); Center for Control of Drugs, Equipment and Medical Devices (CECMED); National Center for Animal and Plant Health (CENSA); Tropical Medicine Institute "Pedro Kourí" (IPK); National Center for Biopreparations (BioCEN); Center for Drug Research and Development (CIDEM); Center for Clinical Trials (CENCEC); among others International Manufacturers and Companies The key objectives of the Congress are: To provide a progressive state-of-the-art report for scientists, manufacturers, governmental authorities and healthcare workers, who need to be updated about the latest scientific developments for human vaccines, including basic science, product development, market introduction, immunization programs and epidemiological surveillance. To promote the scientific collaboration among experts and institutions through the experience exchange, the presentation of results and the discussion on the conference topics. To accelerate progress in the development of vaccines and the acceptance and introduction of new methods and technologies. Opening lectures, oral presentations and posters will provide you the opportunity to be involved in a high quality congress to discuss about the progress in the field of immunology and pharmacology sciences(AU)

Multi-dimensional Focus on the Management and Clinical Use of Biosimilar Products / 中国药房

OBJECTIVE：To provide reference for summarize the management and clinical use levels of biosimilar products . METHODS：Related policies and regulations about approval and application of biosimilar products were retrieved from domestic and foreign supervision departments and WHO. The biosimilar products were described from multi-dimensional aspects of whole life cycle of drugs ，generic name and prescription ，indication extrapolation ，clinical drug exchange ，pharmacovigilance，medical insurance payment system ，education and training. RESULTS & CONCLUSIONS ：Biosimilar products refer to therapeutic biological products which are similar to the reference drugs which have been approved for marketing in terms of quality ，safety and effectiveness. In R&D ，production，circulation，use and supervision links，the management of biosimilar products has its own characteristics in different countries/areas/organization. In the R&D stage ，biosimilar products do not need to independently verify their safety and effectiveness ，but only step by step use analytical methods to gradually clarify their high similarity with reference drugs in terms of structure and function. The name of biosimilar products in China is the same as that of the original drugs ，and the general name was used in prescription. For FDA to approve the indication extrapolation of biosimilar products ，it needs to be based on the data and information at the time of application ，the safety and effectiveness information of reference drugs ，and the consideration of relevant scientific elements of indications. It needs to be evaluated and used conditionally under supervision. The standard of FDA approval is strict，that is to say ，the approval standard of realizing interchangeability is higher than that of biological similarity which has no such concept in China. The enterprise community ，regulatory agencies ，academic institutions and hospital drug rooms need to communicate and exchange ，and further strengthen post market risk control and safety monitoring. China’s medical insurance department should establish an appropriate payment system and encourage the use of biosimilar products through the payment system. Meclical workers should learn the characteristics of biosimilar products so that they can make good use of biosimilar products in practice on the basis of understanding their technical evaluation.

Conceptos fundamentales de bioequivalencia y biosimilitud en la normativa chilena y controversias sobre intercambiabilidad / Chilean legislation on bioequivalence and biosimilarity and current controversies related to drug interchangeability

Los medicamentos constituyen un bien económico que forma parte del gasto público y privado y de la toma de decisiones en salud. El aseguramiento de su calidad, eficacia y seguridad resulta fundamental. Sin embargo, la variada oferta disponible en el mercado chileno, donde se reconocen productos innovadores y genéricos, constituye un escenario confuso para consumidores y proveedores en salud. En esta revisión pretendemos aclarar los conceptos de fármacos bioequivalentes (aplicable a compuestos de tamaño molecular pequeño) y fármacos biosimilares (para compuestos biológicos de mayor complejidad molecular). En ambos casos, el comportamiento en el organismo del principio activo debe ser demostrado mediante estudios realizados para este fin. Una aplicación directa del concepto de bioequivalencia es la intercambiabilidad, definida como la posibilidad de utilizar un producto de un mismo principio activo, mientras la forma farmacéutica y esquema de dosificación sean iguales. Las normas relativas a esta materia y los organismos públicos encargados, no solo debieran garantizar la seguridad y la eficacia en el intercambio entre productos, sino también aspectos relacionados con el costo, la accesibilidad a los fármacos y la implementación de una guía de homogeneización de conceptos y criterios de intercambiabilidad basados en la evidencia, lo cual impactaría en una mejor educación para los usuarios, reduciendo la asimetría de información entre el usuario y la industria. La importancia de la intercambiabilidad destaca en Chile en el contexto del Plan de Garantías Explícitas en Salud (GES) y la Ley de Protección Financiera para Diagnósticos y Tratamientos de Alto Costo en Salud (Ley Ricarte Soto). Sin embargo, no es posible garantizar que todos los productos alternativos al innovador presentes en el mercado chileno son bioequivalentes. El conocimiento disponible en esta temática puede impactar y contribuir a la toma de decisiones en los prescriptores y usuarios, así como en la elaboración de políticas públicas en torno a los productos farmacéuticos bioequivalentes y biosimilares en nuestro país.

Medicines are an economic good and a fundamental component of public and private health spending and decision-making. Assurance of their quality, efficiency, and safety is essential. In Chile, the wide variety of available drugs, including innovator products, and generics­some of which are certified as bioequivalent, while others are not­creates a potentially confusing scenario for both consumers and health providers. In this review, we intend to shed light on the concepts of bioequivalency (the standard permitting interchangeability for small-molecule drugs) and biosimilarity (the standard permitting interchangeability for biological compounds of greater molecular complexity). In both cases, how the active substance interacts with the host organism must be demonstrated by studies designed and carried out for this purpose. Interchangeability is defined as the possibility of using a product of the same active principle, as long as the pharmaceutical form and dosage scheme are the same. Regulations related to bioequivalence and biosimilarity must not only guarantee safety and efficacy when products are interchanged but also facilitate cost savings and access to medicines. Implementation of evidence-based guidelines that standardize concepts of interchangeability could lead to more educated usage and reduced information asymmetry between patients (users) and industry. Drug interchangeability is particularly relevant in two government health initiatives in Chile: the Explicit Guarantees in Health Care (GES) plan, and the Law on Financial Protection for High-Cost Diagnostics and Treatment in Health Care (also known as the "Ricarte Soto Law"). Nonetheless, it is not possible to guarantee that all alternative drug products on the Chilean market are bioequivalents of the reference product. Synthesis of the available knowledge on bioequivalent and biosimilar pharmaceutical products in Chile could facilitate and contribute to stakeholder decision-making and the development of better health policies.

Terapias biológicas del cáncer: un enfoque a favor de la accesibilidad / Biological cancer therapies: an approach towards accessibility

RESUMEN Los anticuerpos monoclonales son una poderosa herramienta para el diagnóstico de laboratorio y un instrumento cada vez más utilizado en el tratamiento de diversas enfermedades, siendo uno de los grupos más importantes de drogas en el tratamiento del cáncer. La revolución en el mundo de los anticuerpos ocurre en 1975 cuando Milstein y Köhler desarrollan la técnica de las hibridomas en Cambridge. Objetivo Hacer una revisión del uso de anticuerpos monoclonales en medicina y, en particular, en el tratamiento del cáncer. Se busca aportar una visión generalizada del concepto de anticuerpo monoclonal para explicar su aplicabilidad terapéutica y abordar un enfoque económico y sociosanitario de la obtención y acceso a las nuevas terapias. Método En la caracterización del fenómeno de investigación se empleó el estudio descriptivo, de recolección de datos documental y la correlación entre las distintas fuentes. Discusión Son aún elevados los costos tanto para el paciente como para los sistemas de salud pública, y se ha de optimizar la valoración costo-efectividad de modo que la rentabilidad y el acceso a tiempo para los pacientes puedan ser compatibles. Se deja abierto el reto del desarrollo de nuevos mAbs dirigidos a nuevas dianas, mejorar el perfil de seguridad, evitando o reduciendo las reacciones adversas inmunes y conseguir el abaratamiento del coste de producción mediante mejoras en la biotecnología.(AU)

ABSTRACT Monoclonal antibodies are a useful tool for laboratory diagnosis and an instrument used in the treatment of various diseases and represent one of the most important groups of new drugs for the treatment of cancer. The revolution in the world occured in 1975 when Milstein and Köhler discovered monoclonal antibodies in Cambridge. Objective To review the use of monoclonal antibodies in medicine and in the treatment of cancer. To provide a generalized vision of the concept of monoclonal antibody to explain its therapeutic applicability, and to approach an economic, health-care approach to obtaining and accessing new therapies. Method In the characterization of the research phenomenon, the descriptive study, the collection of documentary data and the correlation between the different sources were used. Discussion However, the costs for both the patient and the public health systems are still high, and the cost-effectiveness assessment must be optimized so that cost-effectiveness and access to time for patients can be compatible. And the challenge of developing new mAbs aimed at new targets, improving the safety profile, avoiding, or reducing adverse immune reactions and achieving lower production costs through improvements in biotechnology, is left open.(AU)

Análise clínica e econômica de "mundo real" da substituição do medicamento Remicade® (infliximabe referência) por Remsima™ (infliximabe biossimilar) em pacientes com artrite reumatoide, espondilite anquilosante e artrite psoriática / Clinical and economic "real world" analysis of the switching from Remicade® (infliximabe reference) by Remsima™ (infliximab biossimilar) in patients with rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis

Objetivo: O Planserv oferece cobertura à terapia biológica para as patologias de artrite reumatoide (AR), espondilite anquilosante (EA) e artrite psoriática (AP). Em agosto de 2016, 78 pacientes estavam em uso do medicamento Remicade® (infliximabe). Nessa data, o valor do Remicade® foi reduzido para o mesmo valor do Remsima™ (infliximabe biossimilar). Com isso, todos pacientes que estavam usando o Remicade® trocaram por Remsima™. Conduzimos um estudo para medir a descontinuidade da terapia e a economia. Métodos: Estudo de mundo real (coorte prospectiva), não controlado, em pacientes com AR, AP e EA que estavam utilizando Remicade® e trocaram para Remsima™, entre setembro de 2016 e setembro de 2017. O desfecho primário foi o índice de descontinuidade do tratamento (por qualquer causa). O desfecho secundário foi a taxa de "aumento da atividade da doença", medida por meio dos escores SDAI, BASDAI e CASPAR. Foi considerado como "aumento da atividade da doença" qualquer medida superior à medida inicial e que estivesse acima do limite de remissão da doença. Os valores de referência para "aumento da atividade da doença" foram as medidas históricas. O impacto econômico foi medido por uma análise de custo-minimização. Resultados: Em setembro de 2017, 5 (6%) pacientes que realizaram a troca do Remicade® para o Remsima™, descontinuaram a terapia (4 por falhas e 1 perda de acompanhamento). A taxa de descontinuação de referência (Remicade®) foi de 11% (9% de falha e 2% por perda de acompanhamento). As análises de subgrupo (descontinuidade da terapia por tipo de patologia) foram equivalentes. A taxa de "aumento da atividade da doença" ocorreu em 42% dos pacientes para o Remsima™ e em 46% para o Remicade®. As análises de subgrupo (por tipo de patologia) também demonstraram que as taxas de aumento da atividade da doença foram semelhantes entre os grupos. A análise econômica mostrou que a mudança do Remicade® para o Remsima™ trouxe economia de R$ 1,75 milhão de reais (0,5 milhão de dólares), com 1.689 ampolas de infliximabe dispensadas no período. Conclusão: A troca do medicamento Remicade® pelo Remsima™ nos pacientes com AR, EA e AP, no contexto do Planserv, demonstrou ter sido uma medida segura, eficaz e econômica.

Objective: Planserv offers coverage of biological therapy for rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PA). In August 2016, 78 patients were on Remicade® (infliximabe). At this date the value of Remicade® was reduced to the same value as Remsima™ (infliximabe biossimilar), with this all patients who were using Remicade® exchanged for Remsima™. We conducted a study to measure therapy discontinuity, and economics. Methods: An uncontrolled real-world study (prospective cohort) these patients who were using Remicade® and switched to Remsima™ between September 2016 and September 2017. The primary outcome was the discontinuation rate of treatment (for any cause). The secondary outcome was the "increased disease activity" rate as measured by the scores SDAI, BASDAI and CASPAR. It was as "increased disease activity", any measure higher than the initial, and that was above the remission limit of the disease. The reference values for "increased disease activity" were the historical measures. The economic impact measured by a cost minimization analysis. Results: In September 2017, 5 (6%) patients who switched from Remicade® to Remsima™, discontinued therapy (4 due to failure and 1 loss of follow-up). The reference discontinuation rate (Remicade®) was 11% (9% failure and 2% loss of follow-up). Subgroup analyzes (discontinuation of therapy by type of pathology) were equivalent. The rate of "increased disease activity" occurred in 42% of patients for Remsima™, and 46% for Remicade®. Subgroup analyzes (by type of pathology) also showed that rates of increase in disease activity were similar between groups. The economic analysis showed that the change from Remicade® to Remsima™ savings of R $ 1.75 million (US $ 0.5 million), with 1,689 ampoules of infliximabe dispensed in the period. Conclusion: The switching of Remicade® by Remsima™ in patients with RA, SA and PA in the context of Planserv, has been shown to be a safe, effective and economical measure.

Biosimilar etanercept: a real world safety and patient related outcomes from a single centre

Background: Biosimilars are expected to provide affordable and quality treatment equivalent to the biologics in various rheumatic disorders. Presently, the data available on the safety and effectiveness of biosimilars is very scarce. The objective of the present study was to assess the safety profile of intended biosimilar of etanercept developed by Intas pharmaceuticals Ltd. (Intacept) in Rheumatoid arthritis (RA), spondyloarthropathy (SpA), ankylosing Spondylitis (AS), juvenile idiopathic arthritis (JIA) and psoriatic arthritis (PsA).Methods: In single center, retrospective observational study, all patients were enrolled in routine clinical practice who received Intended biosimilar of Etanercept (Intacept) and the following data was collected. Basic demographic profile, disease and duration of therapy, any adverse event, patient’s global assessment of disease activity on visual analogue scale (0 to 100), patient’s overall experience with Intended biosimilar etanercept (Intacept).Results: Total 70 patients were enrolled (41males and 29 females) having RA (42), AS (11), SpA (13), JIA (2) AND PsA (2). The mean duration of follow up was 8±1.7 months. 10% patients reported adverse events like injection site pain (4.29%), fever (2.86%), redness (1.42%) and weight gain (1.42%). 45% patients had LTBI screen positive and were initiated on chemoprophylaxis with Rifampicin and INH 4weeks prior to Intacept. About 24% of patients dropped due to various reasons like affordability issue (5.7%), inadequate response (8.6%), no response (10%) and side effects (5.7%). 51.4% patients observed more than 50% improvement in global disease activity with Intacept while 10% patients did not get any response with the treatment. 77.2% patients perceived the overall therapy with Intacept as excellent, very good, good or OK while 22.8% patients rated Intacept therapy as non-satisfactory.Conclusions: The study leads to the conclusion that Intended biosimilar of etanercept (Intacept) was safe and well tolerated in various rheumatic disorders in a real-world scenario.

The discussion on a proposed quality similarity assessment criteria of rituximab biosimilar / 药学学报

Recently, biosimilar antibodies have become a mainstream component of the biopharmaceutical industry in China. The principle requirements for the development and evaluation of biosimilars are based on proving similarity in product quality (analytical similarity) between a proposed biosimilar candidate and the originator reference drug. However, because the quality of a reference drug often varies during the life cycle and not all reference drug samples are able to collected by a biosimilar sponsor, it has not been practical to accurately determine the critical quality attributes as well as an accurate control range through the characterization of the limited number of reference drug lots that are typically collected. Therefore, the development and evaluation of biosimilars has been challenging both for industry and regulatory agencies. In this article, The Chemistry, Manufacturing and Control (CMC) dossier of the rituximab originator company and the dossiers of 18 biosimilar companieswere retrospectively analyzed. Furthermore, the assessment criteria to determine quality similarity of rituximab biosimilar candidates have been proposed, which criteria have been used by reviewing the physicochemical and biological properties data obtained from 123 lots of the reference drug. Moreover, some case studies have been provided that illustrate the application of the proposed analytical similarity criteria in the practice of drug evaluation.

Knowledge and Viewpoints on Biosimilar Monoclonal Antibodies among Asian Physicians: Comparison with European Physicians / 대한소화기학회지

BACKGROUND/AIMS: Current knowledge and viewpoints regarding biosimilars among physicians in Asia are unknown, even though these were investigated by European Crohn's and Colitis Organization (ECCO) members in 2013 and 2015. Thus, this study conducted a multinational survey to assess the awareness of biosimilar monoclonal antibodies among Asian physicians.METHODS: A 17-question multiple-choice anonymous web survey was conducted with the logistic support of the Asian Organization of Crohn's and Colitis (AOCC). Randomly selected AOCC members were invited by e-mail to participate between February 24, 2017 and March 26, 2017.RESULTS: In total, 151 physicians from eight Asian countries responded to the survey. Most of the participants were gastroenterologists (96.6%), and 77.5% had cared for inflammatory bowel diseases (IBD) patients for more than 5 years. The majority of the respondents (66.2%) were aware that a biosimilar is similar but not equivalent to the originator. The majority of respondents (77.5%) considered cost saving to be the main advantage of biosimilars, but a high percentage of respondents (38.4%) were concerned about a different immunogenicity from that of the originator (92.4% and 27.1% respectively in ECCO 2015). Only 19.2% considered that the originator and biosimilars were interchangeable, and only 6.0% felt very confident in the use of biosimilars (44.4% and 28.8% respectively in ECCO 2015).CONCLUSIONS: Asian gastroenterologists in 2017 are generally well informed about biosimilars. On the other hand, compared to the ECCO members surveyed in 2015, Asian gastroenterologists had more concerns and less confidence about the use of biosimilars in clinical practice. Thus, IBD-specific data on the comparison of the efficacy, safety, and immunogenicity in Asian patients are needed.