Cost per responder of adalimumab biosimilars versus methotrexate in patients with psoriasis: a real-life experience.

BACKGROUND: Pharmacoeconomic studies examining the cost-effectiveness of adalimumab biosimilars versus methotrexate in real-life settings are limited. OBJECTIVES: To assess the cost per responder from the perspective of the National Health System of adalimumab biosimilars versus methotrexate for psoriasis treatment in a real-life setting. METHODS: A cost-per responder analysis comparing adalimumab biosimilars MSB11022 (Idacio®) and ABP 501 (Amgevita) versus subcutaneous methotrexate was performed. The incremental cost per responder was calculated by multiplying the cost of treatment (including the discounts, as published in the framework agreement of the Veneto region) and the number needed to treat each therapy. The clinical efficacy measures were defined as being on treatment (i.e., retention rate) at weeks 24 and 52. RESULTS: A total of 712 adult patients with moderate-to-severe chronic plaque psoriasis consecutively admitted to the outpatient clinic from January 2021 to December 2022 were included; 160 were treated with ABP 501 (Amgevita), 250 with MSB11022 (Idacio) and 302 with methotrexate. The retention rates of Amgevita, Idacio and methotrexate at week 24 were 86%, 90% and 78%, and 81%, 82% and 63% at week 52, respectively. The cost per responder at week 24 was €674 for Amgevita, €366 for Idacio and €264 for methotrexate, respectively; at week 52, was €1430 for Amgevita® €799 for Idacio® and €652 for methotrexate, respectively. CONCLUSIONS: The real-life cost-effectiveness of biosimilar drugs is largely influenced by discount rates. The week 52 cost-effectiveness of Idacio is comparable to subcutaneous methotrexate. The lowering of the cost of biosimilar drugs makes them a more accessible therapeutic option and they also can be introduced earlier in the treatment of moderate-to-severe psoriasis.

The Perception among Israeli Gastroenterologists Regarding Treatment of Patients with Biosimilar Medications.

Background and Objectives: The ever-expanding entry of biosimilar drugs into the Israeli market requires doctors to decide whether to prescribe these medications. We aimed to assess the prevalence of biosimilar use and Israeli gastroenterologists' knowledge, experience, and perception of biosimilar treatment. Materials and Methods: A cross-sectional survey was conducted among Israeli Gastroenterology Association (IGA) members between March and May 2022 using a structured 20-item questionnaire. Results: The questionnaire was completed by 108 gastroenterologists. Sixty-two percent prescribed biosimilars to their patients in the past year. Most of the patients (81%) were biologically naïve and only 19% were switched to a biosimilar. Most gastroenterologists (75%) answered that the effectiveness is the same. The rates of resistance to switching were 19%, 36%, and 70% for patients in remission for over two years, pregnant women, and difficulty reaching remission, respectively. In cases seeing a lack of response after switching, most physicians chose to change the mechanism of action, with only a small percentage returning to the brand-name drug. Conclusions: Most Israeli gastroenterologists are not concerned about biosimilars' safety and efficacy. Despite this, most physicians will prefer the brand-name drug, especially regarding adalimumab. The populations in which physicians most oppose switching are those who have had difficulty achieving remission and pregnant women.

A Framework for Evaluating the Implementation of Biosimilar Drugs.

Background: The introduction of biosimilar drugs has significant effects on health care systems, and a variety of approaches are required to support acceptance, adoption, and use of these drugs. Literature exists on the enablers of, and barriers to, biosimilar implementation, but frameworks that support the evaluation of biosimilar implementation strategies are currently lacking. Objective: To develop an evaluation framework for assessing the effects of biosimilar implementation strategies on patients, clinicians, and publicly funded drug programs. Methods: The scope of the evaluation was determined by a pan-Canadian working group through the creation of a logic model of activities and expected outcomes associated with biosimilar implementation. Each component of the logic model was considered under the RE-AIM framework, which led to a set of evaluation questions and indicators. Feedback to inform the final framework was sought from stakeholders through focus group sessions and written responses. Results: An evaluation framework was created that articulates evaluation questions and indicators across 5 priority areas: stakeholder engagement, patient experience, patient outcomes, clinician experience, and system sustainability and affordability. Stakeholder feedback was obtained through 9 focus group sessions with a total of 87 participants. Feedback was used to refine the framework on the basis of stakeholder priorities and feasibility. Conclusions: Through extensive stakeholder consultation, an evaluation framework was developed to measure and monitor the effects of biosimilar implementation on the 5 identified priority areas, as well as to inform future biosimilar implementations. This framework can be used as a starting point for evaluating the implementation of biosimilars across health care systems.

Contexte: L'apparition de médicaments biosimilaires a eu et continue d'avoir des effets importants sur les systèmes de soins de santé et diverses approches doivent être mises en place pour qu'ils soient acceptés, adoptés et utilisés. Il existe de la documentation sur les catalyseurs et les obstacles à leur mise en œuvre, mais les cadres entourant l'évaluation des stratégies de mise en œuvre des médicaments biosimilaires font actuellement défaut. Objectif: Développer un cadre d'évaluation pour estimer les retombées des stratégies de mise en œuvre des biosimilaires sur les patients, les cliniciens et les programmes de médicaments financés par les deniers publics. Méthodes: Un groupe de travail pancanadien a déterminé la portée de l'évaluation à l'aide d'un modèle logique des activités et des résultats attendus associés à la mise en œuvre des biosimilaires. Chaque composante du modèle logique a été examinée dans le cadre RE-AIM, ce qui a donné lieu à un ensemble de questions d'évaluation et des indicateurs d'évaluation. Des commentaires pour éclairer le cadre final ont été sollicités auprès des parties prenantes au moyen de groupes de discussion et de réponses écrites. Résultats: Un cadre d'évaluation a été défini. Il articule les questions d'évaluation et des indicateurs d'évaluation dans 5 domaines prioritaires: l'engagement des intervenants, l'expérience des patients, les résultats des patients, l'expérience des cliniciens et la durabilité et l'abordabilité du système. Les commentaires des intervenants ont été obtenus au cours de 9 séances de groupes de discussion avec un total de 87 participants. Les commentaires ont été utilisés pour affiner le cadre sur la base des priorités des parties prenantes et de la faisabilité. Conclusions: Une vaste consultation des parties prenantes a permis de définir un cadre d'évaluation pour mesurer et surveiller les effets de la mise en œuvre des biosimilaires sur les 5 domaines prioritaires identifiés, ainsi que pour éclairer les futures mises en œuvre des biosimilaires. Ce cadre peut être utilisé comme point de départ pour évaluer la mise en œuvre des biosimilaires dans les systèmes de soins de santé.

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.

The current status of biological treatment for uveitis.

INTRODUCTION: Noninfectious uveitis represents one of the leading causes of blindness in developed Countries, compromising patients' quality of life and social functioning. The main treatment goals are the control of ocular inflammation, to avert and treat sight-threatening complications, thus preserving and/or restoring visual function. AREAS COVERED: This manuscript deals with systemic therapy with biologic drugs for noninfectious uveitis. An extensive literature search in the MEDLINE database (via PubMed) has been performed up to June 2020. The major classes of biologic molecules employed in ocular inflammatory diseases have been reviewed, focusing on TNF inhibitors, IL-1, IL-6, IL-17, IL-23 inhibitors, interferons, rituximab, and abatacept efficacy and safety. An overview of most recent developments in the field has been provided as well, with reference to the experience with JAK inhibitors and with biosimilar drugs. EXPERT OPINION: The development of the concept of targeted therapy and the subsequent introduction of biologic molecules in clinical practice have revolutionized the prognosis of uveitis. The target of a rapid and sustained steroid-free remission of ocular inflammation should be pursued for all patients early in the disease course, in order to have a better chance to improve the final visual outcome.

Perception of hematologists and oncologists about the biosimilars: A prospective Tunisian study based on a survey.

INTRODUCTION: Biosimilar drugs have significantly shaken the global pharmaceutical market through a better access to the health care services. The aim of this study is to establish a state of play in Tunisia based on the knowledge and perceptions of doctors on biosimilars in order to identify the problems related to these drugs and to propose solutions for improvement. MATERIALS AND METHODS: In our study, we conducted a prospective, descriptive survey using a questionnaire, destinated to oncologists and hematologists with different grades, from both public and private sectors and from several regions. The questions focused on physicians' general knowledge of biosimilars and their comparison with reference on safety, quality, efficacy, and indication. Finally, we explored the proportion of physicians who are favorable to the policy encouraging biosimilar use. RESULTS: One hundred and seven doctors among 150 answered the questionnaire; 57% were oncologists and 43% were hematologists. About one over five physicians defines biosimilar as a chemical drug. About 29% do not differentiate between a biosimilar and a generic one. A percentage of 68 believe that a biosimilar can have all the indications of its reference following complementary clinical studies. On the other side, 68.2% support the policy encouraging these drugs. Last, only 3.7% of the practitioners believe that they are well informed about biosimilars. DISCUSSION: Our results are comparable to other surveys described in the literature. However, this is the first study that targets oncologists and hematologists specifically. CONCLUSION: Our study showed a lack of information from oncologists and hematologists about biosimilars in Tunisia. Thus, health authorities should carry out training programs on biosimilars and introduce clear and effective legislation in order to allow better access to health care services.

Biosimilar biological drugs in the treatment of inflammatory bowel diseases.

Within the last 20 years, tumour necrosis factor inhibitors have been proven to be effective in achieving and maintaining clinical and endoscopic remission in patients with Crohn's disease and ulcerative colitis. Since 2013, when infliximab originator lost its patent protection, patients with inflammatory bowel diseases (IBDs) in Poland have also been treated with biosimilar drugs. Biosimilars are drugs with high similarity to their reference products in terms of physicochemical properties, including structure, safety, and efficacy. Biosimilars are approved for use on the basis of the same rigorous quality standards as their reference products. In 2018, also biosimilars of adalimumab have become available. Studies published to date have shown that biosimilars do not differ from reference drugs in terms of the efficacy and safety. There are numerous data to confirm that a single switch of biological drugs (mainly from reference to biosimilar drugs) has no effect on therapy efficacy and safety. However, a significantly lower cost of therapy with biosimilars not only allows us to treat a much larger number of patients but may also necessitate multiple switches from reference drugs to biosimilars (including biosimilars produced by different manufacturers). Recently, the first results have been published concerning multiple switches in patients with psoriasis and rheumatoid arthritis. However, no such data are currently available for patients with IBDs.

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.

Biosimilar monoclonal antibodies (mAbs) in oncology.

Biological medicines are derived from living cells and organisms. Monoclonal antibodies (mAbs) are biological agents that are widely used to treat malignancies including non-Hodgkin's lymphomas and chronic lymphocytic leukaemia. They are effective but expensive. The patents for many mAbs are expiring, so biosimilar medicines, which contain a version of the active ingredient of the original drug, are being developed. Biological medicines cannot be assessed in the same way as standard generic medications because they are difficult to copy and can change over time. A pathway regulates how biosimilars are assessed and compared with the original drug to ensure they are highly similar and have no clinically meaningful differences in terms of structure, function, pharmacodynamics and mechanism of action, pharmacokinetic properties, clinical efficacy and safety. Truxima® ▾(rituximab), the first biosimilar monoclonal antibody to be approved for use in the UK in an oncology setting, is biosimilar to intravenous (IV) rituximab; rituximab improves the effectiveness of standard chemotherapy for lymphoma. The two drugs are comparable in efficacy and safety and have the same indications, dosing regimen and storage procedures.

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¯).

A budget impact model for biosimilar infliximab in Crohn's disease in Bulgaria, the Czech Republic, Hungary, Poland, Romania, and Slovakia.

OBJECTIVES: To estimate the budget impact of the introduction of biosimilar infliximab for the treatment of Crohn's disease (CD) in Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. METHODS: A 3-year, prevalence-based budget impact analysis for biosimilar infliximab to treat CD was developed from third-party payers' perspective. The model included various scenarios depending on whether interchanging originator infliximab with biosimilar infliximab was allowed or not. RESULTS: Total cost savings achieved in biosimilar scenario 1 (interchanging not allowed) and BSc2 (interchanging allowed in 80% of the patients) were estimated to €8.0 million and €16.9 million in the six countries. Budget savings may cover the biosimilar infliximab therapy for 722-1530 additional CD patients. CONCLUSIONS: Introduction of biosimilar infliximab to treat CD may offset the inequity in access to biological therapy for CD between Central and Eastern European countries.

Doctors commitment and long-term effectiveness for cost containment policies: lesson learned from biosimilar drugs.

BACKGROUND: Agency is a pervasive feature of the health care market, with doctors acting as agents for both patients and the health care system. In a context of scarce resources, doctors are required to take opportunity cost into account when prescribing treatments, while cost containment policies cannot overlook their active role in determining health care resource allocation. This paper addresses this issue, investigating the effects of cost containment measures in the market of biosimilar drugs that represent a viable and cost-saving strategy for the reduction of health care expenditure. The analysis focuses on a particular region in Italy, where several timely policies to incentivize biosimilar prescribing were launched. METHODS: Drugs were identified by the anatomical therapeutic chemical classification system. Information about biosimilar drugs and their originator biological products was extracted from the IMS Health regional database. Drug consumption was expressed in terms of counting units, while expenditure was evaluated in Euro (€). The market penetration of biosimilars was analyzed by year and quarterly. RESULTS: In the Campania region of Italy, the effects of cost containment policies, launched between 2009 and 2013, showed the prescription of biosimilars strongly increasing in 2010 until prescribing levels reached and exceeded the market share of the reference biological products in 2012. After a slight reduction, a plateau was observed at the beginning of 2013. At the same time, the use of the originator products had been decreasing until the first quarter of 2011. However, after a 1-year plateau, this trend was reversed, with a new increase in the consumption of the originators observed. CONCLUSION: Results show that the cost containment policies, applied to cut health expenditure "to cure and not to care", did not produce the cultural change necessary to make these policies effective in the long run. Therefore, top-down policies for cost containment are not successful; rather, a bottom-up approach based on consensus among professionals should become the preferred option.