Therapeutic Equivalence of Biosimilar and Reference Biologic Drugs in Rheumatoid Arthritis: A Systematic Review and Meta-analysis.

Importance: Biosimilar drugs are potentially lower-cost versions of biologics that may improve access to therapy. However, there is a lack of adequate systematic reviews demonstrating equivalence between these drugs for the treatment of rheumatoid arthritis (RA). Objectives: To assess the efficacy, safety, and immunogenicity associated with biosimilars of adalimumab, etanercept, and infliximab compared with their reference biologics in patients with RA. Data Sources: MEDLINE via PubMed, Embase, Cochrane Central Register of Controlled Trials, and LILACS databases were searched from inception to September 2021. Study Selection: Head-to-head randomized clinical trials (RCTs) of biosimilars of adalimumab, etanercept, and infliximab and their biologic reference drugs for RA were assessed. Data Extraction and Synthesis: Two authors independently abstracted all data. Meta-analysis was conducted with bayesian random effects using relative risks (RRs) for binary outcomes and standardized mean differences (SMDs) for continuous outcomes, with 95% credible intervals (CrIs) and trial sequential analysis. Specific domains were assessed for the risk of bias in equivalence and noninferiority trials. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Main Outcomes and Measures: Equivalence was tested using prespecified margins for the American College of Rheumatology criteria, with at least 20% improvement in the core set measures (ACR20) (ie, RR, 0.94 to 1.06), and for the Health Assessment Questionnaire-Disability Index (HAQ-DI) (ie, SMD, -0.22 to 0.22). Secondary outcomes included 14 items measuring safety and immunogenicity. Results: A total of 25 head-to-head trials provided data on 10 642 randomized patients with moderate to severe RA. Biosimilars met equivalence with reference biologics in terms of ACR20 response (24 RCTs with 10 259 patients; RR, 1.01; 95% CrI, 0.98 to 1.04; τ2 = 0.000) and change of HAQ-DI scores (14 RCTs with 5579 patients; SMD, -0.04; 95% CrI, -0.11 to 0.02; τ2 = 0.002) considering prespecified margins of equivalence. Trial sequential analysis found evidence for equivalence for ACR20 since 2017 and HAQ-DI since 2016. Overall, biosimilars were associated with similar safety and immunogenicity profiles compared with reference biologics. Conclusion and Relevance: In this systematic review and meta-analysis, biosimilars of adalimumab, infliximab, and etanercept were associated with clinically equivalent treatment effects compared with their reference biologics for the treatment of RA.

Health technology assessment of biosimilars worldwide: a scoping review.

BACKGROUND: Health technology assessment (HTA) should provide an assessment of a technology's effects on health and of the related social, economic, organisational and ethical issues. HTA reports on biosimilars can specifically assess their immunogenicity, their extrapolation to one or more conditions, and the risks of interchangeability and substitution. We aimed to complete a scoping review within the context of HTA organisations to synthesise HTA reports on biosimilars and to map the extension, scope and methodological practices. MAIN BODY: A scoping review methodology was applied. The sources for biosimilars HTA reports were database searches and grey literature from HTA organisation websites up to June 2019. HTA reports of biosimilars were classified as full HTA, mini-HTA or rapid reviews. Data were extracted and recorded on a calibrated predefined data form. We identified 70 HTA reports of biosimilars of 16 biologic products (65.71% in 2015-2018) produced by 13 HTA organisations from 10 countries; 2 full HTAs, 4 mini-HTAs and 64 rapid reviews met the inclusion criteria. Almost all the rapid reviews gave no information regarding any evidence synthesis method and approximately half of the rapid reviews did not appraise the risk of bias of primary studies or the overall quality of evidence. All full-HTAs and mini-HTAs addressed organisational, ethical, social and legal considerations, while these factors were assessed in less than half of the rapid reviews. The immunogenicity and extrapolation of one or more conditions were often considered. The majority of full-HTAs and mini-HTAs contained an assessment of switching and a discussion of an educational approach about biosimilars. No HTA report rejected the adoption/reimbursement of the biosimilar assessed. CONCLUSION: HTA of biosimilars are emerging in the context of HTA organisations and those that exist often duplicate reports of the same biosimilar. Most HTA reports of biosimilars do not conduct a systematic literature review or consider economic issues. No report has rejected the adoption/reimbursement of biosimilars. There is a need to standardise the minimum criteria for the development of HTA on biosimilars to ensure a better understanding and better decision-making.

Rational use of diagnostic tests for clinical decision making.

OBJECTIVE: To assist clinicians to make adequate interpretation of scientific evidence from studies that evaluate diagnostic tests in order to allow their rational use in clinical practice. METHODS: This is a narrative review focused on the main concepts, study designs, the adequate interpretation of the diagnostic accuracy data, and making inferences about the impact of diagnostic testing in clinical practice. RESULTS: Most of the literature that evaluates the performance of diagnostic tests uses cross-sectional design. Randomized clinical trials, in which diagnostic strategies are compared, are scarce. Cross-sectional studies measure diagnostic accuracy outcomes that are considered indirect and insufficient to define the real benefit for patients. Among the accuracy outcomes, the positive and negative likelihood ratios are the most useful for clinical management. Variations in the study's cross-sectional design, which may add bias to the results, as well as other domains that contribute to decreasing the reliability of the findings, are discussed, as well as how to extrapolate such accuracy findings on impact and consequences considered important for the patient. Aspects of costs, time to obtain results, patients' preferences and values should preferably be considered in decision making. CONCLUSION: Knowing the methodology of diagnostic accuracy studies is fundamental, but not sufficient, for the rational use of diagnostic tests. There is a need to balance the desirable and undesirable consequences of tests results for the patients in order to favor a rational decision-making approach about which tests should be recommended in clinical practice.

Rational use of diagnostic tests for clinical decision making

SUMMARY OBJECTIVE: To assist clinicians to make adequate interpretation of scientific evidence from studies that evaluate diagnostic tests in order to allow their rational use in clinical practice. METHODS: This is a narrative review focused on the main concepts, study designs, the adequate interpretation of the diagnostic accuracy data, and making inferences about the impact of diagnostic testing in clinical practice. RESULTS: Most of the literature that evaluates the performance of diagnostic tests uses cross-sectional design. Randomized clinical trials, in which diagnostic strategies are compared, are scarce. Cross-sectional studies measure diagnostic accuracy outcomes that are considered indirect and insufficient to define the real benefit for patients. Among the accuracy outcomes, the positive and negative likelihood ratios are the most useful for clinical management. Variations in the study's cross-sectional design, which may add bias to the results, as well as other domains that contribute to decreasing the reliability of the findings, are discussed, as well as how to extrapolate such accuracy findings on impact and consequences considered important for the patient. Aspects of costs, time to obtain results, patients' preferences and values should preferably be considered in decision making. CONCLUSION: Knowing the methodology of diagnostic accuracy studies is fundamental, but not sufficient, for the rational use of diagnostic tests. There is a need to balance the desirable and undesirable consequences of tests results for the patients in order to favor a rational decision-making approach about which tests should be recommended in clinical practice.

RESUMO OBJETIVO: Auxiliar os clínicos na interpretação adequada das evidências científicas de estudos que avaliam testes diagnósticos, de modo a permitir seu uso racional na prática clínica. MÉTODOS: Revisão narrativa da literatura dos principais conceitos, desenhos de estudo, interpretação adequada dos dados de acurácia diagnóstica e realização de inferências sobre o impacto do teste diagnóstico na prática clínica. RESULTADOS: A maioria da literatura que avalia o desempenho de testes diagnósticos utiliza como delineamento os estudos transversais. Ensaios clínicos randomizados, avaliando desfechos clínicos, que seriam considerados ideais, são escassos. Os estudos transversais mensuram desfechos de acurácia diagnóstica que são considerados indiretos e insuficientes para definir o real benefício para os pacientes. Dentre os desfechos, as razões de verossimilhança positiva e negativa são as mais úteis para a decisão da conduta clínica. Variações no delineamento transversal do estudo, que podem acrescentar vieses aos resultados, bem como outros domínios que contribuem para diminuir a confiabilidade dos achados, são discutidos, além de como extrapolar tais achados de acurácia em impacto e consequências consideradas importantes para o paciente. Aspectos sobre custos, tempo para a obtenção do resultado, preferências e valores dos pacientes devem, preferencialmente, participar da tomada de decisão. CONCLUSÃO: Conhecer a metodologia dos estudos de acurácia diagnóstica é fundamental, porém não suficiente, para o uso racional de testes diagnósticos. Há a necessidade de se ponderarem as consequências desejáveis e indesejáveis dos resultados dos testes para os pacientes, de modo a favorecer a tomada de decisão racional acerca de qual teste recomendar na prática clínica.

Health-related quality of life of patients of Brazilian primary health care.

OBJECTIVE: To analyze the Health-Related Quality of Life (HRQoL) of patients of the primary health care of the Brazilian Unified Health System (SUS) and its associated factors. METHODS: This is a cross-sectional study with data from the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Serviços, 2015 (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines - Services, 2015). Data were collected with a questionnaire that included the EuroQol 5 Dimensions (EQ-5D) instrument. Patients from the five regions of Brazil were interviewed. Multiple linear regression was used to analyze their Health-Related Quality of Life and its associated factors. RESULTS: Of the total of 8,590 patients, the most frequent dimensions were pain/discomfort (50.7%) and anxiety/depression (38.8%). About 10% of the patients reported extreme problems in these dimensions. The following factors were significantly associated with a worse quality of life: being female; having arthritis, osteoarthritis, or rheumatism; cerebrovascular accident; heart disease; depression; health self-assessment as poor or very poor; drinking alcoholic beverages once or more per month; dieting to lose weight, avoiding salt consumption, and reducing fat intake. Significant association was observed between a better quality of life and: living in the North and Southeast regions of Brazil; practicing physical activities; and having a higher educational level. No association was observed with factors related to the health services. CONCLUSIONS: The Health-Related Quality of Life of patients was influenced by demographic and socioeconomic factors that were related to health conditions and lifestyle, being useful to guide specific actions for promoting health and the integral care to patients of the Brazilian Unified Health System.

Access to medicines by patients of the primary health care in the Brazilian Unified Health System.

OBJECTIVE: To evaluate the access to medicines in primary health care of the Brazilian Unified Health System (SUS), from the patients' perspective. METHODS: This is a cross-sectional study that used data from the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Services, 2015 (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), conducted by interviews with 8,591 patients in cities of the five regions of Brazil. Evaluation of access to medicines used concepts proposed by Penshansky and Thomas (1981), according to the dimensions: availability, accessibility, accommodation, acceptability, and affordability. Each dimension was evaluated by its own indicators. RESULTS: For the "availability" dimension, 59.8% of patients reported having full access to medicines, without significant difference between regions. For "accessibility," 60% of patients declared that the basic health unit (UBS) was not far from their house, 83% said it was very easy/easy to get to the UBS, and most patients reported that they go walking (64.5%). For "accommodation," UBS was evaluated as very good/good for the items "comfort" (74.2%) and "cleanliness" (90.9%), and 70.8% of patients reported that they do not wait to receive their medicines, although the average waiting time was 32.9 minutes. For "acceptability," 93.1% of patients reported to be served with respect and courtesy by the staff of the dispensing units and 90.5% declared that the units' service was very good/good. For "affordability," 13% of patients reported not being able to buy something important to cover expenses with health problems, and 41.8% of participants pointed out the expense with medicines. CONCLUSIONS: Results show 70%-90% compliance, which is compatible with developed countries. However, access to medicines remains a challenge, because it is still heavily compromised by the low availability of essential medicines in public health units, showing that it does not occur universally, equally, and decisively to the population.

Access to medicines by patients of the primary health care in the Brazilian Unified Health System / Acesso aos medicamentos pelos usuários da atenção primária no Sistema Único de Saúde

ABSTRACT OBJECTIVE To evaluate the access to medicines in primary health care of the Brazilian Unified Health System (SUS), from the patients' perspective. METHODS This is a cross-sectional study that used data from the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Services, 2015 (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines), conducted by interviews with 8,591 patients in cities of the five regions of Brazil. Evaluation of access to medicines used concepts proposed by Penshansky and Thomas (1981), according to the dimensions: availability, accessibility, accommodation, acceptability, and affordability. Each dimension was evaluated by its own indicators. RESULTS For the "availability" dimension, 59.8% of patients reported having full access to medicines, without significant difference between regions. For "accessibility," 60% of patients declared that the basic health unit (UBS) was not far from their house, 83% said it was very easy/easy to get to the UBS, and most patients reported that they go walking (64.5%). For "accommodation," UBS was evaluated as very good/good for the items "comfort" (74.2%) and "cleanliness" (90.9%), and 70.8% of patients reported that they do not wait to receive their medicines, although the average waiting time was 32.9 minutes. For "acceptability," 93.1% of patients reported to be served with respect and courtesy by the staff of the dispensing units and 90.5% declared that the units' service was very good/good. For "affordability," 13% of patients reported not being able to buy something important to cover expenses with health problems, and 41.8% of participants pointed out the expense with medicines. CONCLUSIONS Results show 70%-90% compliance, which is compatible with developed countries. However, access to medicines remains a challenge, because it is still heavily compromised by the low availability of essential medicines in public health units, showing that it does not occur universally, equally, and decisively to the population.

RESUMO OBJETIVO Avaliar o acesso aos medicamentos na Atenção Primária em Saúde do Sistema Único de Saúde na perspectiva do usuário. MÉTODOS Estudo transversal que utilizou dados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional no Brasil - Serviços, 2015, realizado por meio de entrevistas com 8.591 usuários em municípios das cinco regiões do Brasil. A avaliação do acesso aos medicamentos utilizou conceitos propostos por Penshansky e Thomas (1981), segundo as dimensões: disponibilidade, acessibilidade geográfica, adequação, aceitabilidade e capacidade aquisitiva. Cada uma das dimensões foi avaliada por meio de indicadores próprios. RESULTADOS Para dimensão disponibilidade, 59,8% dos usuários declararam ter acesso total aos medicamentos, sem diferença significante entre regiões. Para acessibilidade geográfica, 60% dos usuários declararam que a unidade básica de saúde não ficava longe de sua residência, 83% afirmaram ser muito fácil/fácil chegar até a unidade e a maioria dos usuários relatou caminhar (64,5%). Para adequação, a unidade foi avaliada como muito bom/bom para os itens conforto (74,2%) e limpeza (90,9%), e 70,8% dos usuários relataram não ter de esperar para retirar seus medicamentos, embora o tempo médio de espera tenha sido 32,9 minutos. Para aceitabilidade: 93,1% dos usuários relataram ser atendidos com respeito e cortesia pelos funcionários das unidades dispensadoras e 90,5% declararam ser muito bom/bom o atendimento das unidades. Para capacidade aquisitiva 13% dos usuários relataram ter deixado de comprar algo importante para cobrir gastos com problemas de saúde, 41,8% dos participantes apontaram a despesa com medicamentos. CONCLUSÕES Os resultados mostram 70%-90% de conformidade, compatível com países desenvolvidos. No entanto, o acesso aos medicamentos continua sendo um desafio pois ainda é fortemente comprometido pela baixa disponibilidade de medicamentos essenciais em unidades públicas de saúde, demonstrando que não ocorre de forma universal, equânime e resolutiva à população.

Health-related quality of life of patients of Brazilian primary health care / Qualidade de vida relacionada à saúde dos usuários da atenção primária no Brasil

ABSTRACT OBJECTIVE To analyze the Health-Related Quality of Life (HRQoL) of patients of the primary health care of the Brazilian Unified Health System (SUS) and its associated factors. METHODS This is a cross-sectional study with data from the Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Serviços, 2015 (PNAUM - National Survey on Access, Use and Promotion of Rational Use of Medicines - Services, 2015). Data were collected with a questionnaire that included the EuroQol 5 Dimensions (EQ-5D) instrument. Patients from the five regions of Brazil were interviewed. Multiple linear regression was used to analyze their Health-Related Quality of Life and its associated factors. RESULTS Of the total of 8,590 patients, the most frequent dimensions were pain/discomfort (50.7%) and anxiety/depression (38.8%). About 10% of the patients reported extreme problems in these dimensions. The following factors were significantly associated with a worse quality of life: being female; having arthritis, osteoarthritis, or rheumatism; cerebrovascular accident; heart disease; depression; health self-assessment as poor or very poor; drinking alcoholic beverages once or more per month; dieting to lose weight, avoiding salt consumption, and reducing fat intake. Significant association was observed between a better quality of life and: living in the North and Southeast regions of Brazil; practicing physical activities; and having a higher educational level. No association was observed with factors related to the health services. CONCLUSIONS The Health-Related Quality of Life of patients was influenced by demographic and socioeconomic factors that were related to health conditions and lifestyle, being useful to guide specific actions for promoting health and the integral care to patients of the Brazilian Unified Health System.

RESUMO OBJETIVO Analisar a qualidade de vida relacionada à saúde dos usuários da atenção primária em saúde do Sistema Único de Saúde e fatores a ela associados. MÉTODOS Estudo transversal com dados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos - Serviços, 2015. A coleta de dados foi por meio de questionário que incluiu o instrumento Euroqol 5 Dimensions. Foram entrevistados usuários das cinco regiões do Brasil. Regressão linear múltipla foi utilizada para analisar a qualidade de vida relacionada à saúde e fatores associados. RESULTADOS Do total de 8.590 usuários, as dimensões com maior frequência foram dor/mal-estar (50,7%) e ansiedade/depressão (38,8%). Cerca de 10% dos usuários reportaram problemas extremos nessas dimensões. Os fatores significantemente associados à pior qualidade de vida foram: ser do sexo feminino; ter artrite, artrose ou reumatismo; acidente vascular encefálico; doenças do coração; depressão; relatar autopercepção de saúde ruim/muito ruim; usar bebida alcoólica uma vez ou mais por mês; fazer dietas para perder peso, evitar o consumo de sal e reduzir o consumo de gordura. Foi observada associação significante entre uma melhor qualidade de vida e: residir no Norte e Sudeste; praticar atividades físicas e nível educacional mais alto. Não foi observada associação com fatores relacionados aos serviços de saúde. CONCLUSÕES A qualidade de vida relacionada à saúde dos usuários foi influenciada por fatores demográficos, socioeconômicos, relacionados às condições de saúde e ao estilo de vida, sendo útil para nortear ações específicas de promoção da saúde e cuidado integral à saúde dos usuários do Sistema Único de Saúde.