Efficacy/effectiveness and safety of emicizumab prophylaxis of people with hemophilia A: a systematic review and meta-analysis.

BACKGROUND: Emicizumab is a monoclonal antibody approved for prophylaxis against bleeds for people with hemophilia A (PwHA). A systematic review was conducted evaluating the efficacy/effectiveness and the safety of emicizumab as prophylaxis for PwHA compared to prophylaxis with factor VIII (FVIII) or bypassing agents (BPA), respectively in patients without and with inhibitors. RESEARCH DESIGN AND METHODS: Database-directed search strategies were performed in Aug/26/2022 and updated in Mar/16/2023. Studies evaluating the prophylaxis with emicizumab versus prophylaxis with FVIII or BPA in PwHA without or with inhibitors, respectively, were selected by two independent reviewers. Data were extracted by two independent reviewers. Annualized bleeding rates for total treated bleeding events (ABR-all) were evaluated by meta-analysis. The quality of studies and certainty of evidence were assessed. RESULTS: A total of 11 studies were included. The standard mean differences for ABR-all were -0.6 (95%CI -1.0 to -0.2, p-value = 0.0002), among PwHA without inhibitors, and -1.7 (95%CI -2.4 to -0.9, p-value <0.00001), among PwHA with inhibitors. However, there was moderate heterogeneity in both meta-analyses. The most frequent adverse event was injection site reaction. CONCLUSIONS: Emicizumab prophylaxis was superior in reducing the ABR-all when compared with prophylaxis with FVIII or BPA.

Emicizumab prophylaxis for people with hemophilia A: Waste estimation and the Brazilian perspective.

Costs of hemophilia A treatment are increasing. Waste of clotting products should be avoided. To estimate the first-year waste of emicizumab prophylaxis for people with hemophilia A and inhibitors (PwHAi) who failed immune tolerance induction (ITI), in Brazil. We evaluated the manufacturer and the Brazilian Ministry of Health (MoH) protocol-recommended regimens in a budget impact model. The loading dose consisted of 3.0 mg/kg/Q1W for 4 weeks, for both recommendations. The manufacturer maintenance regimens comprised 1.5 mg/kg/Q1W, 3.0 mg/kg/Q2W, and 6.0 mg/kg/Q4W. The MoH protocol maintenance regimen encompassed a hybrid Q1W/Q2W administration, depending on the body weight. The Q4W regimen was not recommended by the MoH protocol. Analyses were performed to estimate waste given its expense based on the World Health Organization body weight range (percentiles [P] 15, 50, and 85). The first-year emicizumab waste was estimated individually and for the disclosed PwHAi who failed ITI (n = 114). The highest emicizumab waste was estimated for the lowest body weights and the Q1W regimen. The Q4W regimen resulted in the lowest emicizumab waste, followed by the MoH protocol regimen. The total reconstituted costs estimated for the PwHAi who failed ITI according to the hybrid MoH protocol ranged from US$32,858,777 (P15) to US$47,186,858 (P85), with emicizumab waste ranging from 7.9 % (US$2,594,515) to 3.7 % (US$1,738,750), respectively. Lost resources due to current protocols for emicizumab prophylaxis for PwHAi who failed ITI in Brazil are considerable. Waste was more pronounced due to lower body weight and shorter administration intervals.

Economic Evaluation of Immune Tolerance Induction in Children With Severe Hemophilia A and High-Responding Inhibitors: A Cost-Effectiveness Analysis of Prophylaxis With Emicizumab.

OBJECTIVE: This study aimed to measure the cost-effectiveness of prophylaxis with emicizumab in PsHAhri on ITI in Brazil. METHODS: A cost-effectiveness modeling analysis was used to estimate the costs per PsHAhri on ITI and the number of prevented bleedings from undertaking one intervention (prophylaxis with BpA) over another (prophylaxis with emicizumab), based on the Brazilian Ministry of Health perspective. Costs of ITI with recombinant FVIII, prophylaxis with BpA or emicizumab, and treated bleeding episodes with BpA costs were evaluated for PsHAhri who had ITI success or failure. This study was conducted with the perspective of the Brazilian Ministry of Health (payer). RESULTS: During ITI, prophylaxis with BpA cost US $924 666/PsHAhri/ITI, whereas prophylaxis with emicizumab cost US $488 785/PsHAhri/ITI. During ITI, there was an average of 9.32 bleeding episodes/PsHAhri/ITI when BpA were used as prophylaxis and 0.67 bleeding/PsHAhri/ITI when emicizumab was used. By univariate deterministic sensitivity analysis, emicizumab remained dominant whichever variable was modified. CONCLUSION: In this study, prophylaxis with emicizumab during ITI is a dominant option compared with prophylaxis with BpA during ITI.

First-line biologic therapy with tumor necrosis factor inhibitors for psoriatic arthritis: a prospective observational study

ABSTRACT BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.

First-line biologic therapy with tumor necrosis factor inhibitors for psoriatic arthritis: a prospective observational study.

BACKGROUND: Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects multiple joints. It is associated with psoriasis and treated with synthetic and biologic drugs. OBJECTIVE: The objective of this study was to assess the outcomes of patients who received biologic therapy with tumor necrosis factor (TNF) inhibitors in terms of effectiveness, safety, functionality, and quality of life. DESIGN AND SETTING: A prospective observational study was performed at a single center in Belo Horizonte, Brazil. METHODS: Patients with PsA who received their first TNF inhibitor treatment were followed up for 12 months. Disease activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Clinical Disease Activity Index (CDAI). Functionality was measured using the Health Questionnaire Assessment (HAQ), and quality of life was evaluated using the European Quality of Life Five Dimensions (EQ-5D). Multiple linear regression was used to identify predictors of the clinical response at 12 months. RESULTS: A total of 143 patients treated with adalimumab or etanercept were evaluated. Most of the clinical measures were significantly improved at 12 months. However, 31%-51% of the patients did not achieve good clinical control. No differences were observed between adalimumab and etanercept, except for poor functionality at 12 months among patients treated with etanercept. The main predictors of a worse clinical response were female sex, etanercept use, poor functionality, or lower quality of life at baseline. The main adverse reactions were alopecia, headache, injection site reaction, sinusitis, flu, dyslipidemia, and infections. CONCLUSION: TNF inhibitor therapy was effective and safe. However, despite improvements in clinical measures, most patients did not achieve satisfactory control of the disease.

Conventional Synthetic Disease-Modifying Anti-rheumatic Drugs for Psoriatic Arthritis: Findings and Implications From a Patient Centered Longitudinal Study in Brazil.

Background: Conventional synthetic disease-modifying antirheumatic drugs are the first-line treatment to inhibit the progression of psoriatic arthritis. Despite their widespread clinical use, few studies have been conducted to compare these drugs for psoriatic arthritis. Methods: a longitudinal study was carried out based on a centered patient national database in Brazil. Market share of drugs, medication persistence, drug costs, and cost per response were evaluated. Results: a total of 1,999 individuals with psoriatic arthritis were included. Methotrexate was the most used drug (44.4%), followed by leflunomide (40.6%), ciclosporin (8.2%), and sulfasalazine (6.8%). Methotrexate and leflunomide had a greater market share than ciclosporin and sulfasalazine over years. Medication persistence was higher for leflunomide (58.9 and 28.2%), followed by methotrexate (51.6 and 25.4%) at six and 12 months, respectively. Leflunomide was deemed the most expensive drug, with an average annual cost of $317.25, followed by sulfasalazine ($106.47), ciclosporin ($97.64), and methotrexate ($40.23). Methotrexate was the drug being the lowest cost per response. Conclusion: Methotrexate had the best cost per response ratio, owing to its lower cost and a slightly lower proportion of persistent patients when compared to leflunomide. Leflunomide had a slightly higher medication persistence than methotrexate, but it was the most expensive drug.

Functionality assessment in patients with rheumatic diseases undergoing treatment in the Public Health System.

OBJECTIVE: To evaluate the therapeutic response (functionality) and its associated factors in patients on biological drugs on the Public Health System for treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. METHODS: An open prospective cohort was carried out from 2011 to 2019, in Belo Horizonte (MG). Functionality was assessed using the Health Assessment Questionnaire Disability-Index at baseline, and after 6 and 12 months of follow-up. Factors associated with poor functionality were identified through logistic regression. RESULTS: The median Health Assessment Questionnaire Disability-Index at baseline was 1.5 (interquartile range of 0.8-1.9), with poor functionality observed in patients with rheumatoid arthritis. Improved functionality was seen at 6 months of treatment for the three diseases. The predictors of poor functionality at 6 months for psoriatic arthritis and ankylosing spondylitis were female sex, low education levels, and high disease activity; and for rheumatoid arthritis and psoriatic arthritis were female sex, advanced age, and high disease activity. In 12 months, the three diseases had predictors of worse functionality: female sex, low education, and high disease activity. CONCLUSION: There was a significant improvement in functionality during the follow-up, with better response at 6 months of treatment. Poor functionality was observed in older, female patients, with low education and high disease activity.

Biological therapy in psoriatic arthritis patients with and without previous biologic experience / Terapia biológica em pacientes com artrite psoriásica com e sem experiência prévia no uso de medicamentos biológicos

Objective: this study evaluated the biological therapy effects on disease activity, functionality, quality of life, drug survival, and safety of patients with psoriatic arthritis naïve and experienced in biological therapy. Methods: a one-year prospective observational study was performed. The outcomes assessed were drug survival, disease activity, functionality, quality of life, and safety. Multiple linear regression was used to assess predictive factors for clinical re-sponse. Results: a total of 205 patients were included, 155 of whom were biologic naïve and 50 biologic experienced. Drug survival rate was greater for naïve patients than experienced patients at 6 months, but not at 12 months. Drug survival rates were 71.5% for naïve patients and 70.0% for experienced patients at 12 months. All clinical parameters improved for both biologic naïve and experienced patients. At 12 months, 63% of naïve patients and 52% of expe-rienced patients had an improvement in their quality of life. Besides, 48% of naïve patients and 42% of experienced patients had an improvement in functionality. The axial disease improved in 67% of naïve individuals and 56% of experienced patients. Good control of peripheral disease was achieved by 49% of naïve patients and 44% of experi-enced patients. Female sex, use of etanercept or infliximab, and lower functionality or quality of life at baseline were the main predictors of poor clinical response. Conclusion: Patients' health improved after starting biological therapy. In general, biologic experienced patients had more adverse reactions and lesser effectiveness (AU)

Objetivo: avaliar os efeitos da terapia biológica sobre a atividade da doença, funcionalidade, qualidade de vida, per-sistência no tratamento e segurança em pacientes com artrite psoriásica sem experiência e com experiência prévia em terapia biológica. Métodos: um estudo observacional prospectivo de um ano foi realizado. Os desfechos avaliados foram a persistência no tratamento, atividade da doença, funcionalidade, qualidade de vida e segurança. Um modelo de regressão linear múltipla foi utilizado para avaliar os fatores preditores de resposta clínica. Resultados: foram incluídos 205 pacientes, dos quais 155 não tinham e 50 tinham experiência prévia com medicamentos biológicos. As taxas de persistência no tratamento foram maiores para pacientes sem experiência prévia em comparação aos experientes em seis meses de acompanhamento, mas não em 12 meses. As taxas de persistência no tratamento foram 71,5% em pa-cientes sem experiência prévia e 70% em pacientes com experiência prévia em 12 meses. Todos os desfechos clínicos avaliados melhoraram em ambos os grupos de pacientes. Aos 12 meses, 63% dos pacientes sem experiência prévia e 52% dos pacientes com experiência prévia apresentaram melhora na qualidade de vida. Além disso, 48% dos pacientes sem experiência prévia e 42% dos pacientes com experiência prévia apresentaram melhora na funcionalidade. A do-ença axial melhorou em 67% dos pacientes sem experiência prévia e em 56% dos pacientes com experiência prévia. Um bom controle da doença articular periférica foi observado em 49% dos pacientes sem experiência prévia e em 44% dos pacientes com experiência prévia. Os principais fatores preditores de pior resposta clínica foram sexo feminino, uso de etanercepte ou infliximabe, bem como pior funcionalidade e qualidade de vida no início do estudo. Conclusão:a saúde dos pacientes melhorou após o início do tratamento com os medicamentos biológicos. Em geral, pacientes com experiência prévia com medicamentos biológicos apresentaram mais reações adversas e menor efetividade (AU)

Economic evaluation of adalimumab versus etanercept for psoriatic arthritis in a Brazilian real-world model.

BACKGROUND: TNF inhibitors are costly drugs supplied generally on health systems or private insurances. Performance analysis is essential to verify the results achieved by health technologies in these systems. The objective of the study was to compare the two most used biological drugs for the treatment of psoriatic arthritis (PsA) in Brazil. METHODS: A cost-utility analysis was built using a Markov model, with a five-year time horizon, a discount rate of 5%, and from the perspective of the Unified Health System. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: Etanercept was the most cost-effective drug. Adalimumab became the most cost-effective drug in one of the four analysis scenarios with a willingness to pay from one gross domestic product per capita. The deterministic sensitivity analysis identified that the cost parameters had the greatest impact on the most effective drug. The probabilistic sensitivity analysis indicated that etanercept is the drug most likely to be cost-effective. CONCLUSION: The difference between the drugs in terms of utility was minimal and the costs were the main factor that impacted the cost-utility ratio, which points to the benefits of price renegotiation for the efficient allocation of resources in the health system.

Sixteen Years of Heart Transplant in an Open Cohort in Brazil: Analysis of Graft Survival of Patients using Immunosuppressants. / Dezesseis Anos de Transplante Cardíaco em Coorte Aberta no Brasil: Análise de Sobrevivência de Pacientes em Uso de Imunossupressores.

BACKGROUND: Heart transplant is the main therapeutic alternative for advanced heart failure patients. Several risk factors affect these patients' survival; however, few studies about the topic are available in Brazil. OBJECTIVES: To review the survival rates of heart transplant patients in the Brazilian Public Health System (Sistema Único de Saúde - SUS) between 2000 and 2015. METHODS: This is a non-concurrent, open cohort study, involving cardiac transplant patients in Brazil. The cumulative survival probability was estimated by the Kaplan-Meier curve, and the curve comparison was done using the Log-Rank test. The Cox model was used to calculate the Hazard-Ratio (HR). Analyses were conducted at the 95% confidence level. RESULTS: The heart transplant survival rate median in Brazil, during the period, was 8.3 years. Each additional year in the recipient's age, the occurrence of infections, and the performance of the surgical procedure in the South Region were associated with a higher risk of graft loss. A higher use ratio of immunosuppressants mycophenolate and azathioprine acted as a protection factor. CONCLUSIONS: The analyses conducted provide the first information about the median survival time in heart transplant patients in Brazil. The difference noticed among the geographical regions may be related to the different treatment protocols adopted in the country, especially in the early 2000s. The rate of mycophenolate and azathioprine use as a protection factor suggests that, despite the absence of differences among therapeutic strategies, use of these drugs may favor survival of certain patients. The study provides robust epidemiological data, which are relevant for public health.

FUNDAMENTO: O transplante cardíaco é a principal alternativa terapêutica para pacientes com insuficiência cardíaca avançada. Diversos fatores de risco influenciam a sobrevivência desses pacientes, entretanto, poucos estudos acerca do tema estão disponíveis no Brasil. OBJETIVOS: Analisar a sobrevivência de pacientes transplantados cardíacos pelo Sistema Único de Saúde no Brasil entre 2000-2015. MÉTODOS: Trata-se de uma coorte não concorrente, aberta, de pacientes transplantados cardíacos no Brasil. A probabilidade acumulada de sobrevivência foi estimada por Kaplan-Meier e a comparação entre as curvas realizada pelo Teste de Log-Rank. O modelo de Cox foi utilizado para calcular o Hazard-Ratio (HR). As análises foram realizadas ao nível de 95% de confiança. RESULTADOS: A mediana de sobrevivência do transplante cardíaco no Brasil no período foi 8,3 anos. Cada ano adicional na idade do receptor, a ocorrência de infecções e a realização do procedimento cirúrgico na região Sul relacionaram-se ao maior risco de perda do enxerto. Maior proporção de uso dos imunossupressores micofenolato e azatioprina atuou como fator protetor. CONCLUSÕES: As análises realizadas fornecem a primeira informação quanto ao tempo de sobrevivência mediana do transplante cardíaco no Brasil. A diferença observada entre as regiões pode estar relacionada aos diferentes protocolos de tratamento adotados no país, principalmente no início dos anos 2000. A proporção de uso de micofenolato e azatioprina como fator protetor sugere que, apesar de não haver diferença entre as estratégias terapêuticas, o uso desses medicamentos pode favorecer a sobrevida de determinados pacientes. O estudo apresenta dados epidemiológicos robustos e importantes para a saúde pública.

Cost-utility analysis of the anti-TNF therapy for rheumatoid arthritis in a real-world based model.

BACKGROUND: Spending on drugs provided by the Brazilian Public Health System (BPHS) for the treatment of rheumatoid arthritis (RA) increased substantially with the beginning of the supply of biological disease-modifying anti-rheumatic drugs (bDMARD). This study aims to perform a cost-utility analysis of the most used biological drugs for the treatment of RA in Brazil. METHODS: a Markov model was used to carry out the cost-utility analysis. The data were obtained from a prospective cohort of RA patients using adalimumab, etanercept, and golimumab in Brazil. The BPHS perspective was adopted and the time horizon was five years. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. RESULTS: golimumab was the most cost-effective drug. Etanercept was dominated by golimumab. Adalimumab presented an incremental cost-utility ratio (ICUR) of $95,095.37 compared to golimumab in five years of follow-up. These results were confirmed by sensitivity analyses. CONCLUSION: the utility among adalimumab, etanercept, and golimumab was similar and the cost was the component that most impacted the economic model. Therefore, depending on the agreed price with the drug manufacturers, the incremental cost-utility ratio may vary among them.

Real-world effectiveness of olanzapine and risperidone in the treatment of schizophrenia in Brazil over a 16-year follow-up period; findings and implications.

Introduction: Antipsychotics are widely prescribed for patients with schizophrenia. The Brazilian public health system provides these patients free of charge to patients and it is pertinent to evaluate their benefits.Objective: To evaluate the effectiveness of olanzapine and risperidone in the treatment of patients with schizophrenia in the real-world and assessing risk factors for their discontinuation through a national non-concurrent cohort with 16 years of follow-up.Methods: Three SUS administrative databases were integrated by deterministic-probabilistic linkage. After patients were matched (1:1) for psychiatric hospitalization, year of receiving the antipsychotic, sex, and age, considering either olanzapine or risperidone at study entry. Kaplan-Meier was used to estimate the cumulative probabilities of discontinuation of treatment and associated factors were identified. Sensitivity analyses were performed.Results: 3416 pairs of patients were included. Olanzapine had a longer time until discontinuation of treatment (p = 0.021), and risperidone had a higher risk of discontinuation (p = 0.021). Among patients persistent for at least 24 months, there was no statistically significant difference.Conclusion: Olanzapine demonstrated superior real-world effectiveness over risperidone, in terms of survival and psychiatric hospitalization. This superiority was not sustained in all analyses.

Risk factors associated with antineoplastic chemotherapy-induced nausea and vomiting.

OBJECTIVE: To estimate the incidence and to evaluate risk factors for antineoplastic nausea and vomiting with high and moderate emetogenic chemotherapy in adult patients in the first treatment cycle. METHODS: Prospective cohort study with follow-up of 269 adults during the first cycle of antineoplastic chemotherapy. The incidence of nausea and vomiting was evaluated in the acute phase (0-24 hours), in the late phase (24 hours-5th day) and in the total phase (0-5th day). RESULTS: In total, 152 patients underwent high emetogenic chemotherapy and 117 moderate emetogenic chemotherapy. The relative frequency of nausea was higher when compared with vomiting in the acute phase (p < 0.001) and in the late phase (p < 0.001). The risk factors identified were: age group ≤ 49 years (odds ratio = 0.47; 95%CI 0.23-0.95) and 50-64 years (odds ratio = 0.45; 95%CI 0.23-0.87), tobacco use (odds ratio = 0.35; 95%CI 0.14-0.88), and high emetogenic chemotherapy (odds ratio 0.55; 95%CI 0.31-0.95). CONCLUSION: The incidence of nausea was higher than that of vomiting, and adverse effects were more frequent in the late phase. The results suggest the risk factors for chemotherapy-induced nausea and vomiting are tobacco, age (young adults), and high emetogenic chemotherapy.

Effectiveness of first-line treatment for relapsing-remitting multiple sclerosis in Brazil: A 16-year non-concurrent cohort study.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMM) is a chronic, progressive, inflammatory and immune-mediated disease that affects the central nervous system and is characterized by episodes of neurological dysfunction followed by a period of remission. The pharmacological strategy aims to delay the progression of the disease and prevent relapse. Interferon beta and glatiramer are commonly used in the Brazilian public health system and are available to patients who meet the guideline criteria. The scenario of multiple treatments available and in development brings the need for discussion and evaluation of the technologies already available before the incorporation of new drugs. This study analyses the effectiveness of first-line treatment of RRMS measured by real-world evidence data, from the Brazilian National Health System (SUS). METHODS AND FINDINGS: We conducted a non-concurrent national cohort between 2000 and 2015. The study population consisted of 22,722 patients with RRMS using one of the following first-line drugs of interest: glatiramer or one of three presentations of interferon beta. Kaplan-Meier analysis was used to estimate the time to treatment failure. A univariate and multivariate Cox proportional hazard model was used to evaluate factors associated with treatment failure. In addition, patients were propensity score-matched (1:1) in six groups of comparative first-line treatments to evaluate the effectiveness among them. The analysis indicated a higher risk of treatment failure in female patients (HR = 1.08; P = 0,01), those with comorbidities at baseline (HR = 1.20; P<0,0001), in patients who developed comorbidities after starting treatment (i.e., rheumatoid arthritis-HR = 1.65; P<0,0001), those exclusive SUS patients (HR = 1.31; P<0,0001) and among patients using intramuscular interferon beta (IM ßINF-1a) (28% to 60% compared to the other three treatments; P<0,0001). Lower risk of treatment failure was found among patients treated with glatiramer. CONCLUSIONS: This retrospective cohort suggests that glatiramer is associated with greater effectiveness compared to the three presentations of interferon beta. When evaluating beta interferons, the results suggest that the intramuscular presentation is not effective in the treatment of multiple sclerosis.

Integrative Review of Managed Entry Agreements: Chances and Limitations.

BACKGROUND AND OBJECTIVE: Managed entry agreements (MEAs) consist of a set of instruments to reduce the uncertainty and the budget impact of new high-priced medicines; however, there are concerns. There is a need to critically appraise MEAs with their planned introduction in Brazil. Accordingly, the objective of this article is to identify and appraise key attributes and concerns with MEAs among payers and their advisers, with the findings providing critical considerations for Brazil and other high- and middle-income countries. METHODS: An integrative review approach was adopted. This involved a review of MEAs across countries. The review question was 'What are the health technology MEAs that have been applied around the world?' This review was supplemented with studies not retrieved in the search known to the senior-level co-authors including key South American markets. It also involved senior-level decision makers and advisers providing guidance on the potential advantages and disadvantages of MEAs and ways forward. RESULTS: Twenty-five studies were included in the review. Most MEAs included medicines (96.8%), focused on financial arrangements (43%) and included mostly antineoplastic medicines. Most countries kept key information confidential including discounts or had not published such data. Few details were found in the literature regarding South America. Our findings and inputs resulted in both advantages including reimbursement and disadvantages including concerns with data collection for outcome-based schemes. CONCLUSIONS: We are likely to see a growth in MEAs with the continual launch of new high-priced and often complex treatments, coupled with increasing demands on resources. Whilst outcome-based MEAs could be an important tool to improve access to new innovative medicines, there are critical issues to address. Comparing knowledge, experiences, and practices across countries is crucial to guide high- and middle-income countries when designing their future MEAs.

Polypharmacy, socioeconomic indicators and number of diseases: results from ELSA-Brasil.

OBJECTIVE: To estimate the prevalence of polypharmacy, describe the pharmacotherapeutic classes used, and investigate whether polypharmacy is associated with demographic and socioeconomic indicators, regardless of the number of diseases, among participants in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) baseline (2008-2010). METHOD: In this analysis, 14,523 adults and elderly (35-74 years) participated. Polypharmacy was characterized as regular use of five or more medicines. The demographic and socioeconomic indicators analyzed were: gender, age, education level, per capita family income, and access to private health insurance. The independent association between demographic and economic indicators and polypharmacy was estimated by binary logistic regression. RESULTS: The prevalence of polypharmacy was 11.7%. The most used drugs were those with action on the cardiovascular system. After adjustments, including by number of diseases, the chances of being on polypharmacy treatment were significantly higher among women, older participants and those with greatest number of diseases. Individuals without health insurance had lower chance to be under polypharmacy, as well as those with lower income. CONCLUSION: The occurrence of polypharmacy among ELSA-Brasil baseline participants was mainly due to drugs for the treatment of chronic diseases. The relation between polypharmacy and the female gender, as well as its association with old age, are in consonance with the results obtained in other studies. Despite the absence of an association between polypharmacy and education level, the income and health insurance results reinforce the existence of social inequalities regarding drug use.

Impact of biologic DMARDs on quality of life: 12-month results of a rheumatic diseases cohort using the Brazilian EQ-5D tariff.

OBJECTIVES: To evaluate the association between biological Disease-Modifying Anti-Rheumatic Drugs (bDMARDs) use and quality of life (QoL) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). PATIENTS AND METHODS: We evaluated adult patients prescribed biological DMARDs whose quality of life was evaluated at six and 12 months. The EuroQol 5 dimensions (EQ-5D) was used with the Brazilian tariff. RESULTS: Patients receiving bDMARDs had significant improvements in quality of life after 6 and 12 months (p < 0.001), regardless of the rheumatic condition and the therapeutic regimen (bDMARDs vs bDMARDs plus synthetic DMARDs) (ANCOVA; p > 0.05). At the end of one year, 62.6% of the participants presented significant clinical improvement in QoL. According to a sensitivity analysis, QoL results in the complete case analysis and in the multiple imputation model yielded similar conclusions. Patients with two or more comorbidities and worse QoL and disability status on baseline presented worse QoL at 12 months when compared to those with better disability status on baseline. Baseline clinical disease measured by activity indexes (BASDAI and CDAI) did not influence QoL after 12 months of bDMARD treatment. Pain and malaise were the EQ-5D domain that most influenced quality of life. CONCLUSION: Patients with rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis displayed significantly better QoL levels following treatment with DMARDs.

Use of medicines by adults in primary care: Survey on health services in Minas Gerais, Brazil. / Uso de medicamentos por adultos na atenção primária: inquérito em serviços de saúde de Minas Gerais, Brasil.

INTRODUCTION: Inappropriate use and increase of health care spending reinforce the need to extend our knowledge about the quality of medication use. OBJECTIVES: To describe and evaluate the profile of medication use in a representative sample of adult users of primary care services in the Unified Health System (SUS) of Minas Gerais. METHOD: Cross-sectional study, with 1,159 interviewees in 104 municipalities and 253 health care services. Data on sociodemographic characteristics, health conditions and use of medicines were collected, and these variables were stratified by age group. Univariate and multivariate analyses, using logistic regression, were conducted to identify predictors of self-medication. We set a significance level of 5% for all tests. RESULTS: The prevalence of medication use was 81.8%, with an average of 2.67 medicines per user, which increased with age. The most used drugs were losartan, hydrochlorothiazide and simvastatin, which differed between age groups. Significant self-medication was observed not only in young adults but also in the elderly. The predictors of self-medication were: being a young adult, having a higher level of education, not having chronic diseases, having worse self-perception of health and not adhering to prescription drugs. Young and elderly adults showed characteristics that made them more vulnerable in relation to the rational use of medicines. CONCLUSION: This study can contribute to improving primary care, where it identified problems related to the extent of medication use, especially among young adults and the elderly in Minas Gerais.

Effectiveness of Maintenance Immunosuppression Therapies in a Matched-Pair Analysis Cohort of 16 Years of Renal Transplant in the Brazilian National Health System.

The maintenance of patients with renal transplant typically involves two or more drugs to prevent rejection and prolong graft survival. The calcineurin inhibitors (CNI) are the most commonly recommended medicines in combinations with others. While immunosuppressive treatment regimens are well established, there is insufficient long-term effectiveness data to help guide future management decisions. The study analyzes the effectiveness of treatment regimens containing CNI after renal transplantation during 16 years of follow-up with real-world data from the Brazilian National Health System (SUS). This was a retrospective study of 2318 SUS patients after renal transplantion. Patients were propensity score-matched (1:1) by sex, age, type and year of transplantation. Kaplan-Meier analysis was used to estimate the cumulative probabilities of survival. A Cox proportional hazard model was used to evaluate factors associated with progression to graft loss. Multivariable analysis, adjusted for diabetes mellitus and race/color, showed a greater risk of graft loss for patients using tacrolimus plus mycophenolate compared to patients treated with cyclosporine plus azathioprine. In conclusion, this Brazilian real-world study, with a long follow-up period using matched analysis for relevant clinical features and the representativeness of the sample, demonstrated improved long-term effectiveness for therapeutic regimens containing cyclosporine plus azathioprine. Consequently, we recommend that protocols and clinical guidelines for renal transplantation should consider the cyclosporine plus azathioprine regimen as a potential first line option, along with others.

Comparative persistence of anti-tumor necrosis factor therapy in ankylosing spondylitis patients: a multicenter international study.

Objective: To evaluate persistence on conventional DMARDs (cDMARDs) and anti-TNF therapies, and to identify potential determinants of discontinuation among individuals with ankylosing spondylitis (AS) living in Brazil and Quebec, Canada.Methods: We conducted a cohort study of AS patients using health administrative data (2010-2015). One-year and 2-year persistence rates were assessed. Cox regression was used to identify potential determinants of therapy discontinuation.Results: One-year persistence was less likely in Brazil for both anti-TNF and cDMARDs (Brazil: 62.1 and 30.7%, Quebec: 66.9 and 67.0%). The 2-year persistence rates were lower for both anti-TNF and cDMARD, but remained higher in Quebec (Brazil: 47.9 and 18.1%, Quebec: 51.5 and 53.5%). In multivariate Cox regression analysis, age, sex and comorbidities were associated with persistence in both countries. In Quebec, persistence did not differ between rural and urban regions or with socioeconomic status. While in Brazil, patients in regions with higher Human Development Index and those in cities with lower Gini index were less likely to discontinue therapy.Conclusions: Canadian AS patients were more likely to persist on therapy compared to Brazilian patients, although rates were lower at 2 years in both countries. Socioeconomic disparity in persistence was found in Brazil, but not in Quebec.