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.

All-cause and cause-specific mortality among people with severe mental illness in Brazil's public health system, 2000-15: a retrospective study.

BACKGROUND: People with severe mental illness have a mortality rate higher than the general population, living an average of 10-20 years less. Most studies of mortality among people with severe mental illness have occurred in high-income countries (HICs). We aimed to estimate all-cause and cause-specific relative risk (RR) and excess mortality rate (EMR) in a nationwide cohort of inpatients with severe mental illness compared with inpatients without severe mental illness in a middle income country, Brazil. METHODS: This national retrospective cohort study included all patients hospitalised through the Brazilian Public Health System (Sistema Único de Saúde [SUS]-Brazil) between Jan 1, 2000, and April 21, 2015. Probabilistic and deterministic record linkages integrated data from the Hospital Information System (Sistema de informações Hospitalares) and the National Mortality System (Sistema de Informação sobre Mortalidade). Follow-up duration was measured from the date of the patients' first hospitalisation until their death, or until April 21, 2015. Severe mental illness was defined as schizophrenia, bipolar disorder, or depressive disorder by ICD-10 codes used for the admission. RR and EMR were calculated with 95% CIs, comparing mortality among patients with severe mental illness with those with other diagnoses for patients aged 15 years and older. We redistributed deaths using the Global Burden of Diseases, Injuries, and Risk Factors Study methodology if ill-defined causes of death were stated as an underlying cause. FINDINGS: From Jan 1, 2000, to April 21, 2015, 72 021 918 patients (31 510 035 [43·8%] recorded as male and 40 974 426 [56·9%] recorded as female; mean age 41·1 (SD 23·8) years) were admitted to hospital, with 749 720 patients (372 458 [49·7%] recorded as male and 378 670 [50·5%] as female) with severe mental illness. 5 102 055 patient deaths (2 862 383 [56·1%] recorded as male and 2 314 781 [45·4%] as female) and 67 485 deaths in patients with severe mental illness (39 099 [57·9%] recorded as male and 28 534 [42·3%] as female) were registered. The RR for all-cause mortality in patients with severe mental illness was 1·27 (95% CI 1·27-1·28) and the EMR was 2·52 (2·44-2·61) compared with non-psychiatric inpatients during the follow-up period. The all-cause RR was higher for females and for younger age groups; however, EMR was higher in those aged 30-59 years. The RR and EMR varied across the leading causes of death, sex, and age groups. We identified injuries (suicide, interpersonal violence, and road injuries) and cardiovascular disease (ischaemic heart disease) as having the highest EMR among those with severe mental illness. Data on ethnicity were not available. INTERPRETATION: In contrast to studies from HICs, inpatients with severe mental illness in Brazil had high RR for idiopathic epilepsy, tuberculosis, HIV, and acute hepatitis, and no significant difference in mortality from cancer compared with inpatients without severe mental illness. These identified causes should be addressed as a priority to maximise mortality prevention among people with severe mental illness, especially in a middle-income country like Brazil that has low investment in mental health. FUNDING: Bill and Melinda Gates Foundation, Fundação de Amparo a Pesquisa do Estado de Minas Gerais, FAPEMIG, and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil.

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.

A demographic and clinical panorama of a sixteen-year cohort of soft tissue sarcoma patients in Brazil.

Little is known about soft tissue sarcomas (STS) in Brazil, once the federal statistics regarding estimates on incidence and mortality of the most common cancers that affect the Brazilian population currently do not include STS. This study aims to perform a broad evaluation and description of the epidemiological profile, access to treatment and main clinical outcomes of the Brazilian STS patient. A population-based cohort study of 66,825 patients who underwent procedures related to STS treatment registered in the Brazilian public health system (Sistema Único de Saúde, SUS) databases. Median age was 57 years, 30% of them older than 65 years and 50.7% of the cohort was female. The majority, 50,383 patients (75.4%), was diagnosed between 2008 and 2015. Most prevalent anatomic sites were upper and lower limbs (12.6%) and the registry of sarcomas without a specific location comprehended 29.7% of the cohort. The majority of patients resided in the Northeast (40.2% of the patients). Surgery was the first treatment modality in 77.7% of the cases. For survival analysis, only patients with stage and histological grade information were included. The 1-, 5- and 10-year survival rate of the patients was, respectively, 75.4% (95% CI = 74.1-76.7%), 43.4% (95% CI = 41.5-45.5%) and 18.6% (95% CI = 14.8-23.3%).

Health-Related Quality of Life in Psoriatic Arthritis: Findings and Implications.

OBJECTIVES: To assess the quality of life (QOL) and its associated factors in patients with psoriatic arthritis (PsA) who would start treatment with biologic drugs at the Brazilian Unified Health System. METHODS: A cross-sectional study was performed at a single center pharmacy in Belo Horizonte, State of Minas Gerais, Brazil. EQ-5D was used to assess the patients' QOL. The functional status was assessed using the Health Assessment Questionnaire-Disability Index, whereas disease activity was evaluated through the Bath Ankylosing Spondylitis Disease Activity Index and the Clinical Disease Activity Index. Simple and multiple linear regression analyses were performed to assess the factors associated with QOL. RESULTS: A total of 212 patients with PsA were included, of which 185 (87.3%) reported having some pain/discomfort, and 148 (69.8%) presented some level of anxiety/depression. Patients with PsA had a mean QOL score of 0.651 (SD 0.12) with a significant reduction in female patients, concomitant use of nonsteroidal anti-inflammatory drugs, comorbidity, and worse clinical and functional status. Poor QOL was associated with worse functional status by the Health Assessment Questionnaire-Disability Index, disease activity by the Bath Ankylosing Spondylitis Disease Activity Index, and with diagnoses of osteoporosis, hypothyroidism, and depression. CONCLUSION: PsA and its associated comorbidities negatively affect the QOL, evidencing the need for a comprehensive and effective clinical approach.

Medication adherence and persistence of psoriatic arthritis patients treated with biological therapy in a specialty pharmacy in Brazil: a prospective observational study.

BACKGROUND: Pharmaceutical services in Brazil provide access, supply, and rational use of drugs for all population and an effort has been made to improve the quality of these services. Biological drugs are high-cost drugs supplied in Brazil that can inhibit disease progression and improve the quality of life of psoriatic arthritis (PsA) patients. However, some patients did not achieve therapeutic goals. OBJECTIVE: To evaluate the medication adherence and persistence of PsA patients treated with tumor necrosis factor inhibitors (anti-TNF) drugs and their associated factors. METHODS: A prospective observational study was performed at a single-specialty pharmacy in Belo Horizonte, Brazil. Medication adherence, persistence, and clinical outcomes were evaluated at 12 months of follow-up. Medication persistence was historically compared to overall PsA patients treated in Brazil. Associated factors were identified through log-binomial regression. RESULTS: One hundred ninety-seven PsA patients were included in the study, of whom 147 (74.6%) and 142 (72.1%) had medication adherence and persistence, respectively. Patients treated with infliximab presented the highest adherence (90.5%) and persistence rate (95.2%) in comparison to patients treated with other drugs, except for adalimumab versus infliximab for adherence outcome. All clinical measures significantly improved in patients with medication adherence and persistence. Medication persistence was higher for patients attended by specialty pharmacy than other PsA patients in Brazil. The associated factors to higher medication adherence were lower disease activity by BASDAI, being non-white race, and intravenous drug use. The associated factors to higher medication persistence were lower disease activity by Bath Ankylosing Spondylitis Activity Index (BASDAI), intravenous drug use, non-use of corticoids and non-steroidal anti-inflammatory drugs, and comorbidity. CONCLUSIONS: Patients with medication adherence and persistence had significant improvements in clinical measures, functionality, and quality of life. High medication adherence and persistence to biological therapy were observed and associated with lesser disease activity at baseline. Also, medication persistence to PsA patients attended in specialty pharmacy was higher than the overall PsA population in Brazil, which indicates the importance of pharmaceutical services to provide health care and promote the effectiveness and safety of biological therapies.

Access to medicines in the Brazilian Unified Health System's primary health care: assessment of a public policy.

In 2008, the Programa Rede Farmácia de Minas (RFM, literally translated: 'Minas Gerais Pharmacy Network' program) was created as a strategy to expand access to medicines. Aim: Measure access to medicines in public pharmacies through comparison between municipalities that joined or not the RFM. Materials & methods: Cross-sectional, evaluative study, gathering information from a representative sample of the municipalities in Minas Gerais between July 2014 and May 2015. The Poisson regression results were obtained by calculating the prevalence ratios. Results: Adequate access to medicines in Minas Gerais was 69.9%, being 75.8% in municipalities with and 69.2% without the RFM. The municipalities with the RFM showed statistically higher percentages in the Availability, Adequacy/Accommodation, and Acceptability dimensions. Conclusion: RFM appears an efficient strategy for promoting access to medicines.

Effectiveness and safety of anti-TNF therapy for ankylosing spondylitis: a real-world study.

Aim: To evaluate the effectiveness and safety of anti-TNF drugs for ankylosing spondylitis. Materials & methods: A prospective cohort study was performed at a pharmacy in the Brazilian Public Health System. Effectiveness by Bath Ankylosing Spondylitis Disease Activity Index, functionality by Health Assessment Questionnaire Disability Index, quality of life by European Quality of Life Five-Dimensions and safety was assessed at 6 and 12 months of follow-up. Results: About 160 patients started the treatment with adalimumab, etanercept or infliximab. There was a statistically significant improvement in disease activity, functionality and quality of life at 6 and 12 months (p < 0.05). Conclusion: This real-world study has shown that anti-TNF drugs are effective and well tolerated for ankylosing spondylitis patients.

Strategies to improve the availability of medicines in primary health care in Brazil: findings and implications.

Aim: Access to essential medicines is a key component of managing patients in ambulatory care. In 2008, the State of Minas Gerais, Brazil, created the Pharmacy Network of Minas (Rede Farmácia de Minas [RFM]) program to improve access to medicines, increasing availability and restructuring the infrastructures. The aim was to assess the current situation, comparing municipalities with and without RFM. Materials & methods: Descriptive survey study, data collected from 2014 July to May 2015. Availability was verified by stock levels. Results: The drug availability index was 61.0%, higher in municipalities with RFM. Most physicians considered the pharmaceutical services as good/very good. The main reasons for medicines shortage were 'financial transference problems', 'insufficient financial resources' and 'budget'. Conclusion: Strategies, such as the RFM can promote improvements in medicine availability.

The Budget Impact of Monoclonal Antibodies Used to Treat Metastatic Colorectal Cancer in Minas Gerais, Brazil.

INTRODUCTION: Biological medicines have increased the cost of cancer treatments, which also raises concerns about sustainability. In Brazil, three monoclonal antibodies (mAbs)-bevacizumab, cetuximab, and panitumumab-are indicated for the treatment of metastatic colorectal cancer (mCRC) but not currently funded by the Unified Health System (SUS). However, successful litigation has led to funding in some cases. OBJECTIVE: Our objective was to evaluate the budgetary impact of including the mAbs bevacizumab, cetuximab, and panitumumab in standard chemotherapy for the treatment of mCRC within the SUS of Minas Gerais (MG), Brazil. METHOD: A budget impact analysis of incorporating mAbs as first-line treatment of mCRC in MG was explored. The perspective taken was that of the Brazilian SUS, and a 5-year time horizon was applied. Data were collected from lawsuits undertaken between January 2009 and December 2016, and the model was populated with data from national databases and published sources. Costs are expressed in $US. RESULTS: In total, 351 lawsuits resulted in funding for first-line treatment with mAbs for mCRC. The three alternative scenarios analyzed resulted in cost increases of 348-395% compared with the reference scenario. The use of panitumumab had a budgetary impact of $US103,360,980 compared with the reference scenario over a 5-year time horizon, and bevacizumab and cetuximab had budgetary impacts of $US111,334,890 and 113,772,870, respectively. The use of the anti-epidermal growth factor receptor (EGFR) mAbs (cetuximab and panitumumab) is restricted to the approximately 41% of patients with KRAS mutations, so the best cost alternative for incorporation would be the combination of panitumumab and bevacizumab, with a cost of approximately $US106 million. CONCLUSION: These results highlight the appreciable costs for incorporating bevacizumab, cetuximab, and panitumumab into the SUS. Appreciable discounts are likely to be necessary before incorporation of these mAbs is approved.

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.

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.

Cost Analysis of Cancer in Brazil: A Population-Based Study of Patients Treated by Public Health System From 2001-2015.

OBJECTIVES: The aim of this study was to evaluate the federal government expenditures with oncological care, for the most incident cancer types among the Brazilian population, using registries of all patients treated by the Brazilian National Health Service (SUS) between 2001 and 2015. We adopted the formal healthcare sector perspective in this study, with the costs per patient estimated by the reimbursement price paid by the Ministry of Health to service providers. METHODS: The costs were adjusted by the follow-up time for each patient. We performed multivariate regression analysis using ordinary least squares. We analyzed 952 960 patients aged ≥19 years who underwent cancer treatment, between 2001 and 2015, for breast, prostate, colorectal, cervix, lung, and stomach cancers. RESULTS: The annual mean costs per patient (in USD purchasing power parity) was $9572.30, varying from $5782.10 for breast cancer to $16 656 for cervical cancer. Several variables predicted higher costs of cancer treatment, namely: to be male (+14%), with younger age ranges at treatment initiation, resident in the Northeast region (+26%), treated for colorectal cancer (+482%), with treatment initiation from 2010 to 2014, tumor stages III and IV (III: +182%; IV: +165%), hospitalization for other reasons besides the cancer treatment, and suffering from some a comorbidity. CONCLUSIONS: Given the forthcoming Brazilian demographic changes, which strongly suggest that the economic burden of cancer is about to increase in the near future, our estimates provide relevant information to produce useful projections about future cancer-related costs.

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.

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.

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.