Comparative effectiveness of adalimumab and etanercept for rheumatoid arthritis in the Brazilian Public Health System

Aim: Biological disease-modifying antirheumatic drugs (bDMARDs) are used to treat rheumatoid arthritis (RA) with adalimumab and etanercept the most used bDMARDs in Brazil. This open prospective cohort study evaluated their effectiveness and safety among RA patients in the Brazilian Public Health System given their costs. Methods: The Clinical Disease Activity Index was primarily used to assess their effectiveness after 6 and 12 months of follow-up. The Health Assessment Questionnaire and EuroQol-5D were also used. Results: A total of 266 RA patients started treatment with adalimumab or etanercept. Adalimumab was the most widely used bDMARD (70%). In total, 46% achieved remission or low-disease activity at 12 months with no difference in effectiveness between them (p = 0.306). bDMARDs were more effective in patients who had better functionality at treatment onset and had spent longer in education. Conclusion: This real-world study demonstrated that adalimumab and etanercept are equal alternatives for RA treatment and both were well tolerated

Profile of patients with rheumatic diseases undergoing treatment with anti-TNF agents in the Brazilian Public Health System (SUS), Belo Horizonte - MG

The aim of this study was to describe the baseline demographic and clinical characteristics as well as the functional status of a prospective cohort of patients with rheumatic diseases assisted by the Brazilian Public Health System (SUS). Data for 302 patients receiving tumor necrosis factor α inhibitors (anti-TNF agents) was collected through a standard form. Among patients, 229 (75.8%) were female and 155 (51.3%) were Caucasian; the mean age was 50.3 ± 12.8 years, and the mean disease duration was 9.9 ± 8.7 years. Among them 214 patients (70.9%) received adalimumab, 72 (23.8%) etanercept, and 16 (5.3%) infliximab. Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) was 1.37 ± 0.67 for all participants. Poor functional response was associated with female gender, married patients and with a score of &lt; 0.6 on the EuroQoL-5 dimensions (EQ-5D). Significant correlation was found between the HAQ-DI values, disease activity and quality of life (QOL). The results obtained in this study contribute to a better understanding of the clinical and demographic characteristics of patients with rheumatic diseases at the beginning of anti-TNF-agent treatment by SUS. Furthermore, our findings are consistent with another Brazilian and foreign cross-sectional investigations. This knowledge can be of great importance for further studies evaluating the effectiveness of biological agents, as well as, to contribute to improve the well-being of the patients with rheumatic diseases.O objetivo do estudo foi descrever as características demográficas e clínicas iniciais, bem como o estado funcional de uma coorte de pacientes com doenças reumáticas tratados pelo Sistema Único de Saúde (SUS). Dados de 302 pacientes em uso de inibidores do fator de necrose tumoral (agentes anti-TNF) foram coletados por formulário padronizado. Desses, 229 (75.8%) eram mulheres e 155 (51.3%) eram brancos; a idade média foi 50,3 ± 12,8 anos, e a duração média da doença foi de 9,9 ± 8,7 anos. Entre os pacientes 214 (70,9%) usaram adalimumabe, 72 (23,8%) etanercepte e 16 (5,3%) infliximabe. A média do Health Assessment Questionnaire-Disability Index (HAQ-DI) foi 1,37 ± 0,67 para a população total. Pior resposta funcional estava associada com mulheres, pacientes casados e com um valor de EuroQoL-5 dimensions (EQ-5D) < 0.6. Correlação significativa foi obtida entre os valores de HAQ-DI, atividade das doenças e qualidade de vida. Os resultados obtidos no estudo contribuem para o melhor entendimento das características clínicas e demográficas de pacientes com doenças reumáticas iniciando a terapia com agentes anti-TNF pelo SUS. Além disso, nossos achados são consistentes com resultados obtidos em outros estudos transversais nacionais e estrangeiros. Este conhecimento pode ser de grande importância para estudos futuros que avaliem a eficácia de agentes biológicos, assim como, para contribuir para a melhoria do bem-estar das pessoas com doenças reumáticas

A systematic review and meta-analysis of enzyme replacement therapy in late-onset Pompe Disease

Pompe disease (PD) is a glycogen storage disorder caused by deficient activity of acid alpha-glucosidase (GAA). We sought to review the latest available evidence on the safety and efficacy of recombinant human GAA enzyme replacement therapy (ERT) for late-onset PD (LOPD). Methods: We systematically searched the MEDLINE (via PubMed), Embase, and Cochrane databases for prospective clinical studies evaluating ERT for LOPD on pre-specified outcomes. A meta-analysis was also performed. Results: Of 1601 articles identified, 22 were included. Studies were heterogeneous and with very low certainty of evidence for most outcomes. The following outcomes showed improvements associated with GAA ERT, over a mean follow-up of 32.5 months: distance walked in the 6-min walking test (6MWT) (mean change 35.7 m (95% confidence interval [CI] 7.78, 63.75)), physical domain of the SF-36 quality of life (QOL) questionnaire (mean change 1.96 (95% CI 0.33, 3.59)), and time on ventilation (TOV) (mean change -2.64 h (95% CI -5.28, 0.00)). There were no differences between the pre- and post-ERT period for functional vital capacity (FVC), Walton and Gardner-Medwin Scale score, upper-limb strength, or total SF-36 QOL score. Adverse events (AEs) after ERT were mild in most cases. Conclusion: Considering the limitations imposed by the rarity of PD, our data suggest that GAA ERT improves 6MWT, physical QOL, and TOV in LOPD patients. ERT was safe in the studied population. PROSPERO register: 135102

Forecasting models for leprosy cases: a scoping review protocol

Introduction Leprosy is a neglected tropical disease caused by Mycobacterium leprae that mainly affects the skin, the peripheral nerves, the mucosa of the upper respiratory tract and the eyes. Mathematical models and statistical methodologies could play an important role in decision-making and help maintain the gains in elimination programmes. Various models for predicting leprosy cases have been reported in the literature, but they have different settings and distinct approaches to predicting the cases. This study describes the protocol for a scoping review to identify and synthesise information from studies using models to forecast leprosy cases.Methods and analysis A scoping review methodology will be applied following the Joanna Briggs Institute methodology for scoping reviews and will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews. We will perform a systematic search from when each database started until April 2022 and we will include the following electronic databases: MEDLINE via PubMed, Embase, Cochrane Library and Latin American and Caribbean Health Science Literature Database. Data will be extracted and recorded on a calibrated predefined data form and will be presented in a tabular form accompanied by a descriptive summary. The Prediction Model Study Risk of Bias Assessment Tool (PROBAST) will be used.Ethics and dissemination No ethical approval is required for this study. This scoping review will identify and map the methodological and other characteristics of modelling studies predicting leprosy cases. We hope that the review will contribute to scientific knowledge in this area and act as a basis for researchers designing and conducting leprosy models. This information can also be used to enhance national surveillance systems and to target specific policies. The protocol and consequent publications of this scoping review will be disseminated through peer-reviewed publications and policy briefs.Systematic review registration This scoping review was registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/W9375)

Pharmacotherapy applied to substance use disorder (alcohol and other drugs) in public health systems

Scoping revie

Perfil das ações judiciais em assistência à saúde com bloqueio de verbas públicas no Estado de Santa Catarina

Objetivo: analisar o perfil situacional dos bloqueios de valores decorrentes do descumprimento de decisões judiciais em assistência à saúde, no Estado de Santa Catarina. Métodos: foram considerados os processos com determinação de bloqueio nas contas do Estado de Santa Catarina, nos meses de dezembro de 2015 e dezembro de 2016, em que os autores requereram medicamentos, insumos e nutrição. Resultados: a maioria das ações são ajuizadas individualmente e por escritórios de advocacia particulares. Medicamentos configuraram como o objeto mais solicitado, prescritos em sua maioria pelo nome comercial e não padronizados em listas oficiais em mais de 70% dos casos. Em 2015, o gasto mensal foi de R$135.549,39, e, caso o Estado tivesse realizado a aquisição, o gasto mensal seria de R$ 82.016,29. Em dezembro de 2016, o gasto com bloqueio foi de R$833.634,88, enquanto por meio de compra administrativa seria de R$ 447.357,68. Observou-se um crescimento de 858,82% dos gastos com bloqueios, do ano de 2015 para 2016. Conclusões: os resultados obtidos podem contribuir para o melhor planejamento do cumprimento das decisões judiciais em saúde, evitando que não onerem ainda mais os cofres públicos e prejudiquem o orçamento da saúde pública

Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis

Abstract What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD − 0.07, 95% CrIs − 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD − 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis

7-Chloroquinolinotriazoles : synthesis by the azide-alkyne cycloaddition click chemistry, antimalarial activity, cytotoxicity and SAR studies.

Twenty-seven 7-chloroquinolinotriazole derivatives with different substituents in the triazole moiety were synthesized via copper-catalyzed cycloaddition (CuAAC) click chemistry between 4-azido-7- chloroquinoline and several alkynes. All the synthetic compounds were evaluated for their in vitro activity against Plasmodium falciparum (W2) and cytotoxicity to Hep G2A16 cells. All the products disclosed low cytotoxicity (CC50 > 100 mM) and five of them have shown moderate antimalarial activity (IC50 from 9.6 to 40.9 mM). As chloroquine analogs it was expected that these compounds might inhibit the heme polymerization and SAR studies were performed aiming to explain their antimalarial profile. New structural variations can be designed on the basis of the results obtained