Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis.

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have been highly effective and are comparable in reducing RA symptoms, slowing disease progression, and improving physical function; however, concerns have been raised about the risks of several potential adverse effects. Thus, this study aimed to assess the safety of biological therapy in patients with rheumatoid arthritis in observational studies using administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science were searched from inception to 21 October 2021. The analysis was divided into five groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus csDMARDs; bDMARDs versus csDMARDs; abatacept versus bDMARDs; and TNFi versus Janus kinase inhibitors (JAKi). The adverse events were cancer, cardiovascular events, infection, herpes zoster, tuberculosis, and death. The methodological quality of the studies was assessed by the Newcastle-Ottawa Scale. A random-effects model estimated risk ratios with 95% confidence intervals. Results: Thirty-one studies were eligible for inclusion in the present systematic review, published from 2014 to 2021. A total of 1,039,398 RA patients were assessed. The 31 studies evaluated eleven different biological drugs. No significant differences were found regarding safety between TNFi versus non-TNFi (RR 1.08; 95% CI 0.92-1.28; p < 0.01; I2 = 93.0%), TNFi versus csDMARDs (RR 0.91; 95% CI 0.75-1.10; p < 0.01; I2 = 87.0%), bDMARDs versus csDMARDs (RR 0.99; 95% CI 0.82-1.20; p < 0.01; I2 = 93.0%), abatacept versus bDMARDs (RR 0.80; 95% CI 0.54-1.18; p < 0.01; I2 = 90.0%), and TNFi versus JAKi (RR 3.54; 95% CI 0.30-42.09; p = 0.01; I2 = 81.0%). In the subgroup analysis, among studies comparing abatacept to TNFi, a lower risk of cardiovascular events was associated with abatacept (RR 0.37; 95% CI 0.24-0.55). Conclusion: Our results do not suggest an increased risk of adverse events associated with biological therapy in treating RA patients, indicating a lower risk of cardiovascular events with abatacept than TNFi. However, these findings must be interpreted with caution given the limitations of this study and the low/very low certainty of the evidence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42020190838].

Software de programação dos medicamentos tuberculostáticos e Hansenostáticos

A Tuberculose e a Hanseníase são doenças que ocorrem em grande parte da população brasileira, independente da idade e do sexo, mas com maior prevalência nas classes sociais menos favorecidas, o que torna essas doenças de interesse prioritário para o Ministério da Saúde, que considerou os programas nacionais como estratégicos, desenvolvendo várias ações para o seu controle e erradicação. Como a garantia do acesso ao medicamento é a principal ação para o controle desses agravos, torna-se necessária a elaboração da programação e distribuição dos medicamentos, evitando o desabastecimento e perdas, como ocorrido na sistemática adotada nas programações até o ano 2000. Neste sentido, tornou-se essencial elaborar um software de programação de medicamentos tuberculostáticos e hansenostáticos. No final de 2000, a Secretaria de Políticas de Saúde, por meio da Gerência Técnica de Assistência Farmacêutica – GTAF, constituiu um grupo de trabalho, composto por técnicos da GTAF e da Área Técnica de Pneumologia e Dermatologia Sanitária do MS e consultores de alguns estados, com a finalidade de elaborar o instrumento. O software foi elaborado baseado em critérios epidemiológicos e técnicos e implantado nas 27 Unidades Federadas, as quais utilizaram o instrumento nas programações de 2002 e 2003 e desenvolveram um plano de trabalho para a implantação em todos os seus municípios. A utilização do software na programação promoveu: diminuição da aquisição da maioria dos medicamentos por parte do MS, sem gerar desabastecimento; redução significativa das perdas; aproveitamento dos quantitativos excedentes da programação em curso; adequação da distribuição estadual de medicamentos de acordo com os esquemas terapêuticos recomendados pelo MS; uniformização do esquema terapêutico utilizado pelas Coordenações Estaduais, entre outros. Na programação dos medicamentos hansenostáticos de 2002, em relação a 2001, a utilização do software propiciou uma diminuição da aquisição em média de (vinte e um porcento) da maioria dos medicamentos, em 2003, em relação a 2002, reduziu em média (trinta e oito porcento). Na programação dos medicamentos tuberculostáticos de 2002, em relação a 2001, reduziu a aquisição em média (quarenta e oito porcento) , sendo que para a Isoniazida 100mg com., chegou a (noventa e quatro porcento)