The aim of this study was to evaluate interruption of treatment with biological drugs and tofacitinib due to adverse events in patients with rheumatoid arthritis. A systematic review was performed in the electronic databases MEDLINE, Cochrane, Scopus, CRD, IPA, Lilacs and Scielo. Case reports addressing interruption of treatment due to any adverse event related to abatacept (ABA), adalimumab (ADA), anakinra (ANA), certolizumab pegol (CER), etanercept (ETA), golimumab (GOL), infliximab (IFX), rituximab (RTX), secukinumab (SEC), tocilizumab (TCZ), tofacitinib (TOF) or ustekinumab (UST) in rheumatoid arthritis patients were evaluated. Baseline data, patient profile, previous and current treatments, cause of discontinuation and information on reintroduction of treatment were extracted from the case reports. One hundred and fifty-four studies (154 patients) reported 162 discontinuations of rheumatoid arthritis treatment due to adverse events (ETA = 57; IFX = 46; ADA = 32; TCZ = 13; RTX = 5; ANA = 3; GOL = 2; ABA = 2; TOF = 1; CER = 1; SEC = 0 and UST = 0). The mean age of patients was 56 (± 12.1) years and 82% were female. Seventy-four adverse events were confirmed (related to used drug), and 138 were observed in patients using anti-TNF. The most common adverse events were infections (21%), skin disease (15%), autoimmune disease (13%) and hematological disorders (9%). Case reports are important in the detection of rare adverse events and should be considered in the choice of appropriate therapy for patients.

Resumo: Os objetivos foram efetuar a análise do impacto orçamentário para a incorporação de segunda linha terapêutica com terapia antiangiogênica de aplicação intravítrea, para tratamento de edema macular diabético, no âmbito do Sistema Único de Saúde (SUS) em Minas Gerais, Brasil, discutindo sua viabilidade à luz do orçamento do estado. A análise do impacto orçamentário com método determinístico, segundo diretriz do Ministério da Saúde. Foram incluídos os pacientes com provável falha ao tratamento de primeira linha, num horizonte temporal de 5 anos para todas as tecnologias avaliadas. Incluíram-se na análise os medicamentos bevacizumabe (uso off-label), ranibizumabe e aflibercepte. As populações foram calculadas tanto por demanda aferida quanto por estimativa epidemiológica. Como análises de sensibilidade efetuaram-se: cenário com difusão de tecnologia mais lenta; cenário com a entrada de bevacizumabe e ranibizumabe biossimilares no mercado; cenário com a desconsideração da inflação no período. O impacto orçamentário incremental, de acordo com as estimativas de demanda aferida e epidemiológica, respectivamente, foi de R$ 69.493.906,95-R$ 473.226.278,78 para bevacizumabe; R$ 349.319.965,60-R$ 2.378.732.103,09 para ranibizumabe e R$543.867.485,47-R$ 3.703.524.490,16 para aflibercepte. Bevacizumabe foi a alternativa financeiramente mais viável em todos os cenários das estimativas e análises de sensibilidade. Estimou-se incremento próximo a 3%, comparando com o orçamento de 2016 (demanda aferida). Avalia-se que a incorporação é viável dentro do SUS em Minas Gerais, mas sujeita às prioridades da gestão. A discrepância de preços entre produtos de eficácia semelhante é intrigante e tema fértil para estudos futuros.

No abstract

The discontinuation rates reported for non-anti-TNF drugs varied relative to the study design in which they were investigated. Regulatory agencies, price-setting entities, and evidence-gathering researchers should consider the effect of the real-life environment in their decisions and conclusions.

A ampliação da variedade de diretrizes clínicas em oncologia é perceptível em todo o mundo, o que salienta a necessidade de garantir a qualidade destes documentos. Assim, o objetivo do estudo foi avaliar a qualidade de diretrizes nacionais de tratamentos dos cânceres de mama, próstata e de cólon e reto. Foram selecionadas 12 diretrizes brasileiras publicadas por quatro grupos elaboradores distintos (Ministério da Saúde, sistema suplementar de saúde e de sociedades e associações médicas), e aplicado o instrumento AGREE II. Em todas as diretrizes avaliadas foram identificadas fragilidades importantes em mais de um Domínio, com destaque para os baixos valores para “aplicabilidade” e “independência editorial”. Os padrões observados por Domínios apresentam-se mais relacionados com o grupo elaborador do que com as condições clínicas tratadas. Menores escores no “rigor do desenvolvimento” e “independência editorial” foram obtidos por grupos elaboradores não governamentais, inclusive com ausência ou falta de transparência nas informações. Mesmo que a “clareza da apresentação” das diretrizes do Ministério da Saúde tenha sido relativamente inferior, na “aplicabilidade” todas apresentaram limitações expressivas. Consequentemente, na avaliação global nenhuma das diretrizes foi recomendada sem modificações, sendo quatro delas não recomendadas. Por fim, é necessário qualificar as recomendações no que tange as evidências que as fundamentam (“rigor metodológico”), assim como dispor de forma compreensível e exequível as condutas a serem adotadas (“aplicabilidade”) e mitigar interesses conflitantes, para que seja ofertado o melhor cuidado aos pacientes oncológicos no país.

OBJECTIVE To identify demographic and clinical characteristics of adult patients hospitalized in the Brazilian Unified Health System (SUS) due to viral pneumonia and investigate the association between some comorbidities and death during hospitalization. METHODS This retrospective cohort study was conducted with secondary data of adults admitted to SUS due to viral pneumonia between 2002 and 2015. Patient profile was characterized based on demographic and clinical variables. The association between the ten Elixhauser comorbidities and in-hospital death was investigated using Poisson regression models with robust standard errors. Results were quantified as incidence rate ratio (IRR) with 95% confidence intervals (CI), and we built five models using successive inclusion of variables blocks. RESULTS Hospital admissions for viral pneumonias decreased throughout the study period, and it was observed that 5.8% of hospitalized patients had an in-hospital death. We observed significant differences in demographic and clinical characteristics by comparing individuals who died during hospitalization with those who did not, with the occurrence of one or more comorbidities being more expressive among patients who died. Although not considered risk factors for in-hospital death, chronic pulmonary disease and congestive heart failure were the most common comorbidities. Conversely, IRR for in-hospital death increased with other neurological disorders, diabetes, cancer, obesity, and especially with HIV/AIDS. CONCLUSIONS Individuals presenting with pulmonary and cardiovascular diseases require proper attention during hospitalization, as well as those with other neurological diseases, diabetes, cancer, obesity, and especially HIV/AIDS. Understanding the influence of chronic diseases on viral infections may support the healthcare system in achieving better outcomes.

A837was tolerability related to the number of withdrawals patients in each study, due to the presence of adverse events or treatment failure. The analyses were performed using software Addis (v.1.16.5) and RevMan (5.1). Results: A total of 979 documents were initially identified and 11 of them met the selection criteria to meta-analysis. No significant differences were observed between the number of withdrawals patients due adverse events in any meta-analysis of control versus intervention. The odds ratio ranged from 0.68 (CI 032-1.45) to placebo versus asenapine, 1.37 (CI 0.29-1.33) to placebo versus iloperidone and 0,71 (CI 0,36-1,41) to placebo versus lurasidone. However, all drugs were superior to their respective controls for the outcome of number of withdrawals by treatment failure, with odds ratio between 1.70 (CI 1.21-2.39) and 2.36 (CI 1.36-4.07). These results suggest that there is a higher effectiveness among patients for the treatment intervention that should be evaluated through clinical responses. Heterogeneity between studies (evaluated by I2 values) were low or moderate, not superior than 39,5% in any meta-analysis. ConClusions: Information and knowledge reunion and confrontation on the tolerability profile of a particular drug allows safer decisions over the therapeutic approach, focused on patient's interest which directly reflects on treatment follow-through and therapy effectiveness. In this study, we report evidence on asenapine, iloperidone and lurasidone greater tolerability profile compared to placebo in schizophrenia treatment.

Objectives: The PARP inhibitors (PARPi) niraparib, olaparib, and rucaparib are approved for maintenance treatment of platinum sensitive recurrent ovarian cancer (PSROC). Modifications to the recommended doses may occur due to adverse reactions, co-morbidities, and the use of concomitant medication. The objective of this study was to determine the real-world average doses of PARPi therapies used in the PSROC maintenance setting. Methods: This retrospective, real-world study utilized Flatiron Health EHR-derived de-identified oncology database representing over 2.2 million US patients nationwide. The dataset comprised patients diagnosed with ovarian cancer from 1 January 2011 to 31 August 2019 who received PARPi maintenance therapy in the second or later line after completing a platinum-based regimen. Results: Recommended daily doses for niraparib, olaparib, and rucaparib are 300 mg, 600 mg, and 1200 mg respectively. These represent "standard" recommended doses. Results of this analysis are reported for 2L, 2L and beyond (2L+), and 3L and beyond (3L+). 142 patients were included, 75 received niraparib, 38 received olaparib, and 29 received rucaparib. Average daily starting doses were: niraparib -253 mg (2L), 248 mg (2L+), 242 mg (3L+); olaparib -524 mg (2L), 514 mg (2L+), 492 mg (3L+); and rucaparib -1171 mg (2L), 1133 mg (2L+), 1092 mg (3L+). The average daily doses over the course of treatment were: niraparib -218 mg (2L), 204 mg (2L+), 186 mg (3L+); olaparib -536 mg (2L), 513 mg (2L+), 460 mg (3L+); and rucaparib -912 mg (2L), 973 mg (2L+), 1039 mg (3L+). Conclusions: The data presented show the real world average starting dose for the 3 PARPi and the average dose during maintenance treatment. For each drug, the average dose during maintenance treatment is lower than the average starting dose.