Uso de anti-tnf na artrite reumatóide e o aparecimento de autoanticorpos e doença auto-imune.

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clínica Médica

Ensaio clínico randomizado para comparação da administração matutina versus noturna da levotiroxina no controle de hipotireoidismo em idosos

O hipotireoidismo primário resulta da disfunção da glândula tireoide, e sua principal causa é a Tireoidite de Hashimoto. A prevalência varia conforme a população analisada; é maior no sexo feminino e aumenta em maiores faixas de idade. A levotiroxina em monoterapia é utilizada para reposição hormonal e o valor de TSH sérico (Thyroid-Stimulating Hormone) alvo é maior em populações idosas. Questões, como: o momento da administração (se em jejum ou no período pós-prandial), uso concomitante a outras medicações e a presença de comorbidades podem interferir na farmacocinética da levotiroxina, comprometendo a efetividade do tratamento. Os ensaios clínicos sobre a administração posológica alternativa da levotiroxina avaliaram sobretudo adultos jovens; nesse contexto a tomada noturna demonstrou resultados superiores ou semelhantes em relação ao uso diurno. Diante do exposto, o objetivo do presente projeto foi testar pragmaticamente a efetividade da levotiroxina no controle do hipotireoidismo em idosos, comparando a administração noturna à diurna, através de um ensaio clínico randomizado com crossover. A amostra foi composta de 201 indivíduos acima de 60 anos, com multimorbidades e polifarmácia, porém funcionalmente independentes; em tratamento com levotiroxina de longa data e em sua maioria com hipotireoidismo controlado. Os níveis de TSH permaneceram dentro dos valores de normalidade, independente da estratégia da tomada da levotiroxina (60 minutos antes do café da manhã ou 60 minutos após a última refeição). Portanto, a ingestão noturna da levotiroxina pode ser considerada no tratamento do hipotireoidismo também no grupo dos idosos

Evaluation of evening versus morning levothyroxine intake in elderly (MONIALE)

Background: The aging population is associated with increased multimorbidity and polypharmacy. Older adults are at a higher risk of adverse events and reduced therapeutic response. This phenomenon is partially explained by drug interactions and treatment adherence. Most randomized clinical trials have found no significant differences between morning and evening levothyroxine (LT4) administration in young adults, but there is little evidence regarding alternative LT4 regimens in older populations. Thus, the MONIALE trial aims to test an alternative schedule for LT4 administration in older adults. Methods/design: This randomized crossover clinical trial will include participants aged 60 years or older with primary hypothyroidism. The trial groups will consist of morning LT4 intake (60 min before breakfast) or evening LT4 intake (60 min after supper). The primary outcome will be variation in serum thyrotropin (TSH) levels after 24 weeks of the LT4 protocol. The secondary outcomes will be the prevalence of drugs that potentially interact with LT4 and hypothyroidism control according to interaction status. The sample size was calculated to detect a minimum mean difference of 1 mUI/L in serum TSH level between the groups with 80% power and a 5% probability of type I error, resulting in 91 patients per group. The project was approved by the Hospital de Clínicas de Porto Alegre Ethics Committee. Discussion: Considering the aging population, the increased prevalence of multimorbidity and polypharmacy, as well as potential drug interactions and treatment adherence difficulties, an alternative LT4 protocol could be useful for hypothyroidism treatment in the elderly. Prior studies comparing alternative LT4 administration protocols have mainly included young adult populations and have not addressed potential drug interactions

Legionella pneumonia after infliximab in a patient with Rheumatoid Arthritis

AbstractThe antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients

Evaluation of bedtime vs. morning levothyroxine intake to control hypothyroidism in older patients : a pragmatic crossover randomized clinical trial

Introduction: Drug scheduling in older adults can be a challenge, especially considering polypharmacy, physical dependency, and possible drug interactions. Properly testing alternative treatment regimens could therefore help to overcome treatment barriers. Hypothyroidism is a prevalent condition in older adults, however, studies evaluating Lthyroxine treatment effectiveness in this specific age group are still lacking. Most studies testing an evening administration of levothyroxine were mainly composed of younger adults. Therefore, this trial is aimed to assess if evening levothyroxine (LT4) administration can effectively control hypothyroidism in older patients. Materials and Methods: A randomized crossover clinical trial was conducted between June 2018 and March 2020 at the Hospital de Clínicas de Porto Alegre, a teaching hospital in Brazil, to compare the efficacy of morning and evening administration of LT4 for hypothyroidism control in older patients. The study protocol is published elsewhere. A total of 201 participants, ≥60 years old, with primary hypothyroidism treated with LT4 for at least 6 months and on stable doses for at least 3 months were included. Participants were randomly assigned to a starting group of morning LT4 intake (60min before breakfast) or bedtime LT4 intake (60min after the last meal). After ≥12 weeks of follow-up, a crossover between strategies was performed. The primary outcome was the change in serum thyrotropin (Thyroid-Stimulating Hormone; TSH) levels after 12 weeks of each LT4 administration regimen. Results: A total of 201 participants with mean age of 72.4 ± 7.2 years were included, out of which 84.1% were women; baseline characteristics and frequency of controlled hypothyroidism were similar between groups. Mean baseline TSH was 3.43 ± 0.25 mUI/L. In total, 118 participants attended three meetings, allowing 135 comparisons by crossover analytic strategy. Mean TSH levels after follow-up were 2.95 ± 2.86 in the morning group and 3.64 ± 2.86 in the bedtime group, p = 0.107. Discussion: Thyroid-Stimulating Hormone levels and frequency of controlled hypothyroidism were similar during the follow-up period regardless of the treatment regimen (morning or bedtime)

Ensaio clínico randomizado para comparação da administração matutina versus noturna da levotiroxina no controle de hipotireoidismo em idosos

O hipotireoidismo primário resulta da disfunção da glândula tireoide, e sua principal causa é a Tireoidite de Hashimoto. A prevalência varia conforme a população analisada; é maior no sexo feminino e aumenta em maiores faixas de idade. A levotiroxina em monoterapia é utilizada para reposição hormonal e o valor de TSH sérico (Thyroid-Stimulating Hormone) alvo é maior em populações idosas. Questões, como: o momento da administração (se em jejum ou no período pós-prandial), uso concomitante a outras medicações e a presença de comorbidades podem interferir na farmacocinética da levotiroxina, comprometendo a efetividade do tratamento. Os ensaios clínicos sobre a administração posológica alternativa da levotiroxina avaliaram sobretudo adultos jovens; nesse contexto a tomada noturna demonstrou resultados superiores ou semelhantes em relação ao uso diurno. Diante do exposto, o objetivo do presente projeto foi testar pragmaticamente a efetividade da levotiroxina no controle do hipotireoidismo em idosos, comparando a administração noturna à diurna, através de um ensaio clínico randomizado com crossover. A amostra foi composta de 201 indivíduos acima de 60 anos, com multimorbidades e polifarmácia, porém funcionalmente independentes; em tratamento com levotiroxina de longa data e em sua maioria com hipotireoidismo controlado. Os níveis de TSH permaneceram dentro dos valores de normalidade, independente da estratégia da tomada da levotiroxina (60 minutos antes do café da manhã ou 60 minutos após a última refeição). Portanto, a ingestão noturna da levotiroxina pode ser considerada no tratamento do hipotireoidismo também no grupo dos idosos