Safety of Janus Kinase Inhibitors in Patients With Inflammatory Bowel Diseases or Other Immune-mediated Diseases: A Systematic Review and Meta-Analysis.

BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis. METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990, through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events. RESULTS: We identified 973 studies; of these, 82 were included in the final analysis, comprising 66,159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared with patients given placebo or active comparator (relative risk 0.72; 95% confidence interval 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% confidence interval 1.04-2.37). CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.

Postoperative mortality in inflammatory bowel disease patients / Mortalidade em portadores de doença inflamatória intestinal submetidos a tratamento cirúrgico

ABSTRACT Introduction: Since the 1960s, mortality in Crohn's disease and Ulcerative Colitis patients had a significant decrease due to advances in medical and surgical therapy. An important proportion of these patients are submitted to surgical procedures during their disease course, with postoperative mortality between 4 and 10%. Methods: 157 inflammatory bowel disease patients submitted to surgical therapy were retrospectively identified and allocated in 2 groups (Crohn's and colitis). Deaths were individually discriminated in detail. Results: 281 surgical procedures were performed. In the colitis group, 43 operations were performed in 24 patients; in the abdominal Crohn's subgroup, 127 procedures in 90 patients and in the perineal Crohn's subgroup, 115 in 64 patients, respectively. Nine postoperative deaths were observed (3 in the colitis and 6 in the Crohn's groups). Overall postoperative mortality was 5.7% (4.5% for Crohn's; 6.6% in abdominal Crohn's and 12.5% for Colitis). Most of deaths were related to emergency procedures and previous use of corticosteroids. The cause of death in all patients was sepsis. Conclusions: Overall postoperative mortality in inflammatory bowel disease was 5.7%, and it was attributed to the severity of the cases referred.

RESUMO Introdução: A partir da década de 60, a mortalidade dos portadores de doença de Crohn (DC) e a Retocolite Ulcerativa Inespecífica (RCUI) teve declínio devido a novas terapêuticas clínicas e cirúrgicas. Importante proporção destes pacientes é submetida a procedimentos cirúrgicos no decorrer das suas vidas, com taxas de mortalidade variando entre 4 e 10%. Método: Foram identificados retrospectivamente 157 pacientes portadores de doenças inflamatórias intestinais (DII), submetidos a operações abdominais ou perineais, divididos em dois grupos (DC e RCUI). Os casos de óbitos foram discriminados e avaliados individualmente, de forma descritiva. Resultados: 281 operações foram realizadas. No grupo RCUI foram realizadas 43 operações em 24 pacientes, no subgrupo DC abdominal, 127 operações em 90 pacientes e no subgrupo DC perineal, 115 em 64 pacientes, respectivamente. Do total de 9 óbitos, 3 ocorreram no grupo RCUI e 6 no DC. A mortalidade geral nas DII foi de 5,7%. Para a DC, 4,5%. No subgrupo de operações abdominais foi de 6,6% e para a RCUI 12,5%. A maior parte dos óbitos estavam relacionados a procedimentos de urgência/emergência, com uso prévio de corticoterapia. A causa mortis em todos os pacientes foi sepse. Conclusões: A taxa de mortalidade cirúrgica nas DII foi de 5,7%, atribuidas pela severidade dos casos.

Mortalidad en enfermedad inflamatoria intestinal / Mortality in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic disease of unknown cause. It has been attributed to an inflammation of the intestinal mucosa due to loss of immunotolerance to commensal intestinal flora in genetically predisposed individuals. It presents short- and long-term complications, impacting the quality of life and increasing patient mortality, although this risk is slightly increased with respect to the general population. Causes of mortality may be due to complications of the disease, secondary to drugs or surgical complications. Mortality associated with the disease, it occurs mainly in the first 5 years of diagnosis, due to the increased risk of acute complications such as severe ulcerative colitis, toxic megacolon and massive digestive hemorrhage. In addition, patients with IBD are at increased risk of digestive tract and extraintestinal neoplasias. Colorectal cancer occurs as a consequence of chronic inflammation of the colonic mucosa. Extraintestinal neoplasms include lung cancer, hematologic malignancies such as lymphoma, cholangiocarcinoma, cervical cancer, and skin cancer. They also present an increased risk of cardiovascular and thromboembolic diseases, associated with the prothrombotic state of these patients. This review aims to describe the main causes of mortality in IBD patients, in order to be able to prevent the disease and provide opportune diagnosis

La enfermedad inflamatoria intestinal (EII) es una enfermedad crónica de causa desconocida. Su etiología se ha atribuido a una inflamación de la mucosa intestinal debido a una pérdida de la inmunotolerancia a la flora intestinal comensal en individuos genéticamente predispuestos. La EII puede presentar complicaciones a corto y largo plazo, lo que puede afectar la calidad de vida y mortalidad de los pacientes, siendo este riesgo levemente mayor con respecto a la población general. Las causas de mortalidad pueden ser consecuencia de las complicaciones propias de la enfermedad, secundaria a fármacos o por complicaciones quirúrgicas. En cuanto a la mortalidad asociada a la enfermedad, se presenta principalmente en los primeros 5 años de diagnóstico, por mayor riesgo de complicaciones agudas como colitis ulcerosa grave, megacolon tóxico y hemorragia digestiva masiva. Además, los pacientes con EII presentan mayor riesgo de neoplasias tanto del tubo digestivo como extraintestinales. El cáncer colorrectal se presenta como consecuencia de la inflamación crónica de la mucosa colónica. Dentro de las neoplasias extraintestinales se encuentran el cáncer de pulmón, neoplasias hematológicas como el linfoma, colangiocarcinoma, cáncer cervicouterino y cáncer de piel. También presentan mayor riesgo de enfermedades cardiovasculares y tromboembólicas, asociadas al estado protrombótico de estos pacientes. Esta revisión tiene como objetivo describir las principales causas de mortalidad en los pacientes con EII, con el fin de poder prevenirlas y diagnosticarlas oportunamente.

Estudo das internações hospitalares por doenças infecciosas intestinais no estado de Alagoas / Study of hospital admissions for intestinal infectious diseases in the state of Alagoas

O presente estudo, sob forma de análise descritiva, tem como objetivos a análise das supostas forças de correlação entre as variáveis e suas implicações, seus diferentes comportamentos, nas questões que envolvem as internações hospitalares observando o comportamento de cada variável, inclusive as construídas sob bases populacionais diferentes, justificando as possíveis causas e consequências, entre a ocorrência das mesmas. Para isto, foram utilizadas variáveis como a "Internação por doença infecciosa intestinal em menor de 1 ano" (Int M), a "Internação por doença infecciosa intestinal em menor de 1 ano, per capita, (Int M PC) e algumas variantes destas, obtidas/construídas de dados secundários do ano de 2010 do DATASUS e SEPLANDE, para efetuar as correlações utilizando o Microsoft Excel. A análise principal apresentou fracas correlações porém não nulas, onde todas as sete variáveis observadas aumentaram os coeficientes de Pearson da primeira com relação a segunda variável. Observou-se a diferença das forças de correlação quando comparadas variáveis construídas sob base populacionais diferentes, bem como a interferência do fator per capita. Além disso, a pesquisa buscou avaliar o problema, identificar as possíveis causas, sugerindo ações específicas e estudos específicos e complementares. Destaca a gravidade do problema para que sejam implementadas políticas públicas específicas e para que mais recursos sejam dirigidos às ações de prevenções das internações hospitalares por doenças infecciosas intestinais no estado de Alagoas. Sugere a ampliação do atendimento da atenção básica em todos os municípios do estado de Alagoas, da quantidade de leitos hospitalares, equipamentos disponíveis para o Sistema Único de Saúde (SUS), para reduzir o número de óbitos decorrentes de tais internações. São limitações deste estudo o pequeno número de variáveis utilizadas e a possibilidade de se proceder com outro teste estatístico para convalidar as que foram efetuadas.(AU)

This study, in the form of descriptive analysis aims to analyze the supposed correlation between variables forces and their implications, their different behavior, on issues involving hospitalizations observing the behavior of each variable, including those built on different population basis, justifying the possible causes and consequences of the occurrence thereof. For this, variables such as "hospitalization for intestinal infectious disease in less than 1 year" (Int M) and "hospitalization for intestinal infectious disease in less than 1 year per capita" (Int PC M) were used, as well as some variants derived from these two, obtained from secondary data by DATASUS and SEPLANDE in 2010, to make correlations using Microsoft Excel. The primary analysis showed weak correlations but not zero, where all seven observed variables increased Pearson's coefficients of the first with respect to the second variable. There was a difference of correlation forces when compared to variables constructed under different population basis, as well as the interference of per capita factor. In addition, the survey sought to assess the problem, identify possible causes, suggesting specific actions and specific and complementary studies. It highlights the seriousness of the problem so that specific public policies and more resources can be implemented as preventive actions for hospitalizations due to intestinal infectious diseases in the state of Alagoas.It also suggests the expansion of primary health care services in all municipalities of the state of Alagoas, the number of hospital beds, equipment available for the Unified Health System (SUS), to reduce the number of deaths from such admissions. Limitations of this study are: the small number of variables used and the possibility of proceeding with another statistical test to validate the ones conducted.(AU)

Similar geographic variations in mortality from peptic ulcer and inflammatory bowel disease.

BACKGROUND: The epidemiology of peptic ulcer and inflammatory bowel disease shows many similar patterns. The aim of the present study was to compare the geographic distribution of mortality from peptic ulcer with that from inflammatory bowel disease. METHODS: Mortality data from 27 countries between 1991 and 2004 were analyzed. The relationships between the geographic distributions of mortality from gastric ulcer, duodenal ulcer, Crohn's disease, and ulcerative colitis were compared using least-squares linear regression analyses. RESULTS: The study revealed a 20- to 30-fold variation in mortality from peptic ulcer and a 60-fold variation in mortality from inflammatory bowel disease among different countries. Mortality from peptic ulcer and inflammatory bowel disease tended to be more common in northern European countries and rare in most countries in Asia and South America. The similar variations of all 4 diseases resulted in the correlations among their geographic distributions being statistically significant. CONCLUSIONS: The similarities in the geographic distributions of gastric ulcer, duodenal ulcer, Crohn's disease, and ulcerative colitis indicate that all 4 diseases may share a common set of risk factors.

Manifestações extra-intestinais da doença intestinal inflamatória / Manifestations extra-instinal of inflammatory bowel diseases

As doenças inflamatórias intestinais inespecíficas (OU) - Doença de Crohn (DC) e Retocolite Ulcerativa (RCU) - são caracterizadas por inflamação intestinal de caráter crônico e recidivante. A etiologia permanece, ainda, obscura, mas sabe-se que a imunorregulação anormal da mucosa intestinal constitui o ponto central para o início e perpetuação da inflamação. A resposta inflamatória sistêmica se manifesta em diferentes formas chamadas "extra-intestinais" como: pele, olhos, articulações e sistemas vascular, músculo-esquelético, respiratório, neurológico, urinário, entre outros. Os autores desse artigo se propõem a realizar uma revisão de tais manifestações