Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Quality of life in patients with inflammatory bowel disease: importance of clinical, demographic and psychosocial factors

Context - Inflammatory bowel disease causes physical and psychosocial consequences that can affect the health related quality of life. Objectives - To analyze the relationship between clinical and sociodemographic factors and quality of life in inflammatory bowel disease patients. Methods - Ninety two patients with Crohn’s disease and 58 with ulcerative colitis, filled in the inflammatory bowel disease questionnaire (IBDQ-32) and a questionnaire to collect sociodemographic and clinical data. The association between categorical variables and IBDQ-32 scores was determined using Student t test. Factors statistically significant in the univariate analysis were included in a multivariate regression model. Results - IBDQ-32 scores were significantly lower in female patients (P<0.001), patients with an individual perception of a lower co-workers support (P<0.001) and career fulfillment (P<0.001), patients requiring psychological support (P = 0.010) and pharmacological treatment for anxiety or depression (P = 0.002). A multivariate regression analysis identified as predictors of impaired HRQOL the female gender (P<0.001) and the perception of a lower co-workers support (P = 0.025) and career fulfillment (P = 0.001). Conclusion - The decrease in HRQQL was significantly related with female gender and personal perception of disease impact in success and social relations. These factors deserve a special attention, so timely measures can be implemented to improve the quality of life of patients.Contexto - A doença inflamatória intestinal acarreta consequências físicas, psicológicas e sociais que podem afetar a qualidade de vida dos doentes. Objetivo - Avaliar a relação entre os fatores clínicos, demográficos e psicossociais e a qualidade de vida na doença inflamatória intestinal. Métodos - Um total de 150 doentes, 92 com doença de Crohn e 58 com colite ulcerosa, preencheram um questionário para avaliação da qualidade de vida na doença inflamatória intestinal (IBDQ-32) e um questionário para recolha de dados sociodemográficos e clínicos. A associação entre variáveis categóricas e o IBDQ-32 foi determinada com o teste t-Student. Variáveis estatisticamente significativas na análise univariada foram incluídas no modelo de regressão linear múltipla. Resultados - A análise univariada revelou uma qualidade de vida significativamente menor nas mulheres (P<0,001) e nos doentes com uma perceção individual de falta de compreensão pelos colegas de trabalho (P<0,001) e de diminuição do sucesso laboral (P<0,001). Doentes com necessidade de apoio psicológico (P = 0,010) e tratamento farmacológico da ansiedade e/ou depressão (P = 0,002) também apresentaram IBDQ-32 scores significativamente mais baixos. A análise de regressão linear múltipla identificou como preditores de diminuição da qualidade de vida o sexo feminino (P<0,001), perceção individual da falta de compreensão pelos colegas de trabalho (P = 0,025) e de diminuição do sucesso laboral (P = 0,001). Conclusões - A diminuição da qualidade de vida relaciona-se significativamente com o sexo feminino e a percepção pessoal de impacto da doença no sucesso e relações laborais. Estes fatores merecem uma atenção acrescida para que atempadamente se possam implementar medidas que possibilitem a melhoria da qualidade de vida destes doentes.(undefined