Golimumab 在溃疡性结肠炎患者真实世界中的实践: 12 个月的结果。
- 作者列表："Teich N","Grümmer H","Jörgensen E","Liceni T","Holtkamp-Endemann F","Fischer T","Hohenberger S
BACKGROUND:The introduction of biologics has revolutionized the management of the chronic inflammatory bowel disease, ulcerative colitis (UC), with many patients experiencing significant improvements not only in their symptoms but in other outcomes relevant to individuals and society as a whole. In Germany, there are no prospective data > 3 mo that assess the work productivity, daily activities and quality of life (QoL) of patients with moderate-to-severe UC treated with golimumab. AIM:To assess change in work productivity, capacity for daily activities and QoL in UC patients treated with golimumab in Germany. METHODS:The validated Work Productivity Activity Impairment (WPAI) Questionnaire was used to analyze the change in work productivity, the capacity for daily activities after three months (primary endpoint) and disease specific and health related QoL (HRQoL) up to 1 year (secondary endpoints). The changes in work productivity and activity impairment were evaluated every three months until month twelve compared to baseline. Disease-specific and health-related QoL were assessed with the inflammatory bowel disease questionnaire and with the short-form 12 health survey questionnaire (SF-12). RESULTS:This prospective non-interventional study included 287 patients. The analysis population was comprised of 282 patients who had completed at least two visits. At baseline, 61% of patients had moderate UC and 18% had severe UC. Furthermore, 75% of patients worked full-time or part-time at baseline. A total of 212 patients who were employed at the start of the study (employed population) were evaluated for the primary endpoint. Golimumab significantly reduced all WPAI sub-scores compared to baseline after three, six, nine and twelve months after the start of treatment (P < 0.0001). In addition, disease-specific QoL and HRQoL, as measured by the SF-12 questionnaire, improved significantly with golimumab at all evaluation times (P < 0.0001 in each case vs baseline). CONCLUSION:Treatment of moderate-to-severe UC with golimumab leads to significant improvements in patient´s work productivity, daily activity and QoL over twelve months.
背景: 生物制剂的引入彻底改变了慢性炎症性肠病、溃疡性结肠炎 (UC) 、随着许多患者不仅在症状方面，而且在与个人和整个社会相关的其他结局方面都经历了显著的改善。在德国，没有前瞻性数据> 3 mo 评估接受戈利木单抗治疗的中重度 UC 患者的工作效率、日常活动和生活质量 (QoL)。 目的: 评估德国接受戈利木单抗治疗的 UC 患者工作效率、日常活动能力和 QoL 的变化。 方法: 使用经过验证的工作生产力活动障碍 (WPAI) 问卷分析工作生产力的变化，三个月后的日常活动能力 (主要终点) 和疾病特异性和健康相关 QoL (HRQoL) 长达 1 年 (次要终点)。与基线相比，每三个月评估一次工作生产率和活动损伤的变化，直到第 12 个月。使用炎症性肠病问卷和 12 健康调查问卷 (SF-12) 评估疾病特异性和健康相关的生活质量。 结果: 本前瞻性非干预性研究共纳入 287 例患者。分析人群包括至少完成两次访视的 282 例患者。在基线时，61% 的患者患有中度 UC，18% 的患者患有重度 UC。此外，75% 的患者在基线时全职或兼职工作。对研究开始时雇用的 212 例患者 (雇用人群) 进行了主要终点评估。Golimumab 在治疗开始后 3 、 6 、 9 和 12 个月与基线相比显著降低了所有 WPAI 分 (P <0.0001)。此外，通过 SF-12 问卷测量的疾病特异性 QoL 和 HRQoL 在所有评估时间均显著改善 (与基线相比，P <0.0001)。 结论: 使用戈利木单抗治疗中重度 UC 可显著改善患者的工作效率、日常活动能力和 QoL。
METHODS::Chronic diseases, including inflammatory bowel disease (IBD) urgently need new biomarkers as a significant proportion of patients, do not respond to current medications. Inflammation is a common factor in these diseases and microbial sensing in the intestinal tract is critical to initiate the inflammation. We have identified ELMO1 (Engulfment and Cell Motility Protein-1) as a microbial sensor in epithelial and phagocytic cells that turns on inflammatory signals. Using a stem-cell-based "gut-in-a-dish" coculture model, we studied the interactions between microbes, epithelium and monocytes in the context of IBD. To mimic the in-vivo cell physiology, enteroid-derived monolayers (EDMs) were generated from the organoids isolated from WT and ELMO1-/- mice and colonic biopsies of IBD patients. The EDMs were infected with the IBD-associated microbes to monitor the inflammatory responses. ELMO1-depleted EDMs displayed a significant reduction in bacterial internalization, a decrease in pro-inflammatory cytokine productions and monocyte recruitment. The expression of ELMO1 is elevated in the colonic epithelium and in the inflammatory infiltrates within the lamina propria of IBD patients where the higher expression is positively correlated with the elevated expression of pro-inflammatory cytokines, MCP-1 and TNF-α. MCP-1 is released from the epithelium and recruits monocytes to the site of inflammation. Once recruited, monocytes require ELMO1 to engulf the bacteria and propagate a robust TNF-α storm. These findings highlight that the dysregulated epithelial ELMO1→MCP-1 axis can serve as an early biomarker in the diagnostics of IBD and other inflammatory disorders.
METHODS:BACKGROUND:Peripheral blood eosinophilia (PBE) is a biomarker of an aggressive multiyear natural history in adults with inflammatory bowel diseases (IBDs). Additionally, PBE at diagnosis is associated with higher disease activity in pediatric-onset IBD. We sought to determine if PBE can function as a biomarker of long-term disease severity in pediatric-onset IBD patients who are followed into adulthood. METHODS:We analyzed a consented, prospective, natural history IBD registry at an adult tertiary center from 2009 to 2018. Prevalence of PBE was evaluated in both pediatric- and adult-onset IBD patients. Demographics, clinical characteristics, and health care utilization data were compared in patients with and without PBE. RESULTS:Among 2800 adult IBD patients, 23.4% had pediatric-onset disease. PBE was found in 34% of the pediatric-onset patients compared with 26.8% of the adult-onset IBD patients (P < 0.001). In the pediatric-onset IBD cohort, PBE was associated with higher rates of allergies (P < 0.0001), but not of asthma, allergic rhinitis, or primary sclerosing cholangitis. In the adult IBD patients with pediatric-onset disease, PBE was associated with higher rates of C-reactive protein elevation (P < 0.0001), erythrocyte sedimentation rate elevation (P < 0.0001), higher health care utilization, and higher average health care charges per year (P < 0.00001). CONCLUSIONS:Peripheral blood eosinophilia was more prevalent in adult IBD patients with pediatric-onset compared with adult-onset disease. Among all IBD patients with long-term follow-up, PBE defined a subgroup with more severe illness. These data suggest that PBE may be a biomarker for a high-risk subgroup with high cost trajectory and long-term severity in pediatric-onset IBD that persists into adulthood.
METHODS::Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with a complex pathogenesis, affecting people of all ages. They are characterized by alternating phases of clinical relapse and remission, depending on the fine balance between immune cells and the gut microbiota. The cross talk between cells of the immune system and the gut microbiota can result in either tolerance or inflammation, according to multifactorial triggers, ranging from environmental factors to genetic susceptibility. Glucocorticoid (GC) administration remains the first-line treatment for IBDs, although long-term use is limited by development of serious adverse effects. Recently, new alternative pharmacological therapies have been developed, although these are not always effective in IBD patients. There is a constant demand for effective new drug targets to guarantee total remission and improve the quality of life for IBD patients. The glucocorticoid-induced leucine zipper (GILZ) has been implicated as a promising candidate for this purpose, in view of its powerful anti-inflammatory effects that mimic those of GCs while avoiding their unwanted adverse reactions. Here we present and discuss the latest findings about the involvement of GILZ in IBDs.