The SPOSIB SB2 Sicilian Cohort: Safety and Effectiveness of Infliximab Biosimilar SB2 in Inflammatory Bowel Diseases, Including Multiple Switches.
SPOSIB SB2 西西里队列: 英夫利昔单抗生物类似物 SB2 在炎症性肠病中的安全性和有效性，包括多个开关。
- 作者列表："Macaluso FS","Fries W","Viola A","Centritto A","Cappello M","Giuffrida E","Privitera AC","Piccillo G","Magnano A","Vinci E","Vassallo R","Trovatello A","Belluardo N","Giangreco E","Camilleri S","Garufi S","Bertolami C","Ventimiglia M","Renna S","Orlando R","Rizzuto G","Orlando A
BACKGROUND:No data on the recently introduced infliximab (IFX) biosimilar SB2 in inflammatory bowel disease (IBD) are available. METHODS:The Sicilian Prospective Observational Study of Patients With IBD Treated With Infliximab Biosimilar SB2 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease. All consecutive IBD patients starting the IFX biosimilar SB2 from its introduction in Sicily (March 2018) to September 2019 (18 months) were enrolled. RESULTS:Two hundred seventy-six patients (Crohn disease: 49.3%, ulcerative colitis: 50.7%) were included: 127 (46.0%) were naïve to IFX and naïve to anti-tumor necrosis factor medications (anti-TNFs), 65 (23.5%) were naïve to IFX and previously exposed to anti-TNFs, 17 (6.2%) were switched from an IFX originator to SB2, 43 (15.6%) were switched from the biosimilar CT-P13 to SB2, and 24 (8.7%) were multiply switched (from IFX originator to CT-P13 to SB2). The cumulative number of infusions of SB2 was 1798, and the total follow-up time was 182.7 patient-years. Sixty-seven serious adverse events occurred in 57 patients (20.7%; incidence rate: 36.7 per 100 patient-year), and 31 of these events caused the withdrawal of the drug. The effectiveness after 8 weeks of treatment was evaluated in patients naïve to IFX (n = 192): 110 patients (57.3%) had steroid-free remission, while 56 patients had no response (29.2%). At the end of follow-up, 72 patients (26.1%) interrupted the treatment, without significant differences in treatment persistency estimations between the five groups (log-rank P = 0.15). CONCLUSIONS:The safety and effectiveness of SB2 seem to be overall similar to those reported for the IFX originator and CT-P13.
背景: 没有关于最近引进的英夫利昔单抗 (IFX) 生物类似物 SB2 在炎症性肠病 (IBD) 中的数据。 方法: 对接受英夫利昔单抗生物类似物 SB2 治疗的 IBD 患者进行的西西里前瞻性观察研究是在西西里炎症性肠病网络队列中进行的一项多中心、观察性、前瞻性研究。入选从 IFX 生物仿制药 SB2 在西西里岛引入 (2018年3月) 至 2019年9月 (18 个月) 开始的所有连续 IBD 患者。 结果: 49.3% 例 (50.7%) 患者 (克罗恩病: 127，溃疡性结肠炎: 46.0%) 初治 IFX 和初治抗肿瘤坏死因子药物 (抗 TNFs)，65 例 (23.5%) 初治 IFX 和既往暴露于抗 TNFs，17 例 (6.2%)从 IFX 原点切换到 SB2，43 例 (15.6%) 从生物仿制药 CT-P13 切换到 SB2，24 例 (8.7%) 从 IFX 原点切换到 CT-P13 SB2。SB2 的累积输注次数为 1798 次，总随访时间为 182.7 患者年。57 例患者发生了 67 例严重不良事件 (20.7%; 发病率: 36.7/100 患者年)，其中 31 例事件导致药物停药。在未接受 IFX 的患者 (n = 192) 中评估治疗 8 周后的有效性: 110 例患者 (57.3%) 无类固醇缓解, 而 56 例患者无反应 (29.2%)。随访结束时，72 例患者 (26.1%) 中断了治疗，5 组间治疗持续性估计值无显著差异 (log-rank P = 0.15)。 结论: SB2 的安全性和有效性似乎总体上与 IFX 起始者和 CT-P13 报道的相似。
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.