Safety, Effectiveness, and Treatment Persistence of Subcutaneous Vedolizumab in IBD: A Multicenter Study From the United Kingdom.

BACKGROUND AND AIMS: Despite intravenous (IV) vedolizumab being established for treatment of inflammatory bowel disease (IBD), the novel subcutaneous (SC) route of administration may provide numerous incentives to switch. However, large-scale real-world data regarding the long-term safety and effectiveness of this strategy are lacking. METHODS: IBD patients on IV vedolizumab across 11 UK sites agreed to transition to SC injections or otherwise continued IV treatment. Data regarding clinical disease activity (Simple Clinical Colitis Activity Index, partial Mayo score, and modified Harvey-Bradshaw Index), biochemical markers (C-reactive protein and calprotectin), quality of life (IBD control), adverse events, treatment persistence, and disease-related outcomes (namely corticosteroid use, IBD-related hospitalization, and IBD-related surgery) were retrospectively collected from prospectively maintained clinical records at baseline and weeks 8, 24, and 52. RESULTS: Data from 563 patients (187 [33.2%] Crohn's disease, 376 [66.8%] ulcerative colitis; 410 [72.8%] SC, 153 [27.2%] IV) demonstrated no differences in disease activity, remission rates, and quality of life between the SC and IV groups at all time points. Drug persistence at week 52 was similar (81.1% vs 81.2%; P = .98), as were rates of treatment alteration due to either active disease (12.2% vs 8.9%; P = .38) or adverse events (3.3% vs 6.3%; P = .41). At week 52, there were equivalent rates of adverse events (9.8% vs 7.8%; P = .572) and disease-related outcomes. IBD control scores were equivalent in both IV-IV and IV-SC groups. CONCLUSIONS: Switching to SC vedolizumab appears as effective, safe, and well tolerated as continued IV treatment and maintains comparable disease control and quality of life as IV treatment at 52 weeks.

Human monocytes and macrophages regulate immune tolerance via integrin αvß8-mediated TGFß activation.

Monocytes are crucial immune cells involved in regulation of inflammation either directly or via differentiation into macrophages in tissues. However, many aspects of how their function is controlled in health and disease are not understood. Here we show that human blood monocytes activate high levels of the cytokine TGFß, a pathway that is not evident in mouse monocytes. Human CD14+, but not CD16+, monocytes activate TGFß via expression of the integrin αvß8 and matrix metalloproteinase 14, which dampens their production of TNFα in response to LPS. Additionally, when monocytes differentiate into macrophages, integrin expression and TGFß-activating ability are maintained in anti-inflammatory macrophages but down-regulated in pro-inflammatory macrophages. In the healthy human intestine, integrin αvß8 is highly expressed on mature tissue macrophages, with these cells and their integrin expression being significantly reduced in active inflammatory bowel disease. Thus, our data suggest that integrin αvß8-mediated TGFß activation plays a key role in regulation of monocyte inflammatory responses and intestinal macrophage homeostasis.

Natural history of azathioprine-associated lymphopenia in inflammatory bowel disease patients: a prospective observational study.

INTRODUCTION: Azathioprine (AZA) is commonly used in inflammatory bowel disease (IBD) patients. Lymphopenia is a recognized effect of this treatment, but lymphopenia-related complications in IBD patients have not been widely reported. The incidence and progression of AZA-induced lymphopenia in IBD patients is not well described. There is no consensus on its optimal management in this group. AIMS AND METHODS: We assessed the incidence and progression of lymphopenia and its related complications in a cohort of IBD patients over a 14-month period in two large tertiary gastroenterology units. Analysis of prospectively collected data was performed. RESULTS: Fifty-two patients were studied prospectively with a median age of 34 years. Eighteen patients (34.6%) developed lymphopenia (<1.0×10(9)/l) during the course of treatment and 10 of them had severe lymphopenia (<0.6×10(9)/l). Lymphopenia lasted on average 85.4 days and spontaneously resolved in 13 patients. No lymphopenia related-complications were documented. Patients treated with steroids had a significantly higher rate of lymphopenia (83.3 vs. 44.1%, P=0.0083). CONCLUSION: Lymphopenia is common among IBD patients treated with AZA. However, it did not seem to be associated with a higher risk of opportunistic infections and spontaneously resolved in the majority of cases.