Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis
Introduction: Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn’s disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. Areas covered: An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. Expert opinion: In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.
Novel Prognostic Biomarkers of Mucosal Healing in Ulcerative Colitis Patients Treated With Anti-TNF: Neutrophil-toLymphocyte Ratio and Platelet-to-Lymphocyte Ratio
Lorenzo Bertani 1, Federico Rossari 2, Brigida Barberio 3, Maria Giulia Demarzo 4, Gherardo Tapete 1, Eleonora Albano 1, Giovanni Baiano Svizzero 1, Linda Ceccarelli 5, Maria Gloria Mumolo 5, Chiara Brombin 6, Nicola de Bortoli 1, Massimo Bellini 1, Santino Marchi 1, Giorgia Bodini 4, Edoardo Savarino 3, Francesco Costa 5
Inflamm Bowel Dis. 2020 Sep 18;26(10):1579-1587. doi: 10.1093/ibd/izaa062.
Background: Anti-tumor necrosis factor drugs (anti-TNFs) are widely used for the treatment of ulcerative colitis (UC). However, many patients experience loss of response during the first year of therapy. An early predictor of clinical remission and mucosal healing is needed. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are markers of subclinical inflammation poorly evaluated in UC patients treated with anti-TNFs. The aim of this multicenter study was to evaluate whether NLR and PLR could be used as prognostic markers of anti-TNF treatment response. Methods: Patients with UC who started anti-TNF treatment in monotherapy were evaluated. Patients with concomitant corticosteroid treatment ≥20 mg were excluded. We calculated NLR, PLR, and fecal calprotectin before treatment and after induction. The values of NLR and PLR were correlated with clinical remission and mucosal healing at the end of follow-up (54 weeks) using the Mann-Whitney U test and then multivariate analysis was conducted. Results: Eighty-eight patients were included. Patients who reached mucosal healing after 54 weeks of therapy displayed lower levels of both baseline NLR and PLR (P = 0.0001 and P = 0.04, respectively); similar results were obtained at week 8 (P = 0.0001 and P = 0.001, respectively). Patients who presented with active ulcers at baseline endoscopic evaluation had higher baseline NLR and PLR values compared with those without detected ulcers (P = 0.002 and P = 0.0007, respectively). Conclusions: Both NLR and PLR showed a promising role as early predictors of therapeutic response to anti-TNF therapy in UC patients. If confirmed in larger studies, classification and regression trees proposed in this article could be useful to guide clinical decisions regarding anti-TNF treatment.
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