Randomised, Double-blind, Placebo-controlled Trial of CCR9-targeted Leukapheresis Treatment of Ulcerative Colitis Patients. (2nd November 2016)

• Record Type: Journal Article
• Authors: Eberhardson, Michael; Karlén, Per; Linton, Ludvig; Jones, Petra; Lindberg, Annelie; Kostalla, Martina Jones; Lindh, Emma; Odén, Anders; Glise, Hans; Winqvist, Ola
• Is Part Of: Journal of Crohn's and colitis. Volume 11:Number 5(2017:May)
• Page Start: 534
• Page End: 542
• Publication Date: 2016-11-02
• Subjects: Ulcerative colitis -- leukapheresis -- chemokine receptor 9; Inflammatory bowel diseases -- Periodicals; 616.344005
• DOI: 10.1093/ecco-jcc/jjw196
• Languages: English
• ISSNs: 1873-9946

Abstract

Abstract: Background and Aims: Ulcerative colitis patients display increased numbers of circulating pro-inflammatory monocyte human leukocyte antigen-DR [HLA-DR hi ] monocytes expressing high levels of the gut-homing C-C chemokine receptor 9 [CCR9] and tumour necrosis factor [TNF]-α. The aim of this first-in-human, double-blind, randomised, placebo-controlled trial was to evaluate selective removal of circulating CCR9-expressing monocytes by leukapheresis in patients with moderate to severe ulcerative colitis, with regards to safety, tolerability, and immunological response. Methods: Patients with ulcerative colitis were treated every second day with leukapheresis during five sessions with a C-C chemokine ligand 25 [CCL25; CCR9 ligand] column or a placebo column. Results: No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DR hi cells decreased significantly in the active treatment group [ p = 0.0391] whereas no statistically significant change was seen in the placebo group [ p = 0.4688]. There was a significant decrease of HLA-DR hi monocytes in the active group compared with the placebo group when corrected for the imbalance in weight between the groups [ p = 0.0105]. Mayo score decreased in the active group [ p = 0.0156] whereas the change in the placebo group was not significant [ p = 0.1250]. Mayo score ≤ 3 was observed in five out of 14 patients [35.7%] in the active group compared with one out of eight [12.5%] receiving placebo. The number of responders in the active treatment group was eight out of 14 patients [57.1%], whereas in the corresponding placebo group three out of eight patients [37.5%] responded to placebo. A dose-response correlation was observed between the blood volume processed and clinical outcome. Conclusion: This clinical induction trial using CCL25-tailored leukapheresis demonstrates a safe and effective removal of activated monocytes with a clinical effect in patients with ulcerative colitis.