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Randomized, double-blind, placebo-controlled trial of CCR9-targeted leukapheresis treatment of ulcerative colitis patients

Department of Gastroenterology, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Medicine, Karolinska Institutet, Stockholm, Sweden. Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Karolinska Institutet, Danderyd Hospital, Sweden; ITH, Karolinska University Hospital, Stockholm, Sweden. ITH, Karolinska University Hospital, Stockholm, Sweden; Mathematical Sciences, Chalmers University of Technology, Gothenburg, Sweden.

Journal of Crohn's & Colitis. 2016;11((5):):534-542

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Abstract
BACKGROUND AND AIMS Ulcerative colitis patients display increased number of circulating pro-inflammatory HLA-DRhi monocytes expressing high levels of the gut homing chemokine receptor CCR9 and TNF-alpha. The aim of this first-in-man double blind randomized 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 5 sessions with CCL25 (CCR9 ligand) column or a placebo column. RESULTS No major safety concerns were raised and the procedure was well tolerated. Pro-inflammatory HLA-DRhi cells decreased significantly in the active treatment group (p=0.0391) while no statistically significant change was seen in the placebo group (p=0.4688). There was a significant decrease of HLA-DRhi monocytes in the active group compared to 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 to 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.
Study details
Language : English
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine