Granulomonocytapheresis as a cell-dependent treatment option for patients with inflammatory bowel disease: Concepts and clinical features for better therapeutic outcomes.

ABSTRACT

Ulcerative colitis (UC) and Crohn's disease (CD) are major phenotypes of the chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms. The chronic nature of IBD means that patients require life-long medications, and this may lead to drug dependency, loss of response together with adverse side effects as additional morbidity factors. The efficacy of antitumour necrosis factor (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation and perpetuation of IBD. However, cytokines are released by myeloid lineage leucocytes like the CD14+ CD16+ monocyte phenotype. Additionally in IBD, myeloid leucocytes are elevated with activation behavior, while lymphocytes are compromised. Therefore, patients' leucocytes appear logical targets of therapy. Adsorptive granulomonocytapheresis (GMA) with an Adacolumn uses carriers, which interact with the Fcγ receptor expressing leucocytes and deplete the elevated myeloid leucocytes, while the neutrophils, which re-enter the circulation via the Adacolumn outflow (≥40%) are phagocytosed by CD19 B-cells to become interleukin (IL)-10 producing Bregs or CD19high CD1Dhigh B-cells. IL-10 is an anti-inflammatory cytokine. GMA has been applied to treat patients with IBD. The efficacy outcomes have been impressive as well as disappointing, the clinical response to GMA defines the patients' disease course and severity at entry. Efficacy outcomes in patients with deep ulcers together with extensive loss of the mucosal tissue are not encouraging, while patients without these features respond well and attain a favorable long-term disease course. Accordingly, for responder patients, GMA fulfills a desire to be treated without drugs.