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 CD19highCD1Dhigh 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.

Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis

“…GMA was performed with the Adacolumn (JIMRO Co., Ltd., Takasaki City, Japan) which contains cellulose acetate beads as leukocytapheresis carriers for myeloid lineage leukocytes . Each patient received up to 10 GMA sessions, at one, two, or three sessions per week.…”

“…Nowadays, in Japan as well as in the European countries, GMA is favored by patients for its safety profile as well as for being a nonpharmacologic strategy for treating patients with active UC. The primary action of GMA for inducing anti‐inflammatory effect is to selectively deplete elevated granulocytes and monocyte as blood passes through the column . GMA initiates generation of regulatory B and T cells , which are the key requirements for a normal immune function.…”

“…The primary action of GMA for inducing anti‐inflammatory effect is to selectively deplete elevated granulocytes and monocyte as blood passes through the column . GMA initiates generation of regulatory B and T cells , which are the key requirements for a normal immune function. Further, unadsorbed leukocytes which pass through the column show downregulation of adhesion molecules and reduction of inflammatory cytokine production .…”

The combination of granulocyte‐monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis?

“…In a randomized, double‐blind, sham‐controlled clinical trial, granulocyte‐monocyte apheresis (GMA) did not demonstrate statistically significant differences in terms of clinical response, endoscopic remission, or quality of life as compared to placebo . Nonetheless, further data from observational studies have shown higher response rates, with better results in steroid‐dependent UC with a short disease duration . Recently, it has been suggested that the combination of GMA and anti‐tumor necrosis factor (TNF)‐alfa agents could regain the response in patients with LOR to these drugs .…”

“…5 Nonetheless, further data from observational studies have shown higher response rates, with better results in steroid-dependent UC with a short disease duration. 6 Recently, it has been suggested that the combination of GMA and anti-tumor necrosis factor (TNF)-alfa agents could regain the response in patients with LOR to these drugs. 7 The evidence of this potential approach with VDZ has also been described as a feasible option in this clinical situation, but the evidence comes only from case reports.…”