Adacolumn leucocytapheresis for ulcerative colitis: clinical and endoscopic features of responders and unresponders

Abstract

Cytokines such as TNF-α have a validated role in the immunopathogensis of ulcerative colitis (UC), and intercepting inflammatory cytokines is currently the best option for maximizing treatment efficacy. One of the major sources of inflammatory cytokines are myeloid linage leucocytes (granulocytes, monocytes), which are present in great numbers in the colonic tissue. Their selective depletion by adsorptive granulocyte, monocyte apheresis (GMA), should be therapeutic in patients with UC, although until now efficacy outcomes have been both encouraging and disappointing. The authors’ view is that in patients with UC, there is an evolving scope for therapeutic opportunity based on taking away the sources of inflammatory cytokines, also considering the favorable safety profile of GMA.

Keywords:

• colonoscopy
• granulocyte and monocyte apheresis
• loss of mucosal tissue
• mucosal biopsy
• neutrophils and monocytes
• neutrophil infiltration
• ulcerative colitis

Acknowledgements

Editorial assistance for the preparation of this manuscript was provided by Ambra Corti and Luca Giacomelli.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• Patients with active ulcerative colitis (UC) present different responses to medical interventions depending on clinical and endoscopic disease severity.

• Cytokines like TNF-α have a validated role in the immunopathogensis of UC, and intercepting inflammatory cytokines is currently the best option for maximizing treatment efficacy.

• The major sources of inflammatory cytokines are granulocytes and monocytes, which are present in great number in the colonic tissue.

• Their selective depletion by adsorptive GMA should be therapeutic in patients with UC, although until now efficacy outcomes have been both encouraging and disappointing.

• Most patients with a fair level of intact mucosal tissue appeared to respond well and be spared from multiple drug therapy.

• The best responders were patients with the first UC episode and short duration of disease and steroid-naïve patients.

• Patients with deep colonic lesions, extensive loss of the mucosal tissue or prolonged exposure to multiple drugs like corticosteroids were identified as unlikely responders to GMA.

• Our view is that in patients with UC, there is an evolving scope for therapeutic opportunity based on taking away the sources of inflammatory cytokines, also considering the favorable safety profile of GMA.