Treating inflammatory bowel disease by adsorptive leucocytapheresis: A desire to treat without drugs

Abstract

Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 21^st century reminds us of phlebotomy as a major medical practice at the time of Hippocrates. However, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines and achieve disease remission. The bottom line is that by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage and become refractory to medications, many patients should respond to GMA and avoid pharmacologics. This should fulfill the desire to treat without drugs.

Keywords: Inflammatory bowel disease; Myeloid lineage leucocytes; Adsorptive granulocytes/monocytes apheresis; Corticosteroid sparing effect; Complement activation fragments; Treating inflammatory bowel disease without drugs

Core tip: The efficacy of anti-tumour necrosis factor-α biologics has validated the role of inflammatory cytokines in the exacerbation of inflammatory bowel disease (IBD). However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA). Therefore, in patients with IBD, there is a scope for removing from the body the sources of pro-inflammatory cytokines, and this should fulfill the desire to treat without drugs. Therefore, by introducing GMA at an early stage following the onset of IBD or before patients develop extensive mucosal damage, many patients should respond to GMA and avoid pharmacologics.