Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: A multicenter study

Abstract

Active ulcerative colitis (UC) is characterized by activation and infiltration of granulocytes and monocytes/macrophages into the colonic mucosa. The infiltrated leukocytes can cause mucosal damage by releasing degradative proteases, reactive oxygen derivatives, and proinflammatory cytokines. The aim of this trial (conducted in 14 specialist centers) was to assess safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active UC most of whom were refractory to conventional drug therapy. We used a new adsorptive type extracorporeal column (G-1 Adacolumn) filled with cellulose acetate beads (carriers) of 2 mm in diameter, which selectively adsorb granulocytes and monocytes/macrophages. Patients (n = 53) received five apheresis sessions, each of 60 minutes duration, flow rate 30 ml per minute for 5 consecutive weeks in combination with 24.4 +/- 3.60 mg prednisolone (mean +/- SE per patient per day, baseline dose). During 60 minutes apheresis, 26% of granulocytes, 19.5% of monocytes and 2% of lymphocytes adsorbed to the carriers. At week 7, 58.5% of patients had remission or improved, the dose of prednisolone was reduced to 14.2 +/- 2.25 mg (n = 37). The apheresis treatment was fairly safe, only eight non-severe side effects (in 5 patients) were reported. Based on our results, we believe that in patients with active severe UC, patients who are refractory to conventional drugs, granulocyte and monocyte adsorption apheresis is a useful adjunct to conventional therapy. This procedure should have the potential to allow tapering the dose of corticosteroids, shorten the time to remission and delay relapse.

G Protein-Coupled Receptor 43 Is Essential for Neutrophil Recruitment during Intestinal Inflammation

“…Whereas anti-TNF therapy in CD indirectly lowers PMN concentrations in the intestinal mucosa (55), direct Ab-mediated integrin neutralization has resulted in promising efficacy profiles in both CD and ulcerative colitis (56,57). A small clinical trial using a small molecule inhibitor of c-Raf, a critical upstream kinase of p38 MAPK and JNK, showed beneficial effects in CD and included a reduction of activated PMNs in the inflamed mucosa of the responders (58,59).…”

Depletion of neutrophils blocks the recruitment of antigen-nonspecific cells into the liver without affecting the antiviral activity of hepatitis B virus-specific cytotoxic T lymphocytes

“…Furthermore, the fact that PMN depletion is associated with maintenance of CTL-dependent antiviral effects but diminished tissue damage may help the design of potential immunotherapeutic approaches for the treatment of HBV infection in chronically infected patients. This should also be viewed in light of the fact that PMN depletion is a relatively simple procedure that has been performed in humans for the treatment of conditions such as inflammatory bowel disease and ulcerative colitis (29).…”

Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study

“…13 Therefore, reducing granulocytes and monocytes by apheresis has the potential for improving the bowel inflammation and patient status. Recently, granulocyte and monocyte adsorptive apheresis (GMCAP) has been tried as a novel approach for autoimmune diseases such as rheumatoid arthritis 14,15 and UC [16][17][18][19][20][21][22] which poorly respond to medication. Several studies have assessed safety and efficacy of GMCAP for patients with active UC.…”

“…Several studies have assessed safety and efficacy of GMCAP for patients with active UC. Shimoyama et al 18 reported that 58.5% of 53 patients, most of whom were refractory to conventional drug therapy had remission or improved after five apheresis sessions and the daily dose of prednisolone was reduced. Only eight non-severe adverse effects were noted in five patients.…”