Takumi Fukuchi , Kousaku Kawashima , Hideaki Koga , Ran Utsunomiya, Kohei Sugiyama , Keiji Shimazu , Takaaki Eguchi , Shunji Ishihara J Clin Biochem Nutr. 2022 Mar;70(2):197-204. doi: 10.3164/jcbn.21-112. Epub 2021 Dec 25.
Induction of mucosal healing by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids in patients with ulcerative colitis: long-term remission maintenance after induction by GMA and efficacy of GMA re-treatment upon relapse
This study examined the long-term maintenance rate after inducing remission by intensive granulocyte/monocyte adsorptive apheresis (GMA) without use of corticosteroids (CS) and GMA re-treatment efficacy in the same patients upon relapse with ulcerative colitis. Patients who achieved clinical remission and mucosal healing (MH) by first-time intensive GMA (first GMA) without CS were enrolled. The cumulative non-relapse survival rate up to week 156 was calculated. Patients with relapse during the maintenance period underwent second-time intensive GMA (second GMA) without CS. Clinical remission and MH rates following second GMA were compared to those following first GMA in the same patients. Of the 84 patients enrolled, 78 were followed until week 156 and 34 demonstrated relapse. The cumulative non-relapse survival rate by week 156 was 56.4%. Clinical remission and MH rates after second GMA did not differ from those after first GMA in the same patients (week 6: clinical remission, 100% vs 88.4%, p = 0.134; MH, 100% vs 84.8%, p = 0.074). In conclusion, MH induction by intensive GMA without use of CS in ulcerative colitis patients contributes to subsequent long-term clinical remission maintenance. GMA re-treatment efficacy was comparable to that of first GMA in the same patients who had relapse.
Inflammatory bowel disease patients experiencing a loss of response to infliximab regain long-term response after undergoing granulocyte/monocyte apheresis: A case series.
To our best knowledge, this is the first report of adding a non-drug GMA to restore the efficacy of infliximab. The outcomes, albeit in three cases, are relevant in therapeutic settings and should inspire further studies in a larger number of patients.
In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patients
Background: The aetiology of ulcerative colitis is inadequately understood, and drug therapy has been empirical rather than based on sound understanding of disease aetiology. This has been a major factor for refractoriness and adverse drug effects as additional complications. However, ulcerative colitis by its very nature is exacerbated and perpetuated by inflammatory cytokines, which are released by peripheral granulocytes and monocytes as well. Additionally, active ulcerative colitis is often associated with elevated peripheral granulocytes and monocytes with activation behaviour and are found in vast numbers within the colonic mucosa. Hence, from the clinicopathologic viewpoint, granulocytes and monocytes are appropriate targets for therapy in ulcerative colitis. Based on this thinking, an Adacolumn has been developed for depleting excess granulocytes and monocytes by adsorption. Methods: By colonoscopy, biopsy and histology, we investigated the impact of granulocyte and monocyte adsorption (GMA) on the mucosal level of granulocytes and monocytes in patients with active ulcerative colitis. Forty-five patients (26 steroid naïve and 19 steroid-dependent), mean age 44.7 yr, were included. Twenty patients had total colitis and 25 had left-sided colitis. Each patient was given up to 11 GMA sessions over 12 weeks. No patient received additional medications within 4 weeks (steroid) to 8 weeks (other immunosuppressants) prior to entry or during the GMA course. Colonoscopy together with biopsy was done at entry and within 2 weeks after the last GMA session. Results: At entry, the mean clinical activity index was 12.6; range 10-16. A total of 400 colonic biopsies were examined, which revealed massive infiltration of the colonic mucosa by granulocytes, and GMA was associated with striking reduction of granulocytes in the mucosa. At week 12, 33 of 45 patients (73.3%, P<0.01) had achieved clinical remission (the mean clinical activity index <or= 4). Colonoscopy revealed that most non-responders had deep colonic ulcers and extensive loss of the mucosal tissue. The response rate in steroid naïve subgroup was 22 of 26 patients (84.6%, P<0.005) and in steroid-dependent was 11 of 19 (57.9%, P<0.05 and P=0.02154 for steroid naïve vs. steroid-dependent). Patients who achieved remission could continue with their salicylates. On average, remission was sustained for 7.8 months in all 33 responders. Conclusions: This is the first report showing a striking difference in clinical response to GMA between steroid naïve and steroid-dependent patients. Further, patients with deep colonic ulcers together with extensive loss of the mucosal tissue are not like to respond to GMA.
Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study
Corticosteroid therapy of ulcerative colitis (UC) is associated with frequent adverse side effects and poor quality of life. Recently, adsorptive granulocyte and monocyte/macrophage apheresis has shown efficacy in patients with severe steroid refractory UC. The objective of this study was to investigate if, instead of corticosteroids, adsorptive leukocytapheresis has efficacy as the first-line therapy for steroid-naïve patients with active UC. Twenty patients, aged 15-49 years, with a mean clinical activity index (CAI) of 8.6 were recruited. Adsorptive leukocytapheresis was done with Adacolumn, which contains cellulose acetate beads as adsorptive carriers for granulocytes and monocytes (FcgammaR and complement receptors expressing leukocytes). Each patient received 6 to 10 leukocytapheresis sessions of 60-min duration, at 2 sessions/week. Efficacy was assessed 1 week after the last session. Post treatment, the mean CAI was 3.0 (P = 0001), and 17 of 20 patients (85%) were in remission. There were significant falls in C-reactive protein (P = 0.0003), total white cell counts (P = 0.003), neutrophils (P = 0.0029), and monocytes (P = 0.0038), an increase in lymphocytes (P = 0.001), and increases in the blood levels of soluble TNF-alpha receptors I (P = 0.0007) and II (P = 0.0045) in the column outflow (blood return to the patients). Further, at 8 months, 60% of patients had maintained their remission. No severe side effects were reported. In conclusion, adsorptive leukocytapheresis should reduce corticosteroid therapy in patients with moderate UC; cases with early-stage active disease may benefit most.
Contact UsFor more informationContact Us