Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone

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Abstract

Background: The number of ulcerative colitis (UC) patients is increasing in Japan and other countries. Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn (JIMRO, Takasaki, Japan) was introduced as a nonpharmacologic treatment strategy in UC patients in 2000. GMA has been reported to be effective in clinical trials; however, the effect of concomitant prednisolone (PSL) on GMA needs to be clarified. Methods: Thirty-nine patients with active UC were treated with GMA at our institute between June 2009 and September 2018. All patients received GMA therapy once or twice a week with the Adacolumn. Conventional medication was to be continued during the whole GMA treatment course. The clinical response was retrospectively evaluated. Results: According to the partial Mayo score, remission was 33.3%, significant efficacy 25.6%, effective 25.6%, and no response 15.4%. The average partial Mayo score was 6.2 ± 1.4 at entry and significantly declined to 1.8 ± 1.8 after GMA sessions ( p < 0.0001). The average number of bowel movements was 9.5 ± 5.6 at entry and significantly declined to 3.0 ± 2.8 after GMA sessions ( p < 0.0001). In a comparison between the group treated with concomitant PSL and the group without PSL, the change in partial Mayo score or the number of bowel movements from entry to after GMA sessions was not significantly different. Among 24 patients treated by GMA with concomitant PSL, 75% (18/24) became steroid free. Conclusions: The effect of GMA with concomitant PSL and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

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

Abbi R Saniabadi, Tomotaka Tanaka, Toshihide Ohmori … (2014)

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 21st 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.

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Colonoscopic evaluation in ulcerative colitis

Elizabeth Paine (2014)

Colonoscopic evaluation is an important tool in the evaluation of ulcerative colitis (UC). UC is divided by disease extent into proctitis, proctosigmoiditis, left-sided colitis, and pan-colitis. In addition, a cecal or peri-appendiceal patch and backwash ileitis are associated with UC. The extent and behavior of UC has been characterized further using various indices and scoring systems; among these systems is the Mayo Score, which is widely used in current clinical trials for new medications. As these medical therapies for UC have developed, achieving mucosal healing with medications has become an important therapeutic objective.

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Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study.

Yasushi Saito, Naoki Yoshimura, Abby Saniabadi … (2004)

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.

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Author and article information

Journal

Journal ID (publisher-id): IID

Journal ID (pmc): IID

Journal ID (doi): 10.1159/issn.2296-9365

Title: Inflammatory Intestinal Diseases

Publisher: S. Karger AG

ISSN (Print): 2296-9403

ISSN (Electronic): 2296-9365

Publication date Subscription-year: 2020

Publication date (Print): February 2020

Publication date (Electronic): 28 January 2020

Volume: 5

Issue: 1

Pages: 36-41

Affiliations

[_a] _aDepartment of Surgery, Teikyo University School of Medicine, Tokyo, Japan

[_b] _bIBD Center, Teikyo University School of Medicine, Tokyo, Japan

[_c] _cDepartment of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan

[_d] _dDepartment of Renal Center, Teikyo University School of Medicine, Tokyo, Japan

[_e] _eDepartment of Pathology, Teikyo University School of Medicine, Tokyo, Japan

Author notes

*Keiji Matsuda, MD, PhD, Department of Surgery, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605 (Japan), E-Mail keiji@med.teikyo-u.ac.jp

Article

Publisher ID: 505484 Other ID: Inflamm Intest Dis 2020;5:36–41

DOI: 10.1159/000505484

PubMed ID: 32232053

SO-VID: eb40d038-d8a4-48fb-8e24-74abe1c0ef71

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This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 18 May 2019

Date accepted : 16 December 2019

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Figures: 5, Tables: 2, Pages: 6

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Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone

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Karger: Gastroenterology

Most cited references 9

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

Colonoscopic evaluation in ulcerative colitis

Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naïve patients with active ulcerative colitis: a prospective uncontrolled study.

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