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Fernández-Pérez FJ, Fernández-Moreno N, Soria-López E, Rodriguez-González FJ, Fernández-Galeote FJ, Lifante-Oliva A, Ruíz-Hernández C, Escalante-Quijaite E, Rivas-Ruiz F. Granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease: A useful therapeutic tool not just in ulcerative colitis but also in Crohn's disease. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:502196. [PMID: 38710467 DOI: 10.1016/j.gastrohep.2024.502196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2023] [Revised: 01/27/2024] [Accepted: 02/14/2024] [Indexed: 05/08/2024]
Abstract
INTRODUCTION Granulocyte and monocyte adsorptive apheresis (GMA) removes neutrophils and monocytes from peripheral blood, preventing their incorporation into the inflamed tissue also influencing cytokine balance. Published therapeutic efficacy in ulcerative colitis (UC) is more consistent than in Crohn's disease (CD). We assessed clinical efficacy of GMA in UC and CD 4 weeks after last induction session, at 3 and 12 months, sustained remission and corticosteroid-free remission. PATIENTS AND METHOD Retrospective observational study of UC and CD patients treated with GMA. Partial Disease Activity Index-DAIp in UC and Harvey-Bradshaw Index-HBI in CD assessed efficacy of Adacolumn® with induction and optional maintenance sessions. RESULTS We treated 87 patients (CD-25, UC-62), 87.3% corticosteroid-dependent (CSD), 42.5% refractory/intolerant to immunomodulators. In UC, remission and response were 32.2% and 19.3% after induction, 35.5% and 6.5% at 12 weeks and 29% and 6.5% at 52 weeks. In CD, remission rates were 60%, 52% and 40% respectively. In corticosteroid-dependent and refractory or intolerant to INM patients (UC-41, CD-14), 68.3% of UC achieved remission or response after induction, 51.2% at 12 weeks and 46.3% at 52 weeks, and 62.3%, 64.3% and 42.9% in CD. Maintained remission was achieved by 66.6% in CD and 53.1% in UC. Up to 74.5% of patients required corticosteroids at some timepoint. Corticosteroid-free response/remission was 17.7% in UC and 24% in CD. CONCLUSIONS GMA is a good therapeutic tool for both in UC and CD patients. In corticosteroid-dependent and refractory or intolerant to INM patients it avoids biological therapy or surgery in up to 40% of them in one year.
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Vernia F, Viscido A, Latella G. Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited. J Clin Apher 2023; 38:746-754. [PMID: 37787399 DOI: 10.1002/jca.22091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/03/2023] [Accepted: 09/14/2023] [Indexed: 10/04/2023]
Abstract
Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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Furuto Y, Sawada R, Namikawa A, Matsuhashi N, Shibuya Y. Intensive Frequent Granulocyte Adsorptive Apheresis Therapy for Acute Fulminant Ulcerative Colitis: Two Consecutive Case Reports. Cureus 2023; 15:e43599. [PMID: 37719478 PMCID: PMC10503873 DOI: 10.7759/cureus.43599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/16/2023] [Indexed: 09/19/2023] Open
Abstract
Granulocyte/monocyte adsorptive apheresis (GMA) therapy is a treatment method for ulcerative colitis (UC). Twice-weekly GMA regimens are usually administered to treat severe UC. Although GMA efficacy is considered frequency-dependent, there is no uniformly accepted optimal GMA regimen, and there is insufficient evidence regarding optimal GMA therapy frequency for acute fulminant UC. Case 1 was of a 33-year-old man, and case 2 was of a 20-year-old woman. They were diagnosed with acute fulminant UC and treated with steroid therapy, but exhibited exacerbated UC, and their conditions worsened. We, therefore, initiated intensive frequent GMA therapy (conducted 10-11 times during a 13-day period). In both cases, remission was achieved within two weeks of therapy induction. Herein, we describe two consecutive cases in which rapid remission of acute fulminant UC was achieved without adverse events using intensive frequent GMA therapy. These cases suggest that intensive frequent GMA therapy might induce rapid remission in acute fulminant UC cases and may be more effective than twice-weekly GMA regimens.
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Affiliation(s)
- Yoshitaka Furuto
- Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, Tokyo, JPN
| | - Rikimaru Sawada
- Department of Gastrointestinal Endoscopy, NTT Medical Centre Tokyo, Tokyo, JPN
| | - Akio Namikawa
- Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, Tokyo, JPN
| | - Nobuyuki Matsuhashi
- Department of Gastrointestinal Endoscopy, NTT Medical Centre Tokyo, Tokyo, JPN
| | - Yuko Shibuya
- Department of Hypertension and Nephrology, NTT Medical Centre Tokyo, Tokyo, JPN
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Yasmin F, Najeeb H, Naeem U, Moeed A, Koritala T, Surani S. Apheresis: A cell-based therapeutic tool for the inflammatory bowel disease. World J Clin Cases 2022; 10:7195-7208. [PMID: 36158031 PMCID: PMC9353887 DOI: 10.12998/wjcc.v10.i21.7195] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 12/16/2021] [Accepted: 06/04/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) is a hallmark of leukocyte infiltration, followed by the release of cytokines and interleukins. Disease progression to Ulcerative Colitis (UC) or Crohn's Disease (CD) remained largely incurable. The genetic and environmental factors disrupt enteral bacteria in the gut, which hampers the intestinal repairing capability of damaged mucosa. Commonly practiced pharmacological therapies include 5-aminosalicylic acid with corticosteroids and tumor necrosis factor (TNF)-α. New interventions such as CDP571 and TNF-blocking RDP58 report the loss of patient response. This review discusses the non-pharmacologic selective granulocyte-monocyte-apheresis (GMA) and leukocytapheresis (LCAP) that have been proposed as treatment modalities that reduce mortality. GMA, an extracorporeal vein-to-vein technique, presents a strong safety profile case for its use as a viable therapeutic option compared to GMA's conventional medication safety profile. GMA reported minimal to no side effects in the pediatric population and pregnant women. Numerous studies report the efficacious nature of GMA in UC patients, whereas data on CD patients is insufficient. Its benefits outweigh the risks and are emerging as a favored non-pharmacological treatment option. On the contrary, LCAP uses a general extracorporeal treatment that entraps leukocytes and suppresses cytokine release. It has been deemed more efficacious than conventional drug treatments, the former causing better disease remission, and maintenance. Patients with UC/CD secondary to complications have responded well to the treatment. Side effects of the procedure have remained mild to moderate, and there is little evidence of any severe adverse event occurring in most age groups. LCAP decreases the dependence on steroids and immunosuppressive therapies for IBD. The review will discuss the role of GMA and LCAP.
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Affiliation(s)
- Farah Yasmin
- Department of Medicine, DOW University of Health Sciences, Karachi 74200, Pakistan
| | - Hala Najeeb
- Department of Medicine, DOW University of Health Sciences, Karachi 74200, Pakistan
| | - Unaiza Naeem
- Department of Medicine, DOW University of Health Sciences, Karachi 74200, Pakistan
| | - Abdul Moeed
- Department of Medicine, DOW University of Health Sciences, Karachi 74200, Pakistan
| | - Thoyaja Koritala
- Department of Medicine, Mayo Clinic, Rochester, MN 55902, United States
| | - Salim Surani
- Department of Medicine, Texas A&M University, College Station, Texas 77843, United States
- Department of Anaesthesiology, Mayo Clinic, Rochester, MN 55902, United States
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Golsorkhi M, Azarfar A, Abdipour A. Vascular Access in Therapeutic Apheresis: One Size Does not Fit All. Ther Apher Dial 2022; 26:694-716. [PMID: 35043567 DOI: 10.1111/1744-9987.13799] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/19/2021] [Accepted: 01/13/2022] [Indexed: 11/27/2022]
Abstract
BACKGROUND Therapeutic apheresis has been used in treating hematological and non-hematological diseases. For a successful procedure, efficient vascular access is required. Presently, peripheral venous access (PVA), central venous catheterization (CVC), implantable ports, and arteriovenous fistulas (AVFs) are used. This review aims to evaluate different type of access and their pros and cons to help physicians determine the best venous access. METHODS The electronic search included PubMed and Google Scholar up to Nov. 2020. The Mesh terms were apheresis, peripheral catheterization, central catheterization, and arteriovenous fistula. RESULTS A total of 228 studies were found through database searching. Two independent authors reviewed the articles using their titles and abstracts; 88 articles were selected and the full text was reviewed. Finally, 25 were included. The inclusion criteria were studies incorporating patients with any indication for apheresis. CONCLUSION PVA has been promoted in recent years in many centers across the United States to lower the rate of complications associated with vascular access and to make this procedure more accessible. Several factors are involved in selecting appropriate venous access, such as the procedure's duration and frequency, patient's vascular anatomy, and staff's experience. In short-term procedures, temporary vascular access like PVA or CVC is preferred. Permanent vascular access such as AVF, tunneled cuffed central lines, and implantable ports are more beneficial in prolonged treatment period but each patient has to be evaluated individually by apheresis team for the most appropriate method.
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Affiliation(s)
- Mohadese Golsorkhi
- Department of Medicine, Division of Regenerative Medicine, Loma Linda University, Loma Linda, CA, USA
| | - Anoush Azarfar
- Kidney Transplantation Complications Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Abdipour
- Department of Medicine, Division of Nephrology, Loma Linda University, Loma Linda, CA, USA
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Kiss S, Németh D, Hegyi P, Földi M, Szakács Z, Erőss B, Tinusz B, Hegyi PJ, Sarlós P, Alizadeh H. Granulocyte and monocyte apheresis as an adjunctive therapy to induce and maintain clinical remission in ulcerative colitis: a systematic review and meta-analysis. BMJ Open 2021; 11:e042374. [PMID: 34011580 PMCID: PMC8137160 DOI: 10.1136/bmjopen-2020-042374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Revised: 03/31/2021] [Accepted: 04/11/2021] [Indexed: 01/09/2023] Open
Abstract
OBJECTIVE The goal of treatment in ulcerative colitis (UC) is to induce and maintain remission. The addition of granulocyte and monocyte apheresis (GMA) to conventional therapy may be a promising therapeutic alternative. In this meta-analysis, we aimed to assess the efficacy and safety profile of GMA as an adjunctive therapy. DESIGN Systematic review and meta-analysis. METHODS We searched four databases (MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials) for randomised or minimised controlled trials which discussed the impact of additional GMA therapy on clinical remission induction and clinical remission maintenance compared with conventional therapy alone. Primary outcomes were clinical remission induction and maintenance, secondary outcomes were adverse events (AEs) and steroid-sparing effect. ORs with 95% CIs were calculated. Trial Sequential Analyses were performed to adjusts for the risk of random errors in meta-analyses. RESULTS A total of 11 studies were eligible for meta-analysis. GMA was clearly demonstrated to induce and maintain clinical remission more effectively than conventional therapy alone (598 patients: OR: 1.93, 95% CI 1.28 to 2.91, p=0.002, I2=0.0% for induction; 71 patients: OR: 8.34, 95% CI 2.64 to 26.32, p<0.001, I2=0.0% for maintenance). There was no statistically significant difference in the number of AEs (OR: 0.27, 95% CI 0.05 to 1.50, p=0.135, I2=84.2%). CONCLUSION GMA appears to be more effective as an adjunctive treatment in inducing and maintaining remission in patients with UC than conventional therapy alone. PROSPERO REGISTRATION NUMBER CRD42019134050.
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Affiliation(s)
- Szabolcs Kiss
- Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Dávid Németh
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Péter Hegyi
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Mária Földi
- Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Zsolt Szakács
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
- Division of Haematology, First Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Bálint Erőss
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- János Szentágothai Research Centre, University of Pécs, Pécs, Hungary
| | - Benedek Tinusz
- Division of Geriatric Medicine, First Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Péter Jenő Hegyi
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- Division of Gastroenterology, First Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Patrícia Sarlós
- Institute for Translational Medicine, University of Pécs Medical School, Pécs, Hungary
- Division of Gastroenterology, First Department of Medicine, University of Pécs Medical School, Pécs, Hungary
| | - Hussain Alizadeh
- Doctoral School of Clinical Medicine, University of Szeged, Szeged, Hungary
- Division of Haematology, First Department of Medicine, University of Pécs Medical School, Pécs, Hungary
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Chen X, Lou L, Tang H, Tan X, Bi J, Wu H, Li N, Wang Y, Mao J. Adsorptive granulomonocytapheresis alters the gut bacterial microbiota in patients with active ulcerative colitis. J Clin Apher 2021; 36:454-464. [PMID: 33598970 DOI: 10.1002/jca.21887] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/18/2021] [Accepted: 02/05/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Ulcerative colitis (UC) is a refractory disease with unclear etiology. Studies have shown that UC is closely associated with gut microbiota dysbiosis. Adsorptive granulomonocytapheresis (GMA) using an Adacolumn has been found to treat UC effectively, but its underlying mechanism of treatment has not been fully elucidated. In this study, we aimed to investigate the influence of GMA on the gut microbiota in patients with active UC. METHODS We conducted a single-center prospective analysis of patients with active UC who received GMA therapy and ultimately achieved clinical remission. Stool samples of healthy controls and patients before and after 5 or 10 sessions of GMA therapy were collected. Subsequently, high-throughput sequencing of the 16S rRNA V3 and V4 gene region of the stool was conducted and clustering of operational taxonomic units and species annotation were performed. RESULTS Gut microbial profiles in patients with UC were characterized by low bacterial diversity. After 5 or 10 sessions of GMA therapy, the gut microbiota diversity in patients with UC increased and was similar to that of healthy controls. UC was further characterized by increased abundances of Proteobacteria and Bacteroides, as well as decreased abundances of Faecalibacterium, Roseburia, Firmicutes, and Dialister; however, after GMA therapy, the abundance of Bacteroides decreased, whereas those of Faecalibacterium, Roseburia, and Firmicutes increased. CONCLUSIONS Active UC is associated with gut microbiota dysbiosis. GMA therapy exerts a strong regulatory effect on the gut microbiota in patients with UC.
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Affiliation(s)
- Xiuli Chen
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Lian Lou
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.,Department of Gastroenterology, 967 Hospital of the Joint Logistics Support Force of PLA, Dalian, Liaoning, China
| | - Haiying Tang
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Xiaoyan Tan
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Jian Bi
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Hao Wu
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Na Li
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Yingde Wang
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
| | - Jingwei Mao
- Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China
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Kakimoto K, Matsuura M, Fukuchi T, Hongo H, Kimura T, Aoyama N, Okuda Y, Aomatsu K, Kamata N, Yokoyama Y, Mizuno C, Inoue T, Miyazaki T, Nakamura S, Higuchi K, Nakase H. Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial. CROHNS & COLITIS 360 2020; 2:otaa073. [PMID: 34192247 PMCID: PMC7797742 DOI: 10.1093/crocol/otaa073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Indexed: 12/20/2022]
Abstract
Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid. EXPECT study demonstrates that granulocyte and monocyte adsorptive apheresis has promising effectiveness with regard to inducing remission in patients with active ulcerative colitis (UC) who are not receiving steroid treatment. The first episode of UC was an independent predictor of a response in multiple logistic regression.
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Affiliation(s)
- Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Takumi Fukuchi
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Osaka, Japan
| | - Hitoshi Hongo
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Tsuguhiro Kimura
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Nobuo Aoyama
- Department of Gastroenterology, Gastrointestinal Endoscopy and IBD Center, Aoyama Medical Clinic, Kobe, Hyogo, Japan
| | - Yorihide Okuda
- Department of Gastroenterology, Otemae Hospital, Osaka, Osaka, Japan
| | - Kazuki Aomatsu
- Department of Gastroenterology, Izumiotsu Municipal Hospital, Izumiotsu, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Yoko Yokoyama
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Takuya Inoue
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Takako Miyazaki
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Shiro Nakamura
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Kazuhide Higuchi
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
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Mezzina N, Campbell Davies SE, Ardizzone S. Nonbiological therapeutic management of ulcerative colitis. Expert Opin Pharmacother 2018; 19:1747-1757. [DOI: 10.1080/14656566.2018.1525361] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Affiliation(s)
- Nicolò Mezzina
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco – Department of Biochemical and Clinical Sciences “L. Sacco”, University of Milan, Milano, Italy
| | | | - Sandro Ardizzone
- Gastrointestinal Unit, ASST Fatebenefratelli Sacco – Department of Biochemical and Clinical Sciences “L. Sacco”, University of Milan, Milano, Italy
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Dignass A, Akbar A, Baumgart DC, Bommelaer G, Bouguen G, Cadiot G, Gillessen A, Grimaud JC, Hart A, Hoque S, Makins R, Michiels C, Moreau J, Premchand P, Ramlow W, Schanz S, Subramanian S, von Tirpitz C, Bonaz B. Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis. Scand J Gastroenterol 2018. [PMID: 29513111 DOI: 10.1080/00365521.2018.1447598] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn®) in this population. MATERIALS AND METHODS Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5-8 aphereses in a single induction series of ≤10 weeks. Endpoints included rates of remission (clinical activity index [CAI] ≤ 4) at weeks 24 and 48. RESULTS Of 94 patients (ITT population), remission and response rates were 34.0% and 44.7% at week 24, and 33.0% and 39.4% at week 48. Among 30 patients with prior failure of IS and biologics, 33.3% and 20.0% were in remission at weeks 24 and 48. At both weeks, 19.2% of patients achieved steroid-free remission. Sustained remission or response occurred in 27.7% of patients at 48 weeks. The cumulative colectomy rate at week 96 was 23.4%. Safety was consistent with previous findings. CONCLUSIONS This study confirms findings of the 12-week interim analysis and demonstrates that GMA apheresis provides a safe and beneficial long-term outcome for patients with chronic active UC resistant/intolerant to IS and/or TNF inhibitors.
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Affiliation(s)
- Axel Dignass
- a Department of Gastroenterology, Hepatology, Oncology and Metabolic Diseases , Markus-Krankenhaus , Frankfurt/Main , Germany
| | - Ayesha Akbar
- b IBD Unit, St. Mark's Hospital and Academic Institute , London , UK
| | - Daniel C Baumgart
- c Department of Medicine, Division of Gastroenterology and Hepatology , Charité Medical Center - Virchow Hospital, Medical School of the Humboldt-University of Berlin , Berlin , Germany
| | - Gilles Bommelaer
- d Service Hépatologie-Gastroentérologie, CHU Clermont-Ferrand , Clermont-Ferrand , France
| | - Guillaume Bouguen
- e Service des Maladies de l'Appareil Digestif et CIC1414, University Hospital of Rennes , Pontchaillou , France
| | - Guillaume Cadiot
- f Service d'Hépato-gastro-entérologie, CHU du Reims, Hôpital Robert Debré , Reims Cedex , France
| | | | | | - Ailsa Hart
- b IBD Unit, St. Mark's Hospital and Academic Institute , London , UK
| | - Syed Hoque
- i Barts Health NHS Trust, Whipps Cross University Hospital , London , UK
| | | | | | | | | | - Wolfgang Ramlow
- n Clinic for Nephrology, Dialysis and Apheresis , Rostock , Germany
| | | | - Sreedhar Subramanian
- p Department of Gastroenterology , Royal Liverpool University Hospital , Liverpool , UK
| | | | - Bruno Bonaz
- r Clinique Universitaire d'Hépato-Gastroentérologie, CHU Grenoble , Grenoble , France
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11
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Granulocyte-Monocyte Apheresis in Steroid-Dependent, Azathioprine-Intolerant/Resistant Moderate Ulcerative Colitis: A Prospective Multicenter Study. Gastroenterol Res Pract 2017; 2017:9728324. [PMID: 29403531 PMCID: PMC5748298 DOI: 10.1155/2017/9728324] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2017] [Revised: 04/03/2017] [Accepted: 05/15/2017] [Indexed: 12/18/2022] Open
Abstract
Background Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. Aim To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. Methods Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. Results From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36%) patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9%) cases showed a clinical response (but not clinical remission). Moreover, 12 (36%) patients required biologic therapy, 4 (12%) underwent colectomy, and in the other 2 (6%) a reduction, but not withdrawal, of steroid dose was achieved. Conclusions Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.
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Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease. Dig Dis Sci 2017; 62:1417-1425. [PMID: 28432476 DOI: 10.1007/s10620-017-4577-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 04/08/2017] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). The study of immunological pathways involved in the onset of IBD is of fundamental importance to identify potential biological markers of disease activity and specific targets for therapy. Removing excess and activated circulating leukocytes with adsorptive cytapheresis has been shown to be a potentially effective treatment for patients with an inflamed bowel. Adsorptive cytapheresis is a non-pharmacological approach for active IBD, in which known sources of inflammatory cytokines such as activated myeloid lineage leucocytes are selectively depleted from the circulatory system. The decrease in inflammatory load caused by removing these cells is thought to enhance drug therapy and thereby promote disease remission. The benefit of cytapheresis appears to rest upon its ability to reduce levels of certain immune cell populations; however, whether this depletion results in further changes in lymphocyte populations and cytokine production needs further clarification. In this review, we aim to summarize existing evidence on the role of cytapheresis in patients with IBD, its effect on cytokine levels and cellular populations, and to discuss its potential impact on disease activity.
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Dignass A, Akbar A, Hart A, Subramanian S, Bommelaer G, Baumgart DC, Grimaud JC, Cadiot G, Makins R, Hoque S, Bouguen G, Bonaz B. Safety and Efficacy of Granulocyte/Monocyte Apheresis in Steroid-Dependent Active Ulcerative Colitis with Insufficient Response or Intolerance to Immunosuppressants and/or Biologics [the ART Trial]: 12-week Interim Results. J Crohns Colitis 2016; 10:812-20. [PMID: 26818659 PMCID: PMC4955912 DOI: 10.1093/ecco-jcc/jjw032] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Accepted: 01/19/2016] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND AIMS Patients with active, steroid-dependent ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologic therapies have limited treatment options. Adacolumn, a granulocyte/monocyte adsorptive apheresis device, has shown clinical benefit in these patients. This study aimed to provide additional clinical data regarding the safety and efficacy of Adacolumn in this patient subgroup. METHODS This single-arm, open-label, multicentre trial [ART] was conducted at 18 centres across the UK, France, and Germany. Eligible patients were 18-75 years old with moderate-to-severe, steroid-dependent active ulcerative colitis with insufficient response or intolerance to immunosuppressants and/or biologics. Patients received ≥ 5 weekly apheresis sessions with Adacolumn. The primary endpoint was clinical remission rate [clinical activity index ≤ 4] at Week 12. RESULTS In all, 86 patients were enrolled. At Week 12, 33/84 [39.3%] of patients in the intention-to-treat population achieved clinical remission, with 47/84 [56.0%] achieving a clinical response [clinical activity index reduction of ≥ 3]. Clinical remission was achieved in 30.0% of patients with previous immunosuppressant and biologic failure; steroid-free clinical remission and response were observed in 22.6% and 35.7% of these patients, respectively. Quality of life [Short Health Scale] significantly improved at Week 12 [p < 0.0001]. The majority of adverse events were of mild/moderate intensity. CONCLUSIONS At Week 12, Adacolumn provided significant clinical benefit in a large cohort of steroid-dependent ulcerative colitis patients with previous failure to immunosuppressant and/or biologic treatment, with a favourable safety profile. These results are consistent with previous studies and support Adacolumn use in this difficult-to-treat patient subgroup.
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Affiliation(s)
- Axel Dignass
- Department of Gastroenterology, Hepatology, Oncology and Metabolic Diseases, Markus-Krankenhaus, Frankfurt/Main, Germany
| | - Ayesha Akbar
- IBD Unit, St Mark’s Hospital and Academic Institute, London, UK
| | - Ailsa Hart
- IBD Unit, St Mark’s Hospital and Academic Institute, London, UK
| | - Sreedhar Subramanian
- Department of Gastroenterology, Royal Liverpool University Hospital, Liverpool, UK
| | - Gilles Bommelaer
- Service Hépatologie-Gastroentérologie, CHU Clermont-Ferrand, Clermont-Ferrand, France
| | - Daniel C. Baumgart
- Department of Medicine, Division of Gastroenterology and Hepatology, Charité Medical Center - Virchow Hospital, Humboldt-University of Berlin, Germany
| | | | - Guillaume Cadiot
- Service d’Hépato-gastro-entérologie, CHU du Reims, Hôpital Robert Debré, Reims, France
| | | | - Syed Hoque
- Barts Health NHS Trust, Whipps Cross University Hospital, London, UK
| | - Guillaume Bouguen
- Service des Maladies de l’Appareil Digestif et CIC1414, University Hospital of Rennes, Pontchaillou, France
| | - Bruno Bonaz
- Clinique Universitaire d’Hépato-Gastroentérologie, CHU Grenoble, Grenoble, France
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Ruuska T, Küster P, Grahnquist L, Lindgren F, Wewer AV. Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis. World J Gastroenterol 2016; 22:4389-4396. [PMID: 27158208 PMCID: PMC4853697 DOI: 10.3748/wjg.v22.i17.4389] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2015] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis.
METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn® granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint was the change in mean PUCAI between baseline and week 12; the secondary endpoint was improvement in PUCAI categorized as (Significant Improvement, PUCAI decrease of ≥ 35), Moderate Improvement (PUCAI decrease of 20 < 35), Small Improvement (PUCAI decrease of 10 < 20) or No change (PUCAI decrease of < 10).
RESULTS: Twenty-five patients (mean age 13.5 years; mean weight 47.7 kg) were enrolled. In the intention-to-treat set (ITT), the mean value for PUCAI improvement was 22.3 [95%CI: 12.9-31.6; n = 21]. In the per-protocol (PP) set, the mean improvement was 36.3 [95%CI: 31.4-41.1; n = 8]. Significant Improvement was recorded for 9 out of 20 patients (45%); 5 out of 20 patients (25%) had Moderate Improvement and one patient (5%) had No Change in PUCAI score at week 12. In the PP set, six out of eight patients (75%) showed Significant Improvement; and in two out of eight patients (25%) Moderate Improvement was recorded. The endoscopic activity index (EAI) decreased by 3 points on average. Seven (7) out of 21 (33%) patients in ITT and 4 out of 8 (50%) patients in PP have used steroids during the clinical investigation. The mean steroid dosage for these patients in the ITT set decreased from a mean 12.4 mg to 10 mg daily on average from Baseline to week 12.
CONCLUSION: Adacolumn® GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option in pediatric patients having failed first line therapy.
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Saito H, Hanafusa N, Kishikawa J, Noiri E, Sunami E, Ishihara S, Watanabe T, Nangaku M. Ulcerative colitis with hepatitis B virus infection treated successfully by granulocyte monocyte apheresis. J Clin Apher 2016; 31:584-586. [PMID: 26876484 DOI: 10.1002/jca.21450] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Revised: 01/19/2016] [Accepted: 01/20/2016] [Indexed: 01/24/2023]
Abstract
Ulcerative colitis (UC) is a major type of idiopathic inflammatory bowel disease (IBD). Immunosuppressive therapies are used to treat IBD patients. Clinicians have strong concerns about using immunosuppressive therapies for IBD patients with hepatitis B virus (HBV) infection because aggressive immunosuppressive therapy can promote reactivation of HBV. For that reason, physicians hesitate to use steroids or other immunosuppressive drugs for IBD patients with HBV infection. Granulocyte monocyte apheresis (GMA) is a safe and effective therapy for UC patients. In Japan, a maximum of 11 sessions of GMA are allowed for moderate-to-severe, steroid-resistant UC patients. However, the effects of GMA on HBV remain unclear. This case report describes a 39-year-old man with active UC complicated by HBV infection. Although his symptoms improved with steroid treatment while under entecavir therapy, clinical remission could not be maintained after the steroid dosage was decreased, so GMA was started. After GMA initiation, the frequency of diarrhea decreased and his symptoms improved, and the steroid dosage could be decreased. During the course of GMA, the patient did not experience deterioration in his hepatitis and the HBV DNA level gradually decreased, although GMA itself did not affect the HBV DNA level during each session of GMA. Results show that GMA is a safe and efficacious strategy against UC complicated by HBV without affecting hepatitis because GMA had no remarkable effect on HBV activity. J. Clin. Apheresis 31:584-586, 2016. © 2015 Wiley Periodicals, Inc.
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Affiliation(s)
- Hisako Saito
- Department of Hemodialysis and Apheresis, the University of Tokyo Hospital, Tokyo, Japan
| | - Norio Hanafusa
- Department of Hemodialysis and Apheresis, the University of Tokyo Hospital, Tokyo, Japan
| | - Junko Kishikawa
- Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, Tokyo, Japan
| | - Eisei Noiri
- Department of Hemodialysis and Apheresis, the University of Tokyo Hospital, Tokyo, Japan
| | - Eiji Sunami
- Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, Tokyo, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, Tokyo, Japan
| | - Toshiaki Watanabe
- Department of Surgical Oncology, Faculty of Medical Sciences, the University of Tokyo, Tokyo, Japan
| | - Masaomi Nangaku
- Department of Hemodialysis and Apheresis, the University of Tokyo Hospital, Tokyo, Japan
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Edfors K, Ståhlberg D, Söderman C. Retrospective Single Center Study of Granulocyte Monocyte Adsorption Apheresis Treatment in Inflammatory Bowel Disease. Ther Apher Dial 2016; 20:79-85. [PMID: 26841133 DOI: 10.1111/1744-9987.12336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2014] [Revised: 05/03/2015] [Accepted: 06/08/2015] [Indexed: 01/17/2023]
Abstract
Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leukocytes, which infiltrate the intestinal mucosa. A significant proportion of IBD patients do not respond adequately to conventional treatment regimes. Studies have suggested that treatment with granulocyte monocyte apheresis (GMA) could be a safe and efficacious alternative for these patients. We evaluated the efficacy and safety of granulocyte/monocyte apheresis in patients with IBD in a retrospective cohort study, conducted from a single center in Stockholm. Clinical details from consecutive apheresis treated patients were retrospectively reviewed from 2004 to 2012. A total of 37 patients were included, 23 patients with ulcerative colitis (UC) and 14 with Crohn's disease (CD). Clinical response was seen in 11 patients (30%) and complete remission in 11 patients (30%). The remission rate was higher in UC patients compared to CD patients, 39% (N = 9) and 14% (N = 2) respectively. A total of 9 patients experienced adverse events. Most frequently reported was headache (N = 4). GMA seems to be a valuable adjuvant treatment regime in the care of patients with refractory IBD.
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Affiliation(s)
- Kajsa Edfors
- Gastroenterology Unit, Department of Medicine, Capio St. Goran Hospital, Stockholm, Sweden
| | - Dagny Ståhlberg
- Gastroenterology Unit, Department of Medicine, Capio St. Goran Hospital, Stockholm, Sweden
| | - Charlotte Söderman
- Gastroenterology Unit, Department of Medicine, Capio St. Goran Hospital, Stockholm, Sweden
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Hashiguchi K, Takeshima F, Akazawa Y, Matsushima K, Minami H, Machida H, Yamaguchi N, Shiozawa K, Ohba K, Ohnita K, Ichikawa T, Isomoto H, Nakao K. Advantages of fecal lactoferrin measurement during granulocyte and monocyte adsorptive apheresis therapy in ulcerative colitis. Digestion 2015; 91:208-17. [PMID: 25823500 DOI: 10.1159/000375301] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2014] [Accepted: 01/16/2015] [Indexed: 02/04/2023]
Abstract
BACKGROUND Fecal lactoferrin has been introduced as a useful tool for the diagnosis and monitoring of inflammatory bowel disease (IBD). The aim of this study was to assess if fecal lactoferrin can be employed to predict or estimate the effect of granulocyte and monocyte adsorptive apheresis (GMA) in ulcerative colitis (UC). METHODS This was a prospective study involving 21 patients with UC. Patients with moderately-to-severely active UC who were scheduled to undergo GMA were recruited. Changes in fecal lactoferrin concentration were compared between the GMA-responder and -nonresponder groups. RESULTS In the GMA-responder group, fecal lactoferrin significantly increased 1 week after the introduction of GMA and then significantly decreased after GMA sessions. Fecal lactoferrin concentrations were significantly higher in the GMA-responder group than in the GMA-nonresponder group at 1 and 2 weeks after the introduction of GMA. Multivariate logistic regression analysis revealed that fecal lactoferrin concentration 1 week after the introduction of GMA was the most contributing factor for the effectiveness of GMA in patients with UC. CONCLUSIONS In the GMA-responder group, fecal lactoferrin concentration significantly increased 1 week after the introduction of GMA. Fecal lactoferrin may be beneficial for predicting clinical response of GMA in patients with UC at an early stage of GMA treatment.
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Affiliation(s)
- Keiichi Hashiguchi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
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Sacco R, Tanaka T, Yamamoto T, Bresci G, Saniabadi AR. Adacolumn leucocytapheresis for ulcerative colitis: clinical and endoscopic features of responders and unresponders. Expert Rev Gastroenterol Hepatol 2015; 9:327-33. [PMID: 25160857 DOI: 10.1586/17474124.2014.953060] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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.
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Affiliation(s)
- Rodolfo Sacco
- Department of Gastroenterology-Pisa University Hospital, Pisa, Italy
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19
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De Cassan C, Savarino E, Marson P, Tison T, Hatem G, Sturniolo GC, D’Incà R. Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease. World J Gastroenterol 2014; 20:17155-17162. [PMID: 25493030 PMCID: PMC4258586 DOI: 10.3748/wjg.v20.i45.17155] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2014] [Revised: 05/17/2014] [Accepted: 06/26/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity.
METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients’ charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points.
RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively).
CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics.
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20
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Olsen HH, Muratov V, Cederlund K, Lundahl J, Eklund A, Grunewald J. Therapeutic granulocyte and monocyte apheresis (GMA) for treatment refractory sarcoidosis: a pilot study of clinical effects and possible mechanisms of action. Clin Exp Immunol 2014; 177:712-9. [PMID: 24773420 DOI: 10.1111/cei.12360] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/17/2014] [Indexed: 12/27/2022] Open
Abstract
Sarcoidosis is a systemic, inflammatory disorder, which in a proportion of patients runs a chronic progressive course despite immunosuppressive treatment. Therapeutic granulocyte and monocyte apheresis (GMA) has been shown to be an effective treatment option for other systemic inflammatory disorders, but has not yet been investigated in sarcoidosis. The aim of this study was to evaluate the response to GMA in sarcoidosis. Seven patients with sarcoidosis refractory to standard immunosuppressive therapy received 10 GMA sessions. All patients underwent chest X-ray, spirometry, a Chronic Respiratory Disease Questionnaire (CRQ-SAS), blood tests and bronchoscopy with bronchoalveolar lavage (BAL) before treatment and at 2-4 weeks and 3 months (except bronchoscopy) after the last treatment session. Bronchoalveolar lavage fluid (BALF) cell differential counts were recorded and T cells from blood and BALF were analysed for markers of activity, differentiation and T regulatory function. Compared to baseline, five of seven patients reported an improvement in dyspnoea score. In BALF there was an increase in the percentage of macrophages and a decrease in the percentage of lymphocytes and CD4(+) /FoxP3(+) T cells. Furthermore, the decrease in BALF CD4(+) /FoxP3(+) T cells correlated significantly with an improvement in dyspnoea score. In peripheral blood there was a statistically significant increase in the percentage of CD4(+) /CD27(-) T cells and a trend towards an initial increase in the percentage of CD4(+) /FoxP3(+) T cells, followed by a statistically significant decrease. The effects of GMA on regulatory T cells are consistent with those observed in other inflammatory disorders and could potentially translate into a clinical benefit.
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Affiliation(s)
- H H Olsen
- Respiratory Medicine Unit, Department of Medicine and CMM, Karolinska Institutet and Karolinska University Hospital, Solna, Sweden
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D'Ovidio V, Meo D, Gozer M, Bazuro ME, Vernia P. Ulcerative colitis and granulocyte-monocyte-apheresis: safety and efficacy of maintenance therapy during pregnancy. J Clin Apher 2014; 30:55-7. [PMID: 25181523 DOI: 10.1002/jca.21349] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2013] [Revised: 06/30/2014] [Accepted: 07/11/2014] [Indexed: 12/24/2022]
Abstract
Inflammatory bowel disease characteristically affects young adults in their reproductive ages. Thus the medication used for the treatment of active disease should not compromise fertility and, also, should not have teratogenic effect on baby. A lot of data are available about effects of steroids, antibiotics, and mesalazine but no data are available about safety and efficacy of granulocyte-monocyte-apheresis (GMA) during pregnancy. In this case report, the 37 year-old pregnant woman with chronically active and steroid dependent ulcerative colitis (UC), at risk of abortion, refused more aggressive pharmacological therapeutic options and gave the informed consent to GMA. To minimize symptoms and the risk of severe clinical relapse, a maintenance GMA treatment was performed throughout pregnancy. The course of pregnancy was uneventful with no side effects; the mother and the baby were all healthy and well at the delivery.
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Affiliation(s)
- Valeria D'Ovidio
- GI Unit, Department of Internal Medicine and Medical Specialties, Policlinico Umberto I, University of Rome "La Sapienza", Sapienza, University of Rome, Italy
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22
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Ihara S, Yamaji Y, Kinoshita H, Yamada A, Hirata Y, Hasegawa K, Sugawara Y, Kokudo N, Koike K. First case report of de novo ulcerative colitis developing after orthotopic liver transplantation successfully treated by granulocyte and monocyte apheresis. Transplant Proc 2014; 46:2414-7. [PMID: 25015850 DOI: 10.1016/j.transproceed.2014.02.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2013] [Revised: 01/24/2014] [Accepted: 02/27/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Immunosuppressants such as tacrolimus and cyclosporine are prescribed long-term after orthotopic liver transplantation (OLT) to prevent allograft rejection. Although these immunosuppressants are known to effectively control ulcerative colitis (UC), some post-OLT patients develop exacerbation of preexisting UC or de novo UC. Although aminosalicylates and corticosteroid courses are usually effective to treat such UC, several patients have developed uncontrollable disease and required colectomies. CASE REPORT We have reported a patient who developed de novo UC after OLT to treat liver cirrhosis and hepatocellular carcinoma associated with hepatitis B virus (HBV) infection. Existence of the HBV infection made us avoid to increase the corticosteroid dose or to use other immunosuppressants such as azathioprine or infliximab. CONCLUSIONS In this patient, granulocyte and monocyte apheresis was highly effective in terms of inducing remission of de novo UC. No adverse event was noted.
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Affiliation(s)
- S Ihara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Yamaji
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
| | - H Kinoshita
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - A Yamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Hirata
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - K Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Y Sugawara
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - N Kokudo
- Hepato-Biliary-Pancreatic Surgery Division and Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - K Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
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Papi C, Fascì-Spurio F, Rogai F, Settesoldi A, Margagnoni G, Annese V. Mucosal healing in inflammatory bowel disease: treatment efficacy and predictive factors. Dig Liver Dis 2013; 45:978-985. [PMID: 24018244 DOI: 10.1016/j.dld.2013.07.006] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2013] [Revised: 05/21/2013] [Accepted: 07/13/2013] [Indexed: 02/06/2023]
Abstract
In recent years mucosal healing has emerged as an important therapeutic goal for patients with inflammatory bowel disease. Growing evidence suggests that achieving mucosal healing can improve patient outcomes and, potentially, alter the course of the disease. Drugs currently used in the management of inflammatory bowel disease are potentially able of inducing and maintaining mucosal healing, but the effect size is difficult to assess because of different definitions of mucosal healing, differences in study designs, and timing of endoscopic evaluation. Mucosal healing has been studied extensively in the biologic era. Data available from different sources, such as controlled trials and observational studies, show that anti-TNFα therapies can induce rapid and sustained mucosal healing in a variable percentage of patients with Crohn's disease and ulcerative colits. No controlled study has been designed to identify possible predictors of mucosal healing. Some clinical characteristics such as extensive disease, young age at diagnosis, and smoking status may be predictive of a more aggressive clinical course and, presumably, of a reduced clinical and endoscopic response to therapy. Changes and normalization of C-reactive protein and faecal calprotectin may be useful tools to predict outcomes, guide the timing for endoscopic evaluation and, possibly, reduce the need of endoscopic evaluation in assessing mucosal healing.
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Affiliation(s)
- Claudio Papi
- Gastroenterology & Hepatology Unit, San Filippo Neri Hospital, Rome, Italy.
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Vecchi M, Vernia P, Riegler G, D’Incà R, Annese V, Bagnoli S. Therapeutic landscape for ulcerative colitis: where is the Adacolumn(®) system and where should it be? Clin Exp Gastroenterol 2013; 6:1-7. [PMID: 23323022 PMCID: PMC3541711 DOI: 10.2147/ceg.s33275] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Granulocyte-monocyte apheresis is a relatively new therapy that has been proposed, sometimes with controversial results, for the treatment of inflammatory bowel disease, particularly ulcerative colitis. The aim of the present study was to perform a thorough review of the literature on the application of this type of treatment in ulcerative colitis and discuss the results, in order to provide an opinion on its use which is shared by the involved experts. The review of the literature was performed by searching PubMed with appropriate key words. The results obtained suggest that the major role for this treatment at this moment is for those patients with steroid dependency or with major contraindications to use of steroids. However, promising, albeit very preliminary, results have also been observed in steroid-naïve subjects, and this is of particular interest in consideration of the safety profile of this therapeutic method. As such, the Adacolumn may prove useful in specific subgroups of patients. Future phenotypic, genotypic, and molecular characterization of patients with inflammatory bowel disease might prove useful in defining better those subjects who might benefit most from this treatment modality.
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Affiliation(s)
- Maurizio Vecchi
- University of Milan, Department of Biomedical Sciences for Health, San Donato Milanese, Milan
| | - Piero Vernia
- Sapienza University of Rome, Department of Internal Medicine and Medical Specialties, Gastroenterology Unit, Rome
| | - Gabriele Riegler
- Second University of Naples, Gastroenterology and Endoscopy Unit, Naples
| | - Renata D’Incà
- University of Padua, Department of Surgical and Gastroenterological Science, Gastroenterology Unit, Padua
| | - Vito Annese
- University Hospital Careggi, Gastroenterology Unit, Florence, Italy
| | - Siro Bagnoli
- University Hospital Careggi, Gastroenterology Unit, Florence, Italy
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Shiraki M, Yamamoto T. Steroid-sparing strategies in the management of ulcerative colitis: Efficacy of leukocytapheresis. World J Gastroenterol 2012; 18:5833-8. [PMID: 23139598 PMCID: PMC3491589 DOI: 10.3748/wjg.v18.i41.5833] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2012] [Revised: 06/05/2012] [Accepted: 06/15/2012] [Indexed: 02/06/2023] Open
Abstract
Active ulcerative colitis (UC) is frequently associated with infiltration of a large number of leukocytes into the bowel mucosa. Leukocytapheresis is a novel nonpharmacologic approach for active UC, in which leukocytes are mechanically removed from the circulatory system. Current data indicate that leukocytapheresis is efficacious in improving response and remission rates with excellent tolerability and safety in patients with UC. Corticosteroid therapy remains a mainstay in the treatment of active UC; however, long-term, high doses of corticosteroids usually produce predictable and potentially serious side effects. If leukocytapheresis can spare patients from exposure to corticosteroids, the risk of steroid-induced adverse events should be minimized. This may be of great benefit to patients because severe side effects of steroids seriously impair health-related quality of life. In this article, we reviewed current evidence on whether leukocytapheresis can avoid or reduce the use of corticosteroids in the management of patients with UC. Several studies have shown that leukocytapheresis was effective for steroid-naïve patients with active UC. Furthermore, both short-term and long-term studies have demonstrated the steroid-sparing effects of leukocytapheresis therapy in patients with UC. Although the evidence level is not striking, the available data suggest that leukocytapheresis can avoid or reduce the use of corticosteroids in the management of UC. Large, well-designed clinical trials are necessary to more accurately evaluate the steroid-sparing effects of leukocytapheresis in the management of UC.
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C Leitner G, Worel N, Vogelsang H. Selective Granulocyte and Monocyte Apheresis as a Non-Pharmacological Option for Patients with Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2012; 39:246-252. [PMID: 22969694 DOI: 10.1159/000341801] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Accepted: 07/11/2012] [Indexed: 12/18/2022]
Abstract
Ulcerative colitis and Crohn's disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient's blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn( (®) ) (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba( (®) ) FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment.
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Affiliation(s)
- Gerda C Leitner
- University Clinic for Blood Group Serology and Transfusion Medicine, Vienna, Austria
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Cabriada JL, Domènech E, Ibargoyen N, Hernández V, Clofent J, Ginard D, Gutiérrez-Ibarluzea I, Hinojosa J. Leukocytapheresis for steroid-dependent ulcerative colitis in clinical practice: results of a nationwide Spanish registry. J Gastroenterol 2012; 47:359-65. [PMID: 22105230 DOI: 10.1007/s00535-011-0499-2] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 10/12/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND Several small, prospective, open studies suggest that leukocytapheresis might be efficient in patients with steroid-dependent ulcerative colitis (UC). AIM To evaluate the short- and long-term effectiveness of leukocytapheresis for the management of steroid-dependent UC in clinical practice. METHODS A Web-based, nationwide database specifically designed to record the efficacy and safety data of leukocytapheresis therapy in UC was available from September 2007 in Spain. Clinical data were collected at treatment baseline, 1 month after the last apheresis session (initial efficacy), and 6 and 12 months thereafter (long-term efficacy). Remission was defined as a Mayo Clinic index ≤2 together with complete steroid withdrawal and response as a decrease of ≥3 from the baseline score. RESULTS A total of 142 steroid-dependent UC patients were included in the registry, most of them treated with the Adacolumn™ system. In 69% of patients thiopurine therapy failed to achieve steroid-free clinical remission. Initial clinical remission was obtained in 37% of cases. The initial corticosteroid dose, the number and frequency of apheresis sessions, or the previous failure of thiopurines and/or infliximab did not influence the initial remission rate, but a greater decrease in CRP levels was associated with a higher probability to obtain initial remission. At 6 and 12 months, 41 and 36% of patients were in clinical remission, respectively. Only one serious adverse effect was recorded. CONCLUSIONS In clinical practice, apheresis allows long-term steroid-free clinical remission in up to one third of steroid-dependent UC patients, even in those with prior failure of thiopurines.
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Affiliation(s)
- J L Cabriada
- Hospital Galdakao-Usansolo, Galdakao, Vizcaya, Spain
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Cabriada JL. Aféresis en enfermedad inflamatoria intestinal. ¿Una opción válida? GASTROENTEROLOGIA Y HEPATOLOGIA 2012; 35:22-31. [DOI: 10.1016/j.gastrohep.2011.10.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2011] [Accepted: 10/19/2011] [Indexed: 12/16/2022]
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Daily granulocyte and monocyte adsorptive apheresis in patients with active ulcerative colitis: a prospective safety and feasibility study. J Gastroenterol 2011; 46:1003-9. [PMID: 21681409 DOI: 10.1007/s00535-011-0428-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2011] [Accepted: 05/08/2011] [Indexed: 02/04/2023]
Abstract
BACKGROUND This prospective study was to assess the safety and feasibility of daily granulocyte and monocyte adsorptive apheresis (GMA) therapy in patients with active ulcerative colitis (UC). METHODS Thirty consecutive patients with moderately or severely active UC received daily GMA treatment (5 sessions over 5 consecutive days) with the Adacolumn. Adverse events (AE), patient tolerability, and clinical symptoms were monitored daily. RESULTS Sixteen patients (53%) experienced AE during at least one GMA session. The most frequent AE was mild headache followed by fatigue and fever. None of the AE was serious, and all patients completed the 5 consecutive GMA sessions. Clinical symptoms (stool frequency and/or rectal bleeding) were improved in 21 patients (70%) during the course of GMA therapy. Clinical remission defined as normal stool frequency and no rectal bleeding was achieved in 7 patients (23%) after 5 GMA sessions. Seven of 20 patients (35%) with moderately active disease achieved clinical remission, whereas none of the 10 patients with severely active disease achieved clinical remission. Total and differential leukocyte counts, platelet count, and hemoglobin level did not significantly change, but C-reactive protein level significantly decreased during the course of GMA therapy. CONCLUSIONS This is the first report on daily GMA in the treatment of patients with UC. Daily GMA was safe and well tolerated without serious AE. Furthermore, daily GMA was associated with rapid improvement of clinical symptoms in patients with moderately active UC. However, controlled trials are warranted to assess a definite efficacy for daily GMA therapy.
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D'Ovidio V, Meo D, Viscido A, Bresci G, Vernia P, Caprilli R. Predictive factors of clinical response in steroid-refractory ulcerative colitis treated with granulocyte-monocyte apheresis. World J Gastroenterol 2011; 17:1831-5. [PMID: 21528055 PMCID: PMC3080717 DOI: 10.3748/wjg.v17.i14.1831] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2010] [Revised: 03/16/2010] [Accepted: 03/23/2010] [Indexed: 02/06/2023] Open
Abstract
AIM: To identify factors predicting the clinical response of ulcerative colitis patients to granulocyte-monocyte apheresis (GMA).
METHODS: Sixty-nine ulcerative colitis patients (39 F, 30 M) dependent upon/refractory to steroids were treated with GMA. Steroid dependency, clinical activity index (CAI), C reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), values at baseline, use of immunosuppressant, duration of disease, and age and extent of disease were considered for statistical analysis as predictive factors of clinical response. Univariate and multivariate logistic regression models were used.
RESULTS: In the univariate analysis, CAI (P = 0.039) and ESR (P = 0.017) levels at baseline were singled out as predictive of clinical remission. In the multivariate analysis steroid dependency [Odds ratio (OR) = 0.390, 95% Confidence interval (CI): 0.176-0.865, Wald 5.361, P = 0.0160] and low CAI levels at baseline (4 < CAI < 7) (OR = 0.770, 95% CI: 0.425-1.394, Wald 3.747, P = 0.028) proved to be effective as factors predicting clinical response.
CONCLUSION: GMA may be a valid therapeutic option for steroid-dependent ulcerative colitis patients with mild-moderate disease and its clinical efficacy seems to persist for 12 mo.
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Vernia P, D'Ovidio V, Meo D. Leukocytapheresis in the treatment of inflammatory bowel disease: Current position and perspectives. Transfus Apher Sci 2011; 43:227-9. [PMID: 20817610 DOI: 10.1016/j.transci.2010.07.023] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Therapeutic apheresis, a novel approach for immunodisorders, has been used in the last decade for the treatment of ulcerative colitis with promising result, and represents an alternative to conventional pharmacological therapy. Selective apheresis is aimed at reducing the number of circulating lymphocytes, interfering with recruitment and activation of mucosal granulocytes and macrophages, reducing cytokine and chemokine production which are thought to contribute to induction and perpetuation of inflammation. The article briefly reports indications, treatment schedule and clinical results of leukocytapheresis in ulcerative colitis. Available data for the two selective adsorption devices so far approved for clinical use (granulocyte-monocyte apheresis- Adacolumn- and leukocytapheresis-Cellsorba) are partially conflicting, and the number of controlled studies too small to draw definitive conclusions. Nonetheless apheresis definitely appears to be an effective non-conventional tool for the treatment of steroid refractory and steroid dependent UC patients with moderately active disease. The excellent safety profile of the procedure makes this approach attractive, both in adult and in pediatric patients, more so in those refractory to conventional drug therapy, who are presently treated with immunosuppressive and biological therapies.
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Affiliation(s)
- Piero Vernia
- GI Unit - Department of Clinical Sciences, Sapienza Università di Roma, V.le del Policlinico 155, 00161 Rome, Italy.
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Thanaraj S, Hamlin PJ, Ford AC. Systematic review: granulocyte/monocyte adsorptive apheresis for ulcerative colitis. Aliment Pharmacol Ther 2010; 32:1297-306. [PMID: 21050231 DOI: 10.1111/j.1365-2036.2010.04490.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with ulcerative colitis (UC) that is chronically active despite 5-aminosalicylates or immunomodulators, or who are dependent on corticosteroids to maintain remission, have limited treatment options. Granulocyte/monocyte adsorptive apheresis (GMAA) may have a role in this situation. AIM To conduct a systematic review of GMAA in UC. METHODS MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to identify randomized controlled trials (RCTs) comparing GMAA with conventional medical therapy, sham procedure or 'intensive' with 'conventional' GMAA regimens in adult UC patients. Studies reported clinical remission or response rates. RESULTS Ten RCTs were eligible. Formal meta-analysis was not undertaken due to concerns about methodological quality of identified studies. Compared with medical therapy, remission rates with GMAA were generally higher, and corticosteroid-sparing effects were observed. Compared with sham procedure, GMAA did not achieve significantly higher remission rates. 'Intensive' GMAA regimens demonstrated generally higher remission rates, and time to remission was shorter compared with 'conventional' regimens. Only two RCTs were at low risk of bias. Six were conducted in Japanese patients, which may limit generalizability. CONCLUSIONS Granulocyte/monocyte adsorptive apheresis appears of some benefit in UC. High-quality RCTs comparing granulocyte/monocyte adsorptive apheresis with conventional medical therapy or sham procedure in Western populations, with disease activity confirmed endoscopically, are required.
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Affiliation(s)
- S Thanaraj
- Leeds General Infirmary, Leeds Gastroenterology Institute, UK
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Lindberg A, Eberhardson M, Karlsson M, Karlén P. Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease. BMC Gastroenterol 2010; 10:73. [PMID: 20604939 PMCID: PMC2914086 DOI: 10.1186/1471-230x-10-73] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2010] [Accepted: 07/06/2010] [Indexed: 12/12/2022] Open
Abstract
Background Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity. Methods Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months. Results Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time. Conclusions IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.
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Affiliation(s)
- Annelie Lindberg
- Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset SE-118 83 Stockholm, Sweden
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Thanaraj S, Hamlin PJ, Ford AC. Is the benefit of granulocyte monocyte adsorptive apheresis in ulcerative colitis overstated? Dig Dis Sci 2010; 55:1803; author reply 1803-4. [PMID: 20431950 DOI: 10.1007/s10620-010-1188-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
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