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Tanaka T. Therapeutic Granulomonocytapheresis as a Non-pharmacologic Treatment Option for Inflammatory Bowel Disease: Efficacy Reports on a Wide Age Range and Disease Profile. Cureus 2023; 15:e48913. [PMID: 38106709 PMCID: PMC10725320 DOI: 10.7759/cureus.48913] [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: 11/16/2023] [Indexed: 12/19/2023] Open
Abstract
The major phenotypes of inflammatory bowel disease (IBD) include ulcerative colitis (UC) and Crohn's disease (CD), which cause debilitating symptoms, including bloody diarrhea, abdominal discomfort, and fever. Patients require life-long immunosuppressive medications, which cause adverse side effects as additional morbidity factors. However, IBD is initiated and perpetuated by inflammatory cytokines, and given that in patients with IBD myeloid lineage leukocytes are elevated with activation behavior and release inflammatory cytokines, selective depletion of elevated granulocytes and monocytes by granulomonocytapheresis is a relevant therapeutic option for IBD patients. Therefore, a column filled with specially designed beads as granulomonocytapheresis carriers for selective adsorption of myeloid lineage leukocytes (Adacolumn) has been applied to treat patients with active IBD. Patients receive up to 10 granulomonocytapheresis sessions at one or two sessions per week. During each session, the carriers adsorb up to 60% of the myeloid leukocytes from the blood that passes through the granulomonocytapheresis column. Efficacy rates in the UC setting have been as high as 85% in steroid-naïve patients, and 100% in drug-naïve, first-episode cases, but patients with a long duration of active IBD and extensive colonic lesions that have become refractory to pharmacological treatment have not responded well. However, granulomonocytapheresis has a favorable safety profile. Given that immunosuppressive medications used to treat IBD potentially may increase the risk of severe viral infection, non-drug granulomonocytapheresis should be a favorable treatment strategy. Further, by targeting granulomonocytapheresis to patients with background features and identifying a patient as a likely responder, futile use of medical resources is avoided.
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Affiliation(s)
- Tomotaka Tanaka
- Department of Gastroenterology, Tsuchiya General Hospital, Hiroshima, JPN
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de Carpi JM. Granulocyte and monocyte/macrophage apheresis in paediatric patients with ulcerative colitis: a case series in Spain. Drugs Context 2022; 11:2021-10-6. [PMID: 35371271 PMCID: PMC8932247 DOI: 10.7573/dic.2021-10-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 01/27/2022] [Indexed: 11/21/2022] Open
Abstract
Paediatric ulcerative colitis (UC) can cause malnutrition and growth retardation but its treatment can be limited by the potential adverse events of corticosteroids and anti-TNF agents in children. However, adsorptive granulocyte monocyte/macrophage apheresis (GMA) using Adacolumn® reduces intestinal inflammation through multiple immunomodulatory effects. This case series shows the safety and efficacy of GMA in paediatric UC, illustrating several GMA uses: in chronically active UC, for corticosteroid reduction in steroid-dependent UC, in UC with secondary loss of response to anti-TNF therapy, as bridge therapy in UC with failure of anti-TNF therapy, and to substitute toxic drug treatments.
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Affiliation(s)
- Javier Martin de Carpi
- Unit for Integral Care of Paediatric Inflammatory Bowel Disease, Gastroenterology, Hepatology and Nutrition Department, Hospital Sant Joan de Déu, Barcelona, Spain
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Chen XL, Mao JW, Wang YD. Selective granulocyte and monocyte apheresis in inflammatory bowel disease: Its past, present and future. World J Gastrointest Pathophysiol 2020; 11:43-56. [PMID: 32435521 PMCID: PMC7226913 DOI: 10.4291/wjgp.v11.i3.43] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 03/05/2020] [Accepted: 04/09/2020] [Indexed: 02/06/2023] Open
Abstract
The etiology and pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn’s disease, are not fully understood so far. Therefore, IBD still remains incurable despite the fact that significant progress has been achieved in recent years in its treatment with innovative medicine. About 20 years ago, selective granulocyte and monocyte apheresis (GMA) was invented in Japan and later approved by the Japanese health authority for IBD treatment. From then on this technique was extensively used for IBD patients in Japan and later in Europe. Clinical trials from Japan and European countries have verified the effectiveness and safety of GMA therapy in patients with IBD. In 2013, GMA therapy was approved by China State Food and Drug Administration for therapeutic use for the Chinese IBD patients. However, GMA therapy has not been extensively used in China, although a few clinical studies also showed that it was effective in clinical and endoscopic induction of remission in Chinese IBD patients with a high safety profile. This article reviews past history, present clinical application as well as the future prospective of GMA therapy for patients with IBD.
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Affiliation(s)
- Xiu-Li Chen
- Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Jing-Wei Mao
- Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
| | - Ying-De Wang
- Department of Gastroenterology, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China
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Motoya S, Tanaka H, Shibuya T, Osada T, Yamamoto T, Hongo H, Mizuno C, Saito D, Aoyama N, Kobayashi T, Ito H, Tanida S, Nojima M, Kokuma S, Hosoi E. Safety and effectiveness of granulocyte and monocyte adsorptive apheresis in patients with inflammatory bowel disease in special situations: a multicentre cohort study. BMC Gastroenterol 2019; 19:196. [PMID: 31752695 PMCID: PMC6873503 DOI: 10.1186/s12876-019-1110-1] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 11/07/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The available information on granulocyte and monocyte adsorptive apheresis (GMA) in patients with inflammatory bowel disease (IBD) under special situations remains unclear. We conducted a retrospective, multicentre cohort study to evaluate the safety and effectiveness of GMA in patients with IBD under special situations. METHODS This study included patients with ulcerative colitis (UC) or Crohn's disease who had at least one special situation feature and who had received GMA between November 2013 and March 2017. The incidence of adverse events (AEs) was compared in relation to the special situation, and patient background factors related to an AE were identified. For patients with UC, clinical remission was defined as a partial Mayo score of ≤2. RESULTS A total of 437 patients were included in this study. The incidence of AEs among the elderly patients (11.2%) was similar in all patients (11.4%), whereas the incidences of AEs in patients on multiple immunosuppressant medications (15.2%), patients with anaemia (18.1%) and paediatric/adolescent patients (18.9%) were higher than that in all patients (11.4%). In multivariate analysis, anaemia and concomitant immunosuppressant medications were independently associated with the incidence of AEs. Clinical remission was achieved in 46.4% of the patients with UC. CONCLUSIONS The incidence of AEs in the elderly patients was not higher than that in all patients, whereas the incidence of AE was higher in patients with anaemia and those on multiple immunosuppressant medications than that in all patients. GMA is a safe treatment option in elderly patients with IBD.
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Affiliation(s)
- Satoshi Motoya
- IBD Center, Sapporo Kosei General Hospital, Kita-3, Higashi-8, Chuo-ku, Sapporo, Hokkaido, 060-0033, Japan
| | - Hiroki Tanaka
- IBD Center, Sapporo Kosei General Hospital, Kita-3, Higashi-8, Chuo-ku, Sapporo, Hokkaido, 060-0033, Japan.
| | - Tomoyoshi Shibuya
- Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8431, Tokyo, Japan
| | - Taro Osada
- Department of Gastroenterology, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, 279-0021, Chiba, Japan
| | - Takayuki Yamamoto
- Department of Surgery & Inflammatory Bowel Disease Center, Yokkaichi Hazu Medical Center, 10-8 Hazuyamacho, Yokkaichi, 510-0016, Mie, Japan
| | - Hitoshi Hongo
- Fujita Gastroenterological Hospital, 17-36 Matsubaracho, Takatsuki, 569-0086, Osaka, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, 1-2 Kawazonocho, Suita, 564-0013, Osaka, Japan
| | - Daisuke Saito
- The Third Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, 181-8611, Tokyo, Japan
| | - Nobuo Aoyama
- Gastrointestinal Endoscopy and IBD Center, Aoyama Medical Clinic, 3-3-19 Tamondori, Chuo-ku, Kobe, 650-0015, Hyogo, Japan
| | - Toshihisa Kobayashi
- Department of Gastroenterology, Hakodate Goryoukaku Hospital, 38-3 Goryokakucho, Hakodate, 040-8611, Hokkaido, Japan
| | - Hiroaki Ito
- Kinshukai Infusion Clinic, 3-1 Ofukacho, Kita-ku, Osaka, 530-0011, Osaka, Japan
| | - Satoshi Tanida
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601, Aichi, Japan
| | - Masanori Nojima
- Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan
| | - Seiichiro Kokuma
- Medical affairs, JIMRO Co., Ltd, 351-1 Nishiyokote, Takasaki, 370-0021, Japan
| | - Eiji Hosoi
- Medical affairs, JIMRO Co., Ltd, 351-1 Nishiyokote, Takasaki, 370-0021, Japan
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Saniabadi AR, Tanaka T, Yamamoto T, Kruis W, Sacco R. Granulomonocytapheresis as a cell-dependent treatment option for patients with inflammatory bowel disease: Concepts and clinical features for better therapeutic outcomes. J Clin Apher 2018; 34:51-60. [PMID: 30407662 DOI: 10.1002/jca.21670] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Revised: 05/25/2018] [Accepted: 10/02/2018] [Indexed: 12/11/2022]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) are major phenotypes of the chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms. The chronic nature of IBD means that patients require life-long medications, and this may lead to drug dependency, loss of response together with adverse side effects as additional morbidity factors. The efficacy of antitumour necrosis factor (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation and perpetuation of IBD. However, cytokines are released by myeloid lineage leucocytes like the CD14+ CD16+ monocyte phenotype. Additionally in IBD, myeloid leucocytes are elevated with activation behavior, while lymphocytes are compromised. Therefore, patients' leucocytes appear logical targets of therapy. Adsorptive granulomonocytapheresis (GMA) with an Adacolumn uses carriers, which interact with the Fcγ receptor expressing leucocytes and deplete the elevated myeloid leucocytes, while the neutrophils, which re-enter the circulation via the Adacolumn outflow (≥40%) are phagocytosed by CD19 B-cells to become interleukin (IL)-10 producing Bregs or CD19high CD1Dhigh B-cells. IL-10 is an anti-inflammatory cytokine. GMA has been applied to treat patients with IBD. The efficacy outcomes have been impressive as well as disappointing, the clinical response to GMA defines the patients' disease course and severity at entry. Efficacy outcomes in patients with deep ulcers together with extensive loss of the mucosal tissue are not encouraging, while patients without these features respond well and attain a favorable long-term disease course. Accordingly, for responder patients, GMA fulfills a desire to be treated without drugs.
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Affiliation(s)
| | - Tomotaka Tanaka
- Department of Gastroenterology, Akitsu Prefectural Hospital, Hiroshima, Japan
| | - Takayuki Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Yokkaichi, Japan
| | - Wolfgang Kruis
- Evangelisches Krankenhaus Kalk, Cologen University, Cologne, Germany
| | - Rodolfo Sacco
- Department of Gastroenterology, Pisa University Hospital, Pisa, Italy
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Fujita H, Terui T, Hayama K, Akiyama M, Ikeda S, Mabuchi T, Ozawa A, Kanekura T, Kurosawa M, Komine M, Nakajima K, Sano S, Nemoto O, Muto M, Imai Y, Yamanishi K, Aoyama Y, Iwatsuki K. Japanese guidelines for the management and treatment of generalized pustular psoriasis: The new pathogenesis and treatment of GPP. J Dermatol 2018; 45:1235-1270. [PMID: 30230572 DOI: 10.1111/1346-8138.14523] [Citation(s) in RCA: 166] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 05/25/2018] [Indexed: 05/01/2024]
Abstract
Generalized pustular psoriasis (GPP) is a rare disease characterized by recurrent fever and systemic flushing accompanied by extensive sterile pustules. The committee of the guidelines was founded as a collaborative project between the Japanese Dermatological Association and the Study Group for Rare Intractable Skin Diseases under the Ministry of Health, Labour, and Welfare Research Project on Overcoming Intractable Diseases. The aim of the guidelines was to provide current information to aid in the treatment of patients with GPP in Japan. Its contents include the diagnostic and severity classification criteria for GPP, its pathogenesis, and recommendations for the treatment of GPP. Since there are few clinical trial data with high levels of evidence for this rare disease, recommendations by the committee are described in the present guidelines.
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Affiliation(s)
- Hideki Fujita
- Division of Dermatological Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Tadashi Terui
- Division of Dermatological Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Koremasa Hayama
- Division of Dermatological Science, Department of Dermatology, Nihon University School of Medicine, Tokyo, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shigaku Ikeda
- Department of Dermatology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Tomotaka Mabuchi
- Department of Dermatology, Tokai University School of Medicine, Isehara, Japan
| | - Akira Ozawa
- Department of Dermatology, Tokai University School of Medicine, Isehara, Japan
| | - Takuro Kanekura
- Department of Dermatology, Kagoshima University School of Medicine, Kagoshima, Japan
| | - Michiko Kurosawa
- Department of Epidemiology and Environmental Health, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Mayumi Komine
- Department of Dermatology, Jichi Medical University, Shimotsuke, Japan
| | - Kimiko Nakajima
- Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan
| | - Shigetoshi Sano
- Department of Dermatology, Kochi Medical School, Kochi University, Nankoku, Japan
| | | | - Masahiko Muto
- Department of Dermatology, Yamaguchi University School of Medicine, Ube, Japan
| | - Yasutomo Imai
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Kiyofumi Yamanishi
- Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Yumi Aoyama
- Department of Dermatology, Kawasaki Medical School, Kurashiki, Japan
| | - Keiji Iwatsuki
- Department of Dermatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan
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7
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Turner D, Ruemmele FM, Orlanski-Meyer E, Griffiths AM, de Carpi JM, Bronsky J, Veres G, Aloi M, Strisciuglio C, Braegger CP, Assa A, Romano C, Hussey S, Stanton M, Pakarinen M, de Ridder L, Katsanos K, Croft N, Navas-López V, Wilson DC, Lawrence S, Russell RK. Management of Paediatric Ulcerative Colitis, Part 1: Ambulatory Care-An Evidence-based Guideline From European Crohn's and Colitis Organization and European Society of Paediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr 2018; 67:257-291. [PMID: 30044357 DOI: 10.1097/mpg.0000000000002035] [Citation(s) in RCA: 305] [Impact Index Per Article: 43.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of pediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). An extensive literature search with subsequent evidence appraisal using robust methodology was performed before 2 face-to-face meetings. All 40 included recommendations and 86 practice points were endorsed by 43 experts in Paediatric IBD with at least an 88% consensus rate. RESULTS These guidelines discuss how to optimize the use of mesalamine (including topical), systemic and locally active steroids, thiopurines and, for more severe disease, biologics. The use of other emerging therapies and the role of surgery are also covered. Algorithms are provided to aid therapeutic decision-making based on clinical assessment and the Paediatric UC Activity Index (PUCAI). Advice on contemporary therapeutic targets incorporating the use of calprotectin and the role of therapeutic drug monitoring are presented, as well as other management considerations around pouchitis, extraintestinal manifestations, nutrition, growth, psychology, and transition. A brief section on disease classification using the PIBD-classes criteria and IBD-unclassified is also part of these guidelines. CONCLUSIONS These guidelines provide a guide to clinicians managing children with UC and IBD-unclassified management to provide modern management strategies while maintaining vigilance around appropriate outcomes and safety issues.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Frank M Ruemmele
- Université Paris Descartes, Sorbonne Paris Cité, APHP, Hôpital Necker Enfants Malades, Paris, France
| | | | - Anne M Griffiths
- The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | | | - Jiri Bronsky
- Department of Paediatrics, University Hospital Motol, Prague, Czech Republic
| | - Gabor Veres
- 1st Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Marina Aloi
- Pediatric Gastroenterology and Liver Unit, Sapienza University of Rome, Rome, Italy
| | - Caterina Strisciuglio
- Department of Woman, Child and General and Specialistic Surgery, University of Campania "Luigi Vanvitelli," Napoli, Italy
| | | | - Amit Assa
- Schneider Children's Hospital, Petach Tikva, Affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Claudio Romano
- Pediatric Department, University of Messina, Messina, Italy
| | - Séamus Hussey
- National Children's Research Centre, Royal College of Surgeons of Ireland and University College Dublin, Dublin, Ireland
| | | | - Mikko Pakarinen
- Helsinki University Children's Hospital, Department of Pediatric Surgery, Helsinki, Finland
| | - Lissy de Ridder
- Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | | | - Nick Croft
- Barts and the London School of Medicine, Queen Mary University of London, London, UK
| | - Victor Navas-López
- Pediatric Gastroenterology and Nutrition Unit. Hospital Materno, IBIMA, Málaga, Spain
| | - David C Wilson
- Child Life and Health, University of Edinburgh, Edinburgh, UK
| | - Sally Lawrence
- BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada
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8
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Tanaka T, Yamamoto T, Sawada K, Sacco R. Treatment options for children and adolescents with inflammatory bowel disease: is granulomonocytapheresis an effective alternative to drug therapy? Expert Rev Gastroenterol Hepatol 2017; 11:749-758. [PMID: 28612637 DOI: 10.1080/17474124.2017.1341309] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Patients with inflammatory bowel diseases (IBD) require life-long medications, which even if effective have the potential to cause adverse effects as additional morbidity factors. In pediatric patients, drug therapy has more serious limitations, including impaired physical and mental development. A non-drug therapeutic option is believed to be depletion of elevated and activated granulocytes and monocytes known to release inflammatory cytokines, like the CD14+CD16+ monocyte phenotype known to release tumor necrosis factor-α. Areas covered: Granulomonocyteapheresis (GMA) with an Adacolumn as a treatment option for IBD patients has been applied for the past 15 years. This article reviews the argument that GMA is a relevant and effective non-pharmacologic intervention in pediatric IBD setting. Expert commentary: GMA with an Adacolumn has shown promise in adult, pediatric, and adolescent patients with active IBD. There is evidence of post-GMA immunomodulation in terms of increased regulatory T-cell and B-cell activities. Additionally, patients who respond to GMA may attain a favorable long-term clinical course by avoiding pharmacologicals during an early phase of their active IBD. GMA has a good safety profile, especially in difficult-to-treat and pediatric settings. An additional trial is warranted to assess the efficacy of GMA in the early phase of pediatric IBD to optimize patient selection.
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Affiliation(s)
- Tomotaka Tanaka
- a Department of Gastroenterology , Akitsu Prefectural Hospital , Hiroshima , Japan
| | - Takayuki Yamamoto
- b Inflammatory Bowel Disease Centre , Yokkaichi Hazu Medical Centre , Mie , Japan
| | - Koji Sawada
- c Department of Gastroenterology , Chionkai Dojima General & Gastroenterology Clinic , Osaka , Japan
| | - Rodolfo Sacco
- d Department of Gastroenterology , Cisanello Pisa University Hospital, Gastroenterology and Metabolic Diseases Unit , Pisa , Italy
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9
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Saniabadi AR, Tanaka T, Ohmori T, Sawada K, Yamamoto T, Hanai H. Treating inflammatory bowel disease by adsorptive leucocytapheresis: A desire to treat without drugs. World J Gastroenterol 2014; 20:9699-9715. [PMID: 25110409 PMCID: PMC4123360 DOI: 10.3748/wjg.v20.i29.9699] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2013] [Revised: 01/20/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Ulcerative colitis and Crohn’s disease are the major phenotypes of the idiopathic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms, impairing function and quality of life. Current medications are aimed at reducing the symptoms or suppressing exacerbations. However, patients require life-long medications, and this can lead to drug dependency, loss of response together with adverse side effects. Indeed, drug side effects become additional morbidity factor in many patients on long-term medications. Nonetheless, the efficacy of anti-tumour necrosis factors (TNF)-α biologics has validated the role of inflammatory cytokines notably TNF-α in the exacerbation of IBD. However, inflammatory cytokines are released by patients’ own cellular elements including myeloid lineage leucocytes, which in patients with IBD are elevated with activation behaviour and prolonged survival. Accordingly, these leucocytes appear logical targets of therapy and can be depleted by adsorptive granulocyte/monocyte apheresis (GMA) with an Adacolumn. Based on this background, recently GMA has been applied to treat patients with IBD in Japan and in the European Union countries. Efficacy rates have been impressive as well as disappointing. In fact the clinical response to GMA seems to define the patients’ disease course, response to medications, duration of active disease, and severity at entry. The best responders have been first episode cases (up to 100%) followed by steroid naïve and patients with a short duration of active disease prior to GMA. Patients with deep ulcers together with extensive loss of the mucosal tissue and cases with a long duration of IBD refractory to existing medications are not likely to benefit from GMA. It is clinically interesting that patients who respond to GMA have a good long-term disease course by avoiding drugs including corticosteroids in the early stage of their IBD. Additionally, GMA is very much favoured by patients for its good safety profile. GMA in 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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10
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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
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11
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Turner D, Levine A, Escher JC, Griffiths AM, Russell RK, Dignass A, Dias JA, Bronsky J, Braegger CP, Cucchiara S, de Ridder L, Fagerberg UL, Hussey S, Hugot JP, Kolacek S, Kolho KL, Lionetti P, Paerregaard A, Potapov A, Rintala R, Serban DE, Staiano A, Sweeny B, Veerman G, Veres G, Wilson DC, Ruemmele FM. Management of pediatric ulcerative colitis: joint ECCO and ESPGHAN evidence-based consensus guidelines. J Pediatr Gastroenterol Nutr 2012; 55:340-61. [PMID: 22773060 DOI: 10.1097/mpg.0b013e3182662233] [Citation(s) in RCA: 274] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Pediatric ulcerative colitis (UC) shares many features with adult-onset disease but there are some unique considerations; therefore, therapeutic approaches have to be adapted to these particular needs. We aimed to formulate guidelines for managing UC in children based on a systematic review (SR) of the literature and a robust consensus process. The present article is a product of a joint effort of the European Crohn's and Colitis Organization (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). METHODS A group of 27 experts in pediatric IBD participated in an iterative consensus process including 2 face-to-face meetings, following an open call to ESPGHAN and ECCO members. A list of 23 predefined questions were addressed by working subgroups based on a SR of the literature. RESULTS A total of 40 formal recommendations and 68 practice points were endorsed with a consensus rate of at least 89% regarding initial evaluation, how to monitor disease activity, the role of endoscopic evaluation, medical and surgical therapy, timing and choice of each medication, the role of combined therapy, and when to stop medications. A management flowchart, based on the Pediatric Ulcerative Colitis Activity Index (PUCAI), is presented. CONCLUSIONS These guidelines provide clinically useful points to guide the management of UC in children. Taken together, the recommendations offer a standardized protocol that allows effective, timely management and monitoring of the disease course, while acknowledging that each patient is unique.
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Affiliation(s)
- Dan Turner
- Shaare Zedek Medical Center, The Hebrew University of Jerusalem, Israel.
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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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Abstract
OBJECTIVE Leukocytapheresis (LCAP) is a nonpharmacologic therapy that has recently been used to treat ulcerative colitis (UC). This multicenter open-label study prospectively assessed the efficacy and safety of LCAP in pediatric patients with UC. PATIENTS AND METHODS Twenty-three patients ages 8 to 16 years with moderate (n = 19) to severe (n = 4) steroid-resistant UC were enrolled. One of 2 LCAP columns with different volumes (model EX and the half-volume model EI) was selected, according to body weight. LCAP was performed once per week for 5 consecutive weeks. Clinical and laboratory data were collected at predetermined time points. The primary endpoint was decreased stool frequency/hematochezia score, and secondary endpoints were clinical, laboratory, and endoscopic improvements. RESULTS The stool frequency/hematochezia score decreased significantly from 4.5 ± 1.2 before treatment to 1.6 ± 1.9 after the fifth treatment. Clinical parameters, including stool frequency, presence of visible blood, abdominal pain, and body temperature, were significantly improved. Fecal calprotectin decreased significantly. Endoscopic findings evaluated using Matts score also improved (P < 0.01). The steroid dose decreased from 1.1 ± 0.4 mg/kg before treatment to 0.8 ± 0.5 mg/kg after treatment. There were no significant differences in changes between the EX and EI columns. The incidence of adverse effects was 61%, although none was serious. The most common adverse effects were decreased hematocrit and hemoglobin concentration. CONCLUSIONS The present study showed that LCAP was well tolerated in children with UC, mostly moderate, and was as effective as in adults. The types of pediatric patients best suited to LCAP remain to be determined.
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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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Abstract
Ulcerative colitis is a chronic inflammatory disease that affects the colon and rectum. Its pathogenesis is probably multifactorial including the influx of certain cytokines into the colonic mucosa, causing disease activity and relapse. The hypothesis of removing such cytokines from the circulation by leukocytapheresis was implemented to reduce disease activity, maintain remission, and prevent relapse. Many recent reports not only in Japan, but also in the West, have highlighted its beneficial effects in both adult and pediatric patients. Large placebo-controlled studies are needed to confirm the available data in this regard. In this article, we shed some light on the use of leukocyte apheresis in the management of autoimmune diseases, especially ulcerative colitis.
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Affiliation(s)
- Ahmed Helmy
- Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
| | - Maheeba Abdulla
- Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Ingvar Kagevi
- Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
| | - Khalid Al Kahtani
- Section of Gastroenterology, Department of Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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Nos P, Domènech E. Tratamiento con aféresis en la enfermedad inflamatoria intestinal. GASTROENTEROLOGIA Y HEPATOLOGIA 2009; 32:509-18. [DOI: 10.1016/j.gastrohep.2009.01.183] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/25/2008] [Accepted: 01/13/2009] [Indexed: 02/07/2023]
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Ruuska T, Wewer V, Lindgren F, Malmborg P, Lindquist M, Marthinsen L, Browaldh L, Casswall T, Kalliomäki M, Grönlund J. Granulocyte-monocyte adsorptive apheresis in pediatric inflammatory bowel disease: results, practical issues, safety, and future perspectives. Inflamm Bowel Dis 2009; 15:1049-54. [PMID: 19137602 DOI: 10.1002/ibd.20859] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND The purpose of the study was to collect data on granulocyte-monocyte adsorptive apheresis (GMA) for the treatment of corticosteroid-dependent (SD) or corticosteroid-resistant (SR) inflammatory bowel disease (IBD) in children from 3 Nordic countries to evaluate its efficacy and safety and to assess practical issues. METHODS Retrospective data on 37 children treated with GMA were collected. In all, 22 children had ulcerative colitis (UC), 13 Crohn's disease (CD), and 2 had indeterminate colitis (IC). Their mean age was 13.2 years, range 5-17 years, and mean duration of disease was 2.4 years, range 1 month to 6 years. Indication for treatment in the UC group was SD in 11 cases, SR in 6 cases, and other reasons in 5 cases. The corresponding numbers in the CD group were SD in 8 cases, SR in 2 cases, and other reasons in 3 cases. In the IC group, 1 had SD and 1 was refractory to steroids, azathioprine, and infliximab. Efficacy was evaluated by severity indices: the Pediatric Ulcerative Colitis Activity Index (PUCAI) and the Pediatric Crohn's Disease Activity Index (PCDAI) and tapering of corticosteroids. RESULTS PUCAI and PCDAI decreased significantly in both groups after 3 months (P = 0.0007, P = 0.025). The dosage of corticosteroid was significantly reduced in the UC group by the end of GMA (P = 0.004) and this response continued after 3 months. Relapse was seen in 2 patients with UC and 3 patients with CD after 3 months follow-up. CONCLUSIONS GMA seems to be an effective and safe treatment in 81% of the SD or SR pediatric IBD patients, especially in those with UC.
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Affiliation(s)
- T Ruuska
- Department of Paediatrics, Tampere University Hospital, Finland.
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Dittrich K, Richter M, Rascher W, Köhler H. Leukocytapheresis in a girl with severe ulcerative colitis refractory to corticosteroids, infliximab, and cyclosporine A. Inflamm Bowel Dis 2008; 14:1466-7. [PMID: 18421764 DOI: 10.1002/ibd.20464] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
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Leukocytapheresis for the treatment of IBD. ACTA ACUST UNITED AC 2008; 5:509-16. [PMID: 18665138 DOI: 10.1038/ncpgasthep1209] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2008] [Accepted: 06/24/2008] [Indexed: 02/06/2023]
Abstract
Leukocytapheresis is a controversial nonpharmacologic treatment for IBD, in which white blood cells--the effector cells of the inflammatory process--are mechanically removed from the circulation. Current controversy centers on the uncontrolled nature of the leukocytapheresis trials performed and their use of different outcome measures in patient groups that have very variable disease activity and severity. Nonetheless, the efficacy data obtained are generally quite consistent: an excellent response (remission >80%) has been achieved in corticosteroid-naïve patients with ulcerative colitis and an average remission rate of more than 50% has been achieved in patients who have steroid-dependent or refractory ulcerative colitis. Interestingly, the largest randomized, double-blind, sham-controlled study of granulocyte-monocyte apheresis in patients with moderate to severe ulcerative colitis failed to demonstrate efficacy for the induction of clinical remission or response. Regardless, leukocytapheresis seems to be remarkably safe. The precise positioning of leukocytapheresis in the treatment of ulcerative colitis is uncertain at present and will vary according to geography and patient preference for a safe, nonpharmacologic treatment. Further efficacy studies are required to assess what the optimal number and frequency of treatments is, in addition to the need for head-to-head comparisons with established drugs.
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Safety and efficacy of granulocyte and monocyte adsorption apheresis in paediatric inflammatory bowel disease: a prospective pilot study. J Pediatr Gastroenterol Nutr 2008; 46:386-91. [PMID: 18367949 DOI: 10.1097/mpg.0b013e31815604e5] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Selective granulocyte-monocyte adsorption (GMA) apheresis is a safe technique that has shown efficacy in inflammatory bowel disease (IBD), especially in adult steroid-dependent and steroid-refractory ulcerative colitis. GMA apheresis is performed with Adacolumn, a direct blood perfusion system that selectively adsorbs circulating granulocytes and monocytes. Studies on efficacy of GMA apheresis in paediatric IBD are scarce. Our aim was to evaluate efficacy, safety, and tolerability of GMA apheresis in paediatric IBD patients followed for 1 year. PATIENTS AND METHODS Nine patients with a mild to moderate flare-up (6 boys, 3 girls; 5 ulcerative colitis [UC], 4 Crohn disease [CD]) were included. Mean age at inclusion was 13 years and 9 months, and mean disease duration before inclusion was 28 months. All of our patients with UC were steroid-dependent; patients with CD had been unsuccessfully treated with other therapies. GMA apheresis consisted of 5 consecutive weekly sessions lasting 60 minutes each. RESULTS After the 5 sessions, 4 of 5 patients with UC and 1 of 4 patients with CD achieved remission. This remission was maintained in 2 of 4 patients with UC and in the single patients with CD. Patients taking steroids could begin to taper their daily doses after the second apheresis, and 3 of 5 of these patients reached the end of the study steroid-free. GMA apheresis was well tolerated and no severe side effects related to the technique were observed. CONCLUSIONS GMA apheresis is a safe, well-tolerated technique in paediatric IBD. As previously reported, we have observed a better efficacy in promoting and maintaining remission, and reducing conventional drugs in patients with UC than in patients with CD.
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Noguchi A, Watanabe K, Narumi S, Yamagami H, Fujiwara Y, Higuchi K, Oshitani N, Arakawa T. The production of interferon-gamma-inducible protein 10 by granulocytes and monocytes is associated with ulcerative colitis disease activity. J Gastroenterol 2007; 42:947-56. [PMID: 18085351 DOI: 10.1007/s00535-007-2118-9] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2006] [Accepted: 09/18/2007] [Indexed: 02/04/2023]
Abstract
BACKGROUND To clarify which types of cells produce interferon-gamma-inducible protein 10 (IP-10) and whether IP-10 is associated with the development of ulcerative colitis (UC), we investigated IP-10 production in UC patients. METHODS Serum IP-10 levels were measured using enzyme-linked immunosorbent assay in 29 patients with active and 21 with inactive UC and in 20 controls. The production of IP-10 by granulocytes and monocytes adsorbed to G-1 beads was examined. In 21 active UC patients treated with granulocyte and monocyte/macrophage adsorptive apheresis (GMA), serum IP-10 levels were measured before and after treatment. IP-10-positive cells in UC mucosa were also examined immunohistochemically using tissues obtained by surgical resection and colonoscopic biopsies. RESULTS Serum IP-10 levels in active UC patients were significantly higher than those in inactive patients, although even in the latter the levels were increased compared with those in controls. IP-10 production by granulocytes and monocytes in active UC patients was significantly higher than that in controls. Furthermore, the number of IP-10-positive cells was elevated in the colonic mucosa of patients with active UC, and one of the main subpopulations of IP-10-positive cells was granulocytes. Serum IP-10 levels decreased following GMA treatment in responders, but not in nonresponders. Interestingly, serum IP-10 levels before GMA were higher in responders than in nonresponders. In parallel with the serum levels, IP-10-positive cells also decreased following GMA treatment. CONCLUSIONS Serum IP-10 levels reflected UC disease activity, and the source of IP-10 was granulocytes and monocytes. Furthermore, serum IP-10 levels may be a marker for the responsiveness of patients to GMA treatment.
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Affiliation(s)
- Atsushi Noguchi
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan
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22
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Abstract
The etiology of inflammatory bowel disease (IBD) is not completely understood, thus current therapies have been empirical and directed at treating symptoms rather than addressing the cause. In IBD, the overexpression of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, leads to a persistent intestinal inflammatory response that damages the intestinal mucosa. Recent advances in pharmacologic therapies that target specific cytokines, chemokines, and adhesion molecules have proved successful in alleviating symptoms for some patients. There are 2 selective adsorption apheresis devices that remove leukocytes from whole blood, which are currently available in Japan and Europe-the Cellsorba leukocytapheresis column and the Adacolumn adsorptive extracorporeal granulocyte/monocyte apheresis device. The purported mechanisms of action of these devices have been extensively reviewed and are believed to exert an immunomodulatory and/or anti-inflammatory effect on patients with systemic inflammatory disease. The clinical trials presented here indicate that selective leukocyte apheresis effectively removes activated granulocytes and monocytes/macrophages from peripheral blood while maintaining an excellent safety profile. Despite these findings, large controlled trials of selective leukocyte apheresis in the treatment of IBD are needed to determine the true efficacy of this approach.
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Kumagai M, Yamato Y, Maeda K, Nakashima E, Ushijima K, Kimura A. Extracorporeal leukocyte removal therapy for patients with ulcerative colitis. Pediatr Int 2007; 49:431-6. [PMID: 17587263 DOI: 10.1111/j.1442-200x.2007.02392.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND The purpose of the present paper was to investigate efficacy of leukocytapheresis (LCAP) or granulocytapheresis (GCAP) in pediatric patients with ulcerative colitis (UC), including reduction of the total dose and side-effects of corticosteroids. METHODS Courses of five Japanese adolescents with UC were analyzed. Four patients had recurrent UC with repeated remissions and exacerbations despite therapy including 5-aminosalicylic acid in combination with a corticosteroid. The other patient had a first attack. Effectiveness of adding LCAP or GCAP was assessed with regard to short-term changes in clinical activity, complications, and longer-term outcome. RESULTS Clinical improvement was attained in three patients, while the other two did not improve and underwent colectomy. One of the two patients had moderately severe complications from LCAP and showed increased clinical activity during LCAP. The other, who began therapy with LCAP alone, had moderate improvement only after addition of a corticosteroid. CONCLUSION Additional studies are needed to determine optimum timing of LCAP or GCAP and initiation of remission-maintenance therapy.
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Affiliation(s)
- Masami Kumagai
- Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan
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Yamamoto T, Saniabadi AR, Maruyama Y, Umegae S, Matsumoto K. Factors affecting clinical and endoscopic efficacies of selective leucocytapheresis for ulcerative colitis. Dig Liver Dis 2007; 39:626-33. [PMID: 17532273 DOI: 10.1016/j.dld.2007.04.007] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2006] [Revised: 02/18/2007] [Accepted: 04/18/2007] [Indexed: 12/11/2022]
Abstract
BACKGROUND Granulocyte, monocyte/macrophage adsorptive apheresis is a novel treatment for active ulcerative colitis. However, as yet no study has reported on a subset of patients who might respond well to granulocyte, monocyte/macrophage adsorptive apheresis therapy. AIM To identify factors affecting clinical and endoscopic efficacies of granulocyte, monocyte/macrophage in patients with ulcerative colitis. METHODS Fifty consecutive patients with active ulcerative colitis initially received five granulocyte, monocyte/macrophage adsorptive apheresis sessions with the Adacolumn over five consecutive weeks. Patients who improved without achieving remission received five additional granulocyte, monocyte/macrophage adsorptive apheresis sessions. RESULTS One week after the last granulocyte, monocyte/macrophage adsorptive apheresis session, 26 (52%) and 17 patients (34%) achieved clinical and endoscopic remission, respectively. In the multivariate analysis, the dose of prednisolone administered at entry and the cumulative dose of prednisolone administered before entry were independent significant factors for both clinical and endoscopic remission, negatively impacted the efficacy of granulocyte, monocyte/macrophage adsorptive apheresis. Age, gender, duration of ulcerative colitis, number of prior relapses, duration of current exacerbation, extent and severity of ulcerative colitis, extra-intestinal manifestations, entry haematology values and C-reactive protein did not affect the outcome. CONCLUSIONS Based on the outcomes of this study, it appears that steroid-naïve patients and patients on low dose steroid and short duration of exposure respond to granulocyte, monocyte/macrophage adsorptive apheresis. Further studies in larger cohorts of patients should strengthen our findings.
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Affiliation(s)
- T Yamamoto
- Inflammatory Bowel Disease Centre, Yokkaichi Social Insurance Hospital, 10-8 Hazuyamacho, Yokkaichi, Mie 510-0016, Japan.
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Caprilli R, D'Ovidio V. Leukocytapheresis as promising therapy for inflammatory bowel disease. Dig Liver Dis 2007; 39:435-7. [PMID: 17379590 DOI: 10.1016/j.dld.2007.02.003] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2007] [Accepted: 02/09/2007] [Indexed: 12/11/2022]
Affiliation(s)
- R Caprilli
- Department of Clinical Sciences, GI Unit, Policlinico Umberto I, University of Rome, La Sapienza, Rome, Italy.
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Suzuki Y, Yoshimura N, Fukuda K, Shirai K, Saito Y, Saniabadi AR. A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci 2006; 51:2031-8. [PMID: 17004123 DOI: 10.1007/s10620-006-9199-9] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2005] [Accepted: 12/05/2005] [Indexed: 12/12/2022]
Abstract
Recently, selective granulocytapheresis (Adacolumn) has appeared as a new treatment for patients with inflammatory bowel disease. This study sought to determine predictors of response to this new nonpharmacologic mode of therapy by retrospectively evaluating 28 patients who received granulocytapheresis after experiencing active ulcerative colitis (UC). Between April 2000 and March 2004, 28 consecutive patients received granulocytapheresis for active UC with the Adacolumn, which is filled with cellulose acetate beads as the column leukocytapheresis carriers; the carriers adsorb granulocytes, monocytes/macrophages, and a small fraction of lymphocytes (FcgammaR and complement receptors bearing leukocytes). Each patient could receive up to 10 Adacolumn sessions, at 2 sessions per week. In 2004, clinical response was retrospectively evaluated. Seven days after the last Adacolumn session, 20 of 28 patients had remission (colitis activity index [CAI] < or =4) including all 8 patients who had their first UC episode. The mean duration of UC in the 8 first episode cases was 3.4 months compared with 40.2 months for all 28 patients and 65.4 months for the 8 nonresponders. The response to Adacolumn was independent of basal CAI. The 8 nonresponders were given conventional medication (CM) or cyclosporine (CsA) if the former failed. Two responded to CM, 3 to CsA, and 3 underwent colectomy. First UC episode and short disease duration appear good predictors of response to granulocytapheresis. Selective granulocytapheresis might be an effective first-line treatment.
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Affiliation(s)
- Yasuo Suzuki
- Department of Internal Medicine, Sakura Hospital, Toho University, Chiba University School of Medicine, Tokyo, Japan.
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Ikeda H, Ishimaru Y, Takayasu H, Fujino J, Kisaki Y, Otani Y, Yamagishi J, Tahara K. Efficacy of granulocyte apheresis in pediatric patients with ulcerative colitis: a pilot study. J Pediatr Gastroenterol Nutr 2006; 43:592-6. [PMID: 17130733 DOI: 10.1097/01.mpg.0000237928.07729.79] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
OBJECTIVES Granulocyte apheresis (GCAP), involving the removal of granulocytes from the blood, may improve clinical symptoms and facilitate a reduction in the dose of steroids in adult patients with ulcerative colitis. As a preliminary trial, GCAP was used to taper the dose of steroids in 4 pediatric patients with ulcerative colitis. METHODS Three males and 1 female ranging from 11 to 17 years old were treated with GCAP once per week for 5 consecutive weeks/course. The ages of patients at clinical onset ranged from 8 to 12 years and the length of time from the clinical onset to GCAP treatment ranged from 28 to 58 months (median, 38.5 months). RESULTS In 2 patients, symptoms and signs indicating disease activity improved after 2 courses of GCAP. Laboratory data and endoscopic findings also improved after treatment and the clinical efficacy was judged to be excellent in these patients. In 1 patient, GCAP improved laboratory and endoscopic hallmarks, but bloody stools persisted. Finally, the treatment was ineffective in the fourth patient who eventually underwent surgery. CONCLUSIONS GCAP is effective in improving clinical symptoms and may play an important role in converting steroid therapy to other treatments in children with steroid-refractory or steroid-dependent ulcerative colitis.
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Affiliation(s)
- Hitoshi Ikeda
- Department of Pediatric Surgery, Dokkyo University School of Medicine, Koshigaya Hospital, Koshigaya, Japan.
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Abstract
Ulcerative colitis is an important disease in the paediatric population. Ulcerative colitis is one of the chronic inflammatory bowel diseases, and is medically incurable. However, the arsenal of medications has grown as knowledge of the pathogenesis of this disease advances. This review looks at the classical treatments for children with ulcerative colitis, including the 5-aminosalicylates, corticosteroids and imunomodulators, as well as biological therapy and other, newer modalities.
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Affiliation(s)
- Melanie K Greifer
- Division of Pediatric Gastroenterology and Nutrition, Schneider Children's Hospital, 269-01 76th Avenue, New Hyde Park, New York 11040, USA
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D'Ovidio V, Aratari A, Viscido A, Marcheggiano A, Papi C, Capurso L, Caprilli R. Mucosal features and granulocyte-monocyte-apheresis in steroid-dependent/refractory ulcerative colitis. Dig Liver Dis 2006; 38:389-94. [PMID: 16569521 DOI: 10.1016/j.dld.2005.12.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2005] [Revised: 12/05/2005] [Accepted: 12/13/2005] [Indexed: 12/11/2022]
Abstract
BACKGROUND Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.
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Affiliation(s)
- V D'Ovidio
- Department of Clinical Sciences, GI Unit, Policlinico Umberto I, University of Rome, La Sapienza, Viale del Policlinico 155, Rome, Italy.
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Cabriada JL, Doménech E, Gomollón F, González-Carro P, González-Lara V, Hinojosa J, Jiménez-López CE, Nos P, Obrador A, Panès J, Saro C, Varea V, Lafuente R, Guilera M. [Consensus document on the use of granulocytapheresis in patients with inflammatory bowel disease]. GASTROENTEROLOGIA Y HEPATOLOGIA 2006; 29:85-92. [PMID: 16448611 DOI: 10.1157/13083905] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
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Yamamoto T, Umegae S, Matsumoto K. Safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis therapy for ulcerative colitis. World J Gastroenterol 2006; 12:520-5. [PMID: 16489663 PMCID: PMC4066082 DOI: 10.3748/wjg.v12.i4.520] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [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. Therefore, removal of activated circulating leukocytes by apheresis has the potential for improving UC. In Japan, since April 2000, leukocytapheresis using Adacolumn has been approved as the treatment for active UC by the Ministry of Health and Welfare. The Adacolumn is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads, and selectively adsorbs granulocytes and monocytes/macrophages. To assess the safety and clinical efficacy of granulocyte and monocyte adsorptive apheresis (GMCAP) for UC, we reviewed 10 open trials of the use of GMCAP to treat UC. One apheresis session (session time, 60 min) per week for five consecutive weeks (a total of five apheresis sessions) has been a standard protocol. Several studies used modified protocols with two sessions per week, with 90-min session, or with a total of 10 apheresis sessions. Typical adverse reactions were dizziness, nausea, headache, flushing, and fever. No serious adverse effects were reported during and after GMCAP therapy, and almost all the patients could complete the treatment course. GMCAP is safe and well-tolerated. In the majority of patients, GMCAP therapy achieved clinical remission or improvement. GMCAP is a useful alternative therapy for patients with steroid-refractory or -dependent UC. GMCAP should have the potential to allow tapering the dose of steroids, and is useful for shortening the time to remission and avoiding re-administration of steroids at the time of relapse. Furthermore, GMCAP may have efficacy as the first-line therapy for steroid-naive patients or patients who have the first attack of UC. However, most of the previous studies were uncontrolled trials. To assess a definite efficacy of GMCAP, randomized, double-blind, sham-controlled trials are necessary. A serious problem with GMCAP is cost; a single session costs ¥145 000 ($1 300). However, if this treatment prevents hospital admission, re-administration of steroids and surgery, and improves a quality of life of the patients, GMCAP may prove to be cost-effective.
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Sawada K, Kusugami K, Suzuki Y, Bamba T, Munakata A, Hibi T, Shimoyama T. Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment. Am J Gastroenterol 2005; 100:1362-9. [PMID: 15929771 DOI: 10.1111/j.1572-0241.2005.41089.x] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Leukocytapheresis (LCAP) is a method of therapeutic apheresis that removes peripheral leukocytes. Previous studies showed that in patients with ulcerative colitis (UC), LCAP was more effective than high-dose steroid therapy, and it had few adverse effects. We investigated LCAP in a multicenter study using active and sham devices in a double-blind study in order to elucidate the placebo effect of extracorporeal treatment including anticoagulant medication. METHODS Twenty-five patients with active UC of severe or moderately severe grade were enrolled and assigned to the active group or the sham group. Six patients were excluded from the study and 19 (10 in the active group and nine in the sham group) were evaluated. LCAP (treatment using an active device or a sham device) was performed once a week for 5 wk, followed by two additional sessions during the next 4 wk at 2-wk intervals. Steroids and other medications were continued at the same dosage for 4 wk, which included a 2-wk pre-observation period and the first 2 wk after the start of the LCAP treatment. New medications or increase in the dosage of previous medication were prohibited until evaluation was conducted. RESULTS The clinical activity index (CAI) value of UC, indicated that the active group showed a significantly greater improvement (80%, 8/10) than the sham group (33%, 3/9; p<0.05). Adverse effects were observed in five patients (one in the active group and four in the sham group). None of these effects was severe and none of the sessions was terminated as a consequence of the adverse effects. CONCLUSION The results confirmed that LCAP is a safe and effective therapeutic option for patients with active UC.
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Affiliation(s)
- Koji Sawada
- Department of Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan
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Kawasaki Y, Suzuki J, Suzuki S, Suzuki H. Leukocytapheresis with leukocyte removal filter for severe ulcerative colitis in childhood. J Pediatr Gastroenterol Nutr 2004; 39:422-5. [PMID: 15448435 DOI: 10.1097/00005176-200410000-00021] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Affiliation(s)
- Yukihiko Kawasaki
- Department of Pediatrics, Fukushima Medical University School of Medicine, Fukushima, Japan.
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Abstract
PURPOSE OF THIS REVIEW The prevalence of early-onset inflammatory bowel disease has been on the rise, with children and adolescents currently accounting for approximately 30% of all patients with this condition. Remarkable new advances in diagnostic modalities and therapy for adults with inflammatory bowel disease, and further information about the role of genetics in determining susceptibility to disease make the review of the recent literature in pediatric inflammatory bowel disease more timely than ever. RECENT FINDINGS In the area of genetics, new studies provide strong evidence for genetic susceptibility to disease, and match genotype with phenotypic presentation. A few studies examine the use of noninvasive diagnostic modalities, such as MRI, and biomarkers (fecal lactoferrin) in pediatric inflammatory bowel disease. Remarkable new agents in therapy for adults with inflammatory bowel disease have been empirically administered to children with inflammatory bowel disease. The first attempts to systematically study the effects of these agents in children and adolescents are reviewed here. Furthermore, new studies revise our notion of surgical outcomes in pediatric inflammatory bowel disease. SUMMARY Although premature for clinical practice application, the role of genetic testing in determining disease susceptibility and assisting with prognosis and course of therapy is clearly evolving and needs further study. As new therapeutic agents join the available treatments of inflammatory bowel disease it is imperative to include pediatric patients in clinical trials. The goals of future studies will be to alter the natural history of early-onset inflammatory bowel disease, reduce the frequency of recurrences, and perhaps reduce requirements for surgical intervention.
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Affiliation(s)
- Helen M Pappa
- Center for Inflammatory Bowel Disease, Division of Gastroenterology and Nutrition, Department of Medicine, Children's Hospital Boston, Massachusetts 02115, USA
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Affiliation(s)
- P Premehand
- Dept. of Gastroenterology, King's College Hospital, London, UK.
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Bremner AR, Griffiths DM, Beattie RM. Current therapy of ulcerative colitis in children. Expert Opin Pharmacother 2004; 5:37-53. [PMID: 14680434 DOI: 10.1517/14656566.5.1.37] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis presents in childhood in 10% of those affected, usually with pancolitis. Important features in management include growth, development and avoidance of treatment toxicity. This review addresses the current treatment options including both the paediatric evidence-based experience and areas where paediatric practice is informed by adult studies. Standard treatments include sulfasalazine or 5-aminosalicylates, corticosteroids, purine derivatives (azathioprine or 6-mercaptopurine) and surgery. Other immunosuppressant therapies and the emerging roles for biological therapies and probiotics are discussed.
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Affiliation(s)
- Alan Ronald Bremner
- Division of Infection, Inflammation and Repair, University of Southampton Medical School, South Academic Block (Mailpoint 813), Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, UK.
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