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Hamasaki Y, Matsuura R, Shinagawa T, Ishihara S, Ihara S, Fujishiro M, Doi K, Nangaku M. Higher Processed Blood Volume of Granulocyte and Monocyte Adsorption Apheresis Ameliorates Long-Term Disease Activity in Ulcerative Colitis Patients. J Clin Med Res 2024; 16:625-634. [PMID: 39759489 PMCID: PMC11699867 DOI: 10.14740/jocmr6071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 12/09/2024] [Indexed: 01/07/2025] Open
Abstract
Background Granulocyte and monocyte adsorption apheresis (GMA) is a therapeutic option for remission induction in the active ulcerative colitis (UC) patients. Effects of high processed blood volume of GMA as remission induction therapy on the long-term prognosis of UC patients have remained unclear. For this study, we investigated the relation between re-exacerbation of UC and the processed blood volume of GMA performed as induction therapy. Methods Data from UC patients treated using a total of 10 GMA sessions as remission induction therapy during 2012 - 2022 were retrospectively collected and analyzed. The relation between the GMA dose, processed blood volume of GMA divided by body weight, and UC re-exacerbation requiring inpatient treatment within 1 year was evaluated. Results This study examined data of 72 active UC patients, with median age of 44.4 years (65% male) and median GMA dose of 34.2 mL/kg/session. Kaplan-Meier analysis showed the 1-year exacerbation-free rate was significantly higher in the higher GMA dose group than in the lower GMA dose group (P = 0.008). Cox proportional hazards regression analyses revealed a higher GMA dose as inversely associated with the re-exacerbation of UC within 1 year (hazard ratio: 0.36, 95% confidence interval: 0.17 - 0.78). Extended treatment time of GMA session beyond 60 min contributed to achieving the higher GMA dose and did not increase unexpected treatment termination because of clotting. Conclusion Greater processed blood volume of GMA per patient body weight may be associated with a lower 1-year exacerbation rate in UC patients.
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Affiliation(s)
- Yoshifumi Hamasaki
- Department of Hemodialysis and Apheresis, The University of Tokyo Hospital, Tokyo, Japan
| | - Ryo Matsuura
- Department of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan
| | | | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Sozaburo Ihara
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kent Doi
- Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital, Tokyo, Japan
| | - Masaomi Nangaku
- Department of Hemodialysis and Apheresis, The University of Tokyo Hospital, Tokyo, Japan
- Department of Nephrology and Endocrinology, The University of Tokyo Hospital, Tokyo, Japan
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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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Rodríguez-Lago I, Cañete F, Guerra-Del-Río E, Herrera-deGuise C, Iglesias E, Leo E, Zabana Y, Barreiro-de Acosta M, Ginard D, Cabriada JL. Combination of granulocyte-monocyte apheresis and tofacitinib: Multicentre and retrospective study. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:727-733. [PMID: 38266817 DOI: 10.1016/j.gastrohep.2024.01.004] [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: 08/29/2023] [Revised: 01/04/2024] [Accepted: 01/18/2024] [Indexed: 01/26/2024]
Abstract
OBJECTIVE Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in treating ulcerative colitis (UC), also in combination with biologics. The objective of this study is to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to tofacitinib (TOFA) in patients with UC. PATIENTS AND METHODS Retrospective study including all patients with refractory UC who received GMA plus TOFA. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS Twelve patients were included (median 46 years [IQR, 37-58]; 67% female; 67% E3). Patients were mostly receiving TOFA 10mg bid (75%), and 33% also concomitant steroids at baseline. Median partial Mayo score at baseline was 7 (IQR, 5-7), and it decreased to a median of 2 (IQR, 0-3) and 0 (IQR, 0-3) after 1 and 6 months (p=0.027 and 0.020, respectively), while no differences were found in CRP and FC. Clinical remission was achieved by 6 patients both at 1 (50%) and 6 months (67%). CF values<250mg/kg were achieved by 2 and 4 patients at 1 and 6 months (data available in 5 and 7 patients, respectively). No patient required dose-escalation of TOFA, and one patient was able to de-escalate the drug. No patient required colectomy and all patients under steroids were able to stop them. CONCLUSION The combination of GMA and TOFA can be effective in selected cases of UC after PNR or LOR to this drug.
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Affiliation(s)
- Iago Rodríguez-Lago
- Gastroenterology Department, Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain.
| | - Fiorella Cañete
- Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain
| | - Elena Guerra-Del-Río
- Gastroenterology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas, Spain
| | | | - Eva Iglesias
- Gastroenterology Department, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Eduardo Leo
- Gastroenterology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain
| | - Yamile Zabana
- Gastroenterology Department, Hospital Universitari Mútua Terrassa, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Terrassa, Spain
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Daniel Ginard
- Gastroenterology Department, Hospital Universitario Son Espases, Palma, Spain
| | - José Luis Cabriada
- Gastroenterology Department, Hospital Universitario de Galdakao, Biobizkaia Health Research Institute, Galdakao, Spain
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Rodríguez-Lago I, Abecia L, Seoane I, Anguita J, Cabriada JL. An in vitro analysis of the interaction between infliximab and granulocyte-monocyte apheresis. GASTROENTEROLOGIA Y HEPATOLOGIA 2024; 47:347-351. [PMID: 37422185 DOI: 10.1016/j.gastrohep.2023.07.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/10/2023]
Abstract
OBJECTIVE Primary non-response and secondary loss of response to anti-TNF agents are common in inflammatory bowel disease. Increasing drug concentrations are correlated to better clinical response and remission rates. Combination of granulocyte-monocyte apheresis (GMA) with anti-tumor necrosis factor (TNF) agents could be an option in these patients. The objective of our study was to perform an in vitro assay to determine if the GMA device can lead to infliximab (IFX) adsorption. PATIENTS AND METHODS A blood sample was obtained from a healthy control. It was incubated with three concentrations of IFX (3, 6, and 9μg/ml) at room temperature for 10min. At that time, 1ml was collected to determine the IFX concentration. Then, 10ml of each drug concentration was incubated with 5ml of cellulose acetate (CA) beads from the GMA device at 200rpm for 1h at 37°C to simulate physiological human conditions. A second sample of each concentration was collected and IFX levels were determined. RESULTS No statistically significant differences were observed in the IFX levels in the blood samples before and after incubation with the CA beads (p=0.41) and after repeated measurements (p=0.31). Mean change was 3.8μg/ml. CONCLUSIONS The in vitro combination of GMA and IFX did not change the circulating levels of IFX at the three concentrations tested, suggesting that there is no interaction between the drug and the apheresis device in vitro and that they might be safely combined with each other.
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Affiliation(s)
- Iago Rodríguez-Lago
- Gastroenterology Department, Hospital Universitario de Galdakao, Biocruces Bizkaia HRI, Galdakao, Spain.
| | - Leticia Abecia
- CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Science and Technology Park, Derio, Spain; Immunology, Microbiology and Parasitology Department, Faculty of Medicine and Nursery School, University of the Basque Country, UPV/EHU, Bilbao, Spain
| | - Iratxe Seoane
- CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Science and Technology Park, Derio, Spain; Immunology, Microbiology and Parasitology Department, Faculty of Medicine and Nursery School, University of the Basque Country, UPV/EHU, Bilbao, Spain
| | - Juan Anguita
- CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bizkaia Science and Technology Park, Derio, Spain; Ikerbasque, Basque Foundation for Science, Bilbao, Spain
| | - José Luis Cabriada
- Gastroenterology Department, Hospital Universitario de Galdakao, Biocruces Bizkaia HRI, Galdakao, Spain
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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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Noguchi Y, Shimazu K, Totani T, Komura K, Tanaka A. Comparison of adsorption efficiency of leukocytes in single needle GMA with or without PSL treatment in patients with active ulcerative colitis. Transfus Apher Sci 2022; 62:103581. [PMID: 36167614 DOI: 10.1016/j.transci.2022.103581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/13/2022] [Accepted: 09/19/2022] [Indexed: 11/15/2022]
Abstract
Granulocyte monocyte adsorption (GMA) is considered one of the modalities for the remission induction of ulcerative colitis (UC). We previously reported that single-needle GMA (SN-GMA) could simplify the GMA. In the present study, the efficiency of SNGMA was examined according to the administration of corticosteroids (PSL) in UC patients. Blood sample were taken at proximal and distal side of the column during the SN-GMA treatment. Disease activity score (partial Mayo score: pMayo score) before and after the SN-GMA was investigated. The data of 18 patients with active UC (11 and 7 patients with PSL naïve and PSL use groups, respectively) treated with SN-GMA was analyzed. The mean pMayo score before the GMA treatment was comparable between the PSL naïve group (p = 0.26), whereas the score after the GMA treatment was significantly lower in PSL naïve group (0.8 + 0.6) than in PSL use group (3.0 + 2.1) (p = 0.04). Patients achieving the clinical remission were more observed in the PSL naive group (90.9%) than in the PSL use group (42.9%) (p = 0.047). The adsorption efficiency in the PSL naïve and PSL use groups were as follows: leukocytes (34.45 ± 7.43% vs 23.14 ± 7.56%: p = 0.008), granulocytes (41.74 ± 10.07% vs 27.99 ± 15.11%: p = 0.04), monocytes (32.59 ± 24.07% vs 33.16 ± 24.18%: p = 0.95), and lymphocytes (-1.87 ± 18.17% vs -3.79 ± 22.52%: p = 0.84), with a significant difference of the absorption efficiency in leukocytes and granulocytes. These data collectively indicate that the SN-GMA can be applied for the remission induction to active UC patients with a higher clinical remission rate in PSL naïve patients compared to PSL use patients.
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Affiliation(s)
- Yuki Noguchi
- Department of Clinical Engineering Technology, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-ku, Osaka City, Osaka 530-0012, Japan
| | - Keiji Shimazu
- Department of Nephrology, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-ku, Osaka City, Osaka 530-0012, Japan
| | - Teruhiko Totani
- Department of Clinical Engineering Technology, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-ku, Osaka City, Osaka 530-0012, Japan
| | - Kazumasa Komura
- Department of Urology, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka 569-8686, Japan.
| | - Atsuo Tanaka
- Department of Nephrology, Osaka Saiseikai Nakatsu Hospital, 2-10-39 Shibata, Kita-ku, Osaka City, Osaka 530-0012, Japan
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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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Rodríguez-Lago I, Benítez JM, Sempere L, Sáez-González E, Barreiro-de Acosta M, de Zárate JO, Cabriada JL. The combination of granulocyte-monocyte apheresis and vedolizumab: A new treatment option for ulcerative colitis? J Clin Apher 2019; 34:680-685. [PMID: 31518013 DOI: 10.1002/jca.21746] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Revised: 08/27/2019] [Accepted: 08/29/2019] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To assess the effectiveness and safety of combining granulocyte-monocyte apheresis (GMA) and vedolizumab (VDZ) in patients with refractory ulcerative colitis (UC). METHODS This retrospective, multicentre pilot study included all UC patients receiving both GMA and VDZ. We recorded data on GMA sessions, demographic characteristics, and clinical response. Effectiveness was assessed 1 and 6 months after finishing the GMA using the partial Mayo score, C-reactive protein, and fecal calprotectin levels. Data were also compiled on VDZ intensification, use of new immunomodulators and colectomy during follow-up. RESULTS Eight patients were included (mean age 46 years; 63% female; mean disease duration, 132 months; 50% E3). GMA was started after a loss of response to VDZ in all cases (25% primary nonresponse and 75% secondary loss of response). All had previously received anti-TNF agents. VDZ was prescribed as the second-, third-, or fourth-line biologic in 37%, 50%, and 13% of cases, respectively. Patients had a mean baseline partial Mayo score of 7.5 (SD 2.1) and received a median of 15 GMA sessions (range 5-38). After a median follow-up of 7.5 months (IQR 5-12), partial Mayo score decreased after 1 and 6 months (P = .01 and .06, respectively). Three patients (38%) achieved steroid-free clinical remission and five (63%) withdrew VDZ. Colectomy rate was 38%. No adverse events were observed during the combination therapy. CONCLUSIONS This small case series suggests that combining GMA with VDZ could be a treatment option in selected cases of UC with an inadequate response to this biologic agent.
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Affiliation(s)
- Iago Rodríguez-Lago
- Gastroenterology Department, Hospital de Galdakao, Galdakao, Spain.,Biocruces Bizkaia Health Research Institute, Barakaldo, Vizcaya, Spain
| | - José M Benítez
- Gastroenterology Department, Hospital Universitario Reina Sofía, Córdoba, Spain.,IMIBIC, Córdoba, Spain
| | - Laura Sempere
- Gastroenterology Department, Hospital General Universitario de Alicante, Alicante, Spain
| | - Esteban Sáez-González
- Gastroenterology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
| | - Manuel Barreiro-de Acosta
- Gastroenterology Department, Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Jone O de Zárate
- Gastroenterology Department, Hospital Universitario de Basurto, Bilbao, Spain
| | - José L Cabriada
- Gastroenterology Department, Hospital de Galdakao, Galdakao, Spain.,Biocruces Bizkaia Health Research Institute, Barakaldo, Vizcaya, Spain
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Okuno T, Yoshida Y, Takaki Y, Araki Y, Inoue H, Soejima K, Okado Y, Yoshida K, Imamura H, Hagiwara S, Matsumoto S, Kitano T. Observation of Granulocyte Adsorption in Adacolumn Cellulose Acetate Beads after Granulocytapheresis. Ther Apher Dial 2019; 23:210-216. [PMID: 31025504 DOI: 10.1111/1744-9987.12815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 12/18/2018] [Indexed: 11/28/2022]
Abstract
Adacolumn is a therapeutic mode for ulcerative colitis that achieves therapeutic efficacy through the adhesion of leukocytes to cellulose acetate beads. We used scanning electron microscopy and observed leukocyte adsorption on Adacolumn beads after granulocytapheresis/granulocyte and monocyte adsorption apheresis. We then compared results between two patients with a low and high C-reactive protein (CRP) levels to determine whether adhesion is affected by a difference in leukocyte activity depending on the level of inflammation. We found that the surface layers of the beads from both patients were covered by a clay-like layer, and spherical granulocytes were adsorbed here and there on top of it. In cross-section the adsorbed granulocytes were visible in the clay-like layer and the surface layer alike. The clay-like layer had a maximum thickness of approximately 12 μm in the low CRP patient and approximately 50 μm in the high CRP patient, so in the high CRP patient the clay-like adsorption layer was thicker. Taken together, adsorption onto beads is considered to involve an immunological mechanism. Our findings suggest that granulocytes contact and adhere to each other at the surface layer after adsorption, and that granulocyte-granulocyte adhesion is enhanced by a higher inflammatory response.
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Affiliation(s)
- Toshiyuki Okuno
- Department of Clinical Engineering, Saiseikai Kumamoto Hospital, Kumamoto, Japan.,Graduate School of Medicine, Oita University, Oita, Japan
| | - Yutaka Yoshida
- Department of Clinical Engineering, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Yuriko Takaki
- Department of Clinical Engineering, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Yasuyuki Araki
- Department of Clinical Engineering, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Hironobu Inoue
- Division of Nephrology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Kazuaki Soejima
- Department of Clinical Engineering, Saiseikai Kumamoto Hospital, Kumamoto, Japan.,Division of Nephrology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Yuki Okado
- Division of Gastroenterology & Hepatology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Kenichi Yoshida
- Division of Gastroenterology & Hepatology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | - Haruo Imamura
- Division of Gastroenterology & Hepatology, Saiseikai Kumamoto Hospital, Kumamoto, Japan
| | | | - Shigekiyo Matsumoto
- Department of Anesthesiology, Faculty of Medicine, Oita University, Oita, Japan
| | - Takaaki Kitano
- Department of Anesthesiology, Faculty of Medicine, Oita University, Oita, 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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Domènech E, Panés J, Hinojosa J, Annese V, Magro F, Sturniolo GC, Bossa F, Fernández F, González-Conde B, García-Sánchez V, Dignass A, Herrera JM, Cabriada JL, Guardiola J, Vecchi M, Portela F, Ginard D. Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial. J Crohns Colitis 2018; 12:687-694. [PMID: 29490024 DOI: 10.1093/ecco-jcc/jjy023] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 02/26/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. METHODS This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. RESULTS In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. CONCLUSIONS In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.
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Affiliation(s)
- Eugeni Domènech
- Hospital Universitari Germans Trias i Pujol, Badalona, Spain, and CIBEREHD, Madrid, Spain
| | - Julián Panés
- Hospital Clínic, Barcelona, Spain and CIBEREHD, Madrid, Spain
| | | | | | - Fernando Magro
- Unit of Pharmacology and Therapeutics, Faculty of Medicine; MedInUP, Centre for Drug Discovery and Innovative Medicines, University of Porto, Porto, Portugal
| | | | | | | | | | - Valle García-Sánchez
- Hospital Universitario Reina Sofía amd IMIBIC, Córdoba, Spain, and CIBEREHD, Madrid, Spain
| | - Axel Dignass
- Charité-Campus Virchow Klinikum, Berlin, Germany
| | | | | | - Jordi Guardiola
- Hospital Universitari de Bellvitge, L'Hospitalet del Llobregat, Spain
| | - Maurizio Vecchi
- Department of Biomedical Science for the Health, University of Milan, and IRCCS Policlinico San Donato, Milano, Italy
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Granulocyte and monocyte apheresis in inflammatory bowel disease: The patients' point of view. GASTROENTEROLOGIA Y HEPATOLOGIA 2018; 41:423-431. [PMID: 29739692 DOI: 10.1016/j.gastrohep.2018.04.007] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2018] [Revised: 04/04/2018] [Accepted: 04/06/2018] [Indexed: 12/19/2022]
Abstract
BACKGROUND Granulocyte and monocyte apheresis is the main non-pharmacological treatment for inflammatory bowel disease (IBD), but we do not know how well accepted it is by patients in our setting. AIM To determine how granulocyte and monocyte apheresis is perceived by patients in clinical practice in Spain. METHODS Outpatients treated with granulocyte and monocyte apheresis in five IBD Units in Spain were asked to fill in a 14-item questionnaire. RESULTS Fifty-two patients completed the questionnaire (88% ulcerative colitis, 12% Crohn's disease; 44% female; age 35 years [IQR 23-51]). Granulocyte and monocyte apheresis was generally well tolerated and well accepted. Very few of the participants regarded the length of the sessions as a limitation. The gastrointestinal symptoms, however, were a frequent concern, both in terms of attending to receive treatment and during the sessions. Overall, 44% were satisfied with the treatment effectiveness. Sixty percent (60%) claimed to be satisfied with the therapy overall, but this was influenced by the patients' clinical response to the therapy. Eighty-two percent (82%) of participants said they would agree to be treated with this technique again in the future, regardless of the response to the treatment. CONCLUSIONS Granulocyte and monocyte apheresis is well tolerated and accepted by patients with IBD. Although we found no significant differences according to type of IBD or apheresis regimen, patient perception was affected by clinical effectiveness.
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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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Nishise S, Takeda Y, Abe Y, Sasaki Y, Nara H, Asao H, Ueno Y. Effect of Temperature on Granulocyte and Monocyte Adsorption to Cellulose Acetate Beads. Ther Apher Dial 2017; 21:248-254. [DOI: 10.1111/1744-9987.12558] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Affiliation(s)
- Shoichi Nishise
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yuji Takeda
- Department of Immunology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yasuhiko Abe
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yu Sasaki
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Hidetoshi Nara
- Department of Immunology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Hironobu Asao
- Department of Immunology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
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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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Lai Y, Zhang M, Wang L, Yang A, Li J, Zhang X, Zhou X, Hong T, Qian J, Zhong D. Uveitis and T cell lymphoma: a rare but notable relationship. Med Oncol 2014; 31:992. [PMID: 24961468 DOI: 10.1007/s12032-014-0992-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Accepted: 04/28/2014] [Indexed: 11/26/2022]
Abstract
Uveitis is an autoimmune disease of the eye that refers to a number of intraocular inflammatory conditions. We identified three rare cases of T cell lymphoma diagnosed following an initial presentation of uveitis. This study summarized the clinical features of these rare cases and evaluated the association between uveitis and lymphoma. We analyzed the etiology of uveitis diagnosed in the Department of Pediatrics and Internal Medicine at our hospital. Five patients were diagnosed with uveitis and lymphoma. We present case reports of three patients who were diagnosed with T cell lymphoma following an initial presentation of uveitis. From January 1985 to June 2013, there were 80 cases of uveitis and 1,900 cases of lymphoma in the Department of Pediatrics and Internal Medicine at our hospital. We found five patients that were diagnosed with uveitis and lymphoma; of these, three had a definite pathologic diagnosis of T cell lymphoma. The odds ratio (OR) was 6.08 (95 % confidence interval [CI] of 1.93-14.94, P = 0.002) for the five patients with uveitis and lymphoma, suggesting a significant association. The OR was 3.67 (95 % CI of 1.16-11.65, P = 0.053) for the three patients with uveitis and T cell lymphoma. Uveitis may be a rare presentation of malignant disease, such as lymphoma. Ophthalmologists and general practitioners should be familiar with the differential diagnosis of uveitis.
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Affiliation(s)
- Yamin Lai
- Departments of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, No. 1, Shuaifuyuan, Dongcheng District, Beijing, 100730, China
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Nagase K, Fukuanga K, Yokoyama Y, Kamikozuru K, Miwa H, Nakamura S. Questionnaire Based Assessment of Patients' Acceptability of Leukocytapheresis for the Treatment of Inflammatory Bowel Disease. Ther Apher Dial 2013; 17:490-7. [DOI: 10.1111/1744-9987.12115] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Kazuko Nagase
- Department of Internal Medicine; Division of Lower; Hyogo College of Medicine; Nishinomiya Japan
| | - Ken Fukuanga
- Department of Internal Medicine; Division of Lower; Hyogo College of Medicine; Nishinomiya Japan
| | - Yoko Yokoyama
- Department of Internal Medicine; Division of Lower; Hyogo College of Medicine; Nishinomiya Japan
| | - Koji Kamikozuru
- Department of Internal Medicine; Division of Lower; Hyogo College of Medicine; Nishinomiya Japan
| | - Hiroto Miwa
- Division of Upper Gastroenterology; Hyogo College of Medicine; Nishinomiya Japan
| | - Shiro Nakamura
- Department of Internal Medicine; Division of Lower; Hyogo College of Medicine; Nishinomiya Japan
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Yokoyama Y, Kawai M, Fukunaga K, Kamikozuru K, Nagase K, Nogami K, Kono T, Ohda Y, Iimuro M, Hida N, Nakamura S, Miwa H, Matsumoto T. Looking for predictive factors of clinical response to adsorptive granulocyte and monocyte apheresis in patients with ulcerative colitis: markers of response to GMA. BMC Gastroenterol 2013; 13:27. [PMID: 23399416 PMCID: PMC3583683 DOI: 10.1186/1471-230x-13-27] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 02/08/2013] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn in patients with ulcerative colitis (UC) has been applied as a non-pharmacological treatment strategy, but the efficacy has been encouraging as well as discouraging, depending on patients' demography at entry. In this study, we looked for predictive factors for clinical response to GMA in patients with UC. METHODS In a retrospective setting, 43 outpatients who had been treated with GMA for active UC were evaluated. Patients were divided into remission group and non-remission group based on Lichtiger's clinical activity index (CAI) before and after 10, once a week GMA sessions. The efficacy was analysed in relation to patients' demographic variables. To determine predictive factors that closely related to the response to GMA, receiver operating characteristic (ROC) curve, and multiple logistic regression analyses were applied. RESULTS After 10 GMA sessions, the overall clinical remission rate (CAI < 4) was 53.5%. Multiple logistic regression and ROC analyses showed that the interval between relapse and the first GMA session was a significant and independent predictive factor for clinical response to GMA (P = 0.016); the clinical response was better in patients who received GMA immediately after a relapse and vice versa. Likewise, univariate analyses showed that, the duration of UC (P = 0.036) and the cumulative prednisolone (PSL) dose (P = 0.006) before the first GMA session were significantly greater in the GMA non-responder group as compared with the responder group. Additionally, a lower white blood cell (WBC) count at first GMA session was related to clinical response to GMA (P = 0.032). CONCLUSIONS In this study, patients with a short duration of UC and low cumulative PSL dose seemed to respond well to GMA. However, we found that the best responders were patients who received GMA immediately after a clinical relapse. Additionally, GMA was effective in patients with low WBC count at the first GMA session. The findings of this study should spare medical cost and reduce morbidity time for many patients, relevant for decision making in clinical settings.
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Affiliation(s)
- Yoko Yokoyama
- Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa, Nishinomiya, 663-8501, Hyogo, Japan.
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Winters JL. Randomized controlled trials in therapeutic apheresis. J Clin Apher 2013; 28:48-55. [DOI: 10.1002/jca.21263] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2012] [Accepted: 01/15/2013] [Indexed: 12/28/2022]
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Fukunaga K, Matsumoto T. Current status and future perspectives of leukocytapheresis for inflammatory bowel disease. J Gastroenterol Hepatol 2012; 27:997-1003. [PMID: 22414250 DOI: 10.1111/j.1440-1746.2012.07119.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) comprise the idiopathic inflammatory bowel diseases (IBD) of the gut. The etiology of IBD is poorly understood, but an autoimmune disturbance has been suggested to play an important role in this incurable disease. Extracorporeal leukocytapheresis (CAP) is an additional adjunct for IBD patients refractory to other conventional therapies, including steroids. The primary aim of CAP should be to suppress such unwanted immunological response by removing circulating inflammatory cells from the blood stream. The first decade has been passed since CAP was approved by Japanese social health insurance policy. It is therefore now an appropriate opportunity to upgrade and summarize our current understandings and/or future perspectives of this unique non-pharmacological and non-surgical strategy for IBD patients. According to several clinical and basic research reports, an early introduction of CAP should produce higher efficacy as compared with CAP applied sometime after a clinical relapse. Likewise, CAP therapy adjusted to patients' body-weight as well as two treatment sessions per week (intensive regimen) should benefit the efficacy rate. The etiology of IBD is not fully elucidated yet. As a result, the major therapeutic strategies in the Western world have been immunosuppressive therapy, including biologics. CAP is an unusual treatment modality for IBD because it seems to have both effectiveness and safety, which should generally be balanced in this type of illness. We now have to develop future strategies with and without combining biologics to improve the quality of life of IBD patients.
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Affiliation(s)
- Ken Fukunaga
- Departments of Lower Gastroenterology and Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
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