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Abe N, Higashi Y, Tateishi C, Kanekura T, Tsuruta D, Kobayashi T, Okubo Y. Efficacy of granulocyte and monocyte adsorptive apheresis on skin and joint manifestations of palmoplantar pustulosis with pustulotic arthro-osteitis: A multicentric, prospective, observational study. J Dermatol 2025; 52:642-650. [PMID: 39936375 PMCID: PMC11975200 DOI: 10.1111/1346-8138.17667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 01/20/2025] [Accepted: 01/28/2025] [Indexed: 02/13/2025]
Abstract
Granulocyte and monocyte adsorptive apheresis (GMA) selectively removes activated granulocytes and monocytes from the peripheral blood. In 2012, GMA was approved in Japan as a treatment for generalized pustular psoriasis and localized pustular psoriasis or palmoplantar pustulosis (PPP). Limited evidence from case reports and monocentric studies suggested that GMA is an effective treatment for skin and joint symptoms of PPP with pustulotic arthro-osteitis (PAO). The present, prospective, observational study was performed at three dermatology departments in Japan to evaluate the efficacy and safety of GMA in patients with PPP with PAO. Between April 2017 and December 2020, two male and 12 female patients with PPP and PAO were enrolled. Their mean age, mean duration of skin manifestations, and mean duration of PAO symptoms was 52.8 years, 51.2 months, and 44.9 months, respectively. GMA was applied weekly over five sessions. The skin and joint symptoms were assessed at baseline, post-GMA, and at the 3-month follow-up. A total of 12 patients completed five GMA sessions, and two patients discontinued the treatment because of adverse events. Thus, 12 patients were finally assessed post-GMA, and 10 patients were assessed at the 3-month follow-up. The assessment of GMA efficacy demonstrated that the skin symptoms had remarkably improved and improved in 33.3% (4/12) and 70% (7/10) of the patients post-GMA and at the 3-month follow-up, respectively. Furthermore, the joint symptoms had remarkably improved in 66.7% (8/12) and 60% (6/10) of the patients post-GMA and at the 3-month follow-up, respectively. These results suggest that GMA is effective in treating the skin and joint symptoms of PPP with PAO.
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Affiliation(s)
- Namiko Abe
- Department of DermatologyTokyo Medical UniversityTokyoJapan
| | - Yuko Higashi
- Department of DermatologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Chiharu Tateishi
- Department of DermatologyGraduate School of MedicineOsaka Metropolitan UniversityOsakaJapan
| | - Takuro Kanekura
- Department of DermatologyKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
| | - Daisuke Tsuruta
- Department of DermatologyGraduate School of MedicineOsaka Metropolitan UniversityOsakaJapan
| | | | - Yukari Okubo
- Department of DermatologyTokyo Medical UniversityTokyoJapan
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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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Nishioka Y, Murayama G, Kusaoi M, Takemasa D, Kaneda K, Kuga T, Hagiwara Y, Saito T, Yamaji Y, Suzuki Y, Nagaoka T, Yamaji K, Tamura N. Enhanced therapeutic efficacy of granulocyte/monocyte adsorption in rats with drug-induced colitis : Insights from a downsized bead column and newly formed B cells. Ther Apher Dial 2024. [PMID: 39568103 DOI: 10.1111/1744-9987.14234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 11/06/2024] [Accepted: 11/11/2024] [Indexed: 11/22/2024]
Abstract
INTRODUCTION Granulocyte/monocyte adsorption therapy can manage mild-to-moderate inflammatory bowel disease by removing activated granulocytes and monocytes. We evaluated granulocyte/monocyte adsorption using new columns with reduced bead size and theoretically enhanced adsorption. METHODS We assessed granulocyte/monocyte adsorption in rats with colitis by analyzing cell changes and cytokine production. RESULTS Granulocyte/monocyte adsorption with the new columns improved histology in rats with colitis. Contrary to expectations, the adsorption rate of granulocytes/monocytes into the blood did not show a significant improvement. However, flow cytometry showed increased B cells in peripheral blood mononuclear cells and newly formed B cells in the bone marrow, which produced more interleukin-10 than peripheral blood B cells. Newly formed B cells adoptively transferred into colitis rats accumulated at the inflammation site and tended to inhibit intestinal shortening. CONCLUSIONS Newly formed B cells with strong interleukin-10 production may alleviate inflammation. The new columns suggest potential for controlling colitis.
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Affiliation(s)
- Yujin Nishioka
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Goh Murayama
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Makio Kusaoi
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | | | | | - Taiga Kuga
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yukitomo Hagiwara
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Takumi Saito
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yu Yamaji
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Yoshifumi Suzuki
- Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Tetsutaro Nagaoka
- Department of Respiratory Medicine, Juntendo University School of Medicine, Tokyo, Japan
| | - Ken Yamaji
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, Tokyo, Japan
| | - Naoto Tamura
- Department of Internal Medicine and Rheumatology, Juntendo University School of Medicine, 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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Tanida S, Sasoh S, Otani T, Kubota Y, Ban T, Ando T, Nakamura M, Joh T. Efficacy and Safety of Upadacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction for Intractable Ulcerative Colitis. J Clin Med Res 2024; 16:256-263. [PMID: 38855784 PMCID: PMC11161188 DOI: 10.14740/jocmr5165] [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: 03/25/2024] [Accepted: 04/26/2024] [Indexed: 06/11/2024] Open
Abstract
Monotherapy with a selective Janus kinase (JAK) inhibitor or intensive granulocyte and monocyte adsorptive apheresis (GMA) has been limited to patients with intractable ulcerative colitis (UC). No previous reports have described the efficacy including histopathological evaluations and the safety of combination therapy with upadacitinib (UPA) plus intensive GMA (two sessions per week) for intractable UC showing resistance to conventional agents and adalimumab. This retrospective study evaluated the 10-week clinical and histopathological efficacy of induction combination therapy with UPA plus intensive GMA in patients with intractable UC. Among eight patients (moderate UC, n = 1; severe UC, n = 7) who received combination therapy with UPA plus intensive GMA, 50.0% had achieved clinical remission by 10 weeks. Percentages of patients with histological-endoscopic mucosal improvement and mucosal healing at 10 weeks were 62.5% and 12.5%, respectively. After excluding one patient who discontinued treatment by week 10 because of intolerance for UPA, mean full Mayo score, endoscopic subscore and C-reactive protein concentration at baseline were 11.43 ± 0.37, 3 ± 0 and 1.29 ± 0.70 mg/dL, respectively. Corresponding values at 10 weeks were 2.28 ± 0.77 (P < 0.03), 1.14 ± 0.34 (P < 0.03) and 0.03 ± 0.008 mg/dL (P < 0.05), respectively. Adverse events of herpes zoster, temporary increase in creatinine phosphokinase and anemia were observed in one patient each. One patient discontinued combination therapy at week 4 because of temporary taste abnormality due to UPA. Combination comprising UPA plus intensive GMA appears likely to achieve satisfactory induction of clinical remission and histopathological improvement for patients with intractable UC for whom conventional agents and anti-tumor necrosis factor-α antibody have failed.
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Affiliation(s)
- Satoshi Tanida
- Education and Research Center for Community Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
| | - Shun Sasoh
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
| | - Takahiro Otani
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
| | - Yoshimasa Kubota
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
| | - Tesshin Ban
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
| | - Tomoaki Ando
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
| | - Makoto Nakamura
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
| | - Takashi Joh
- Division of Gastroenterology, Gamagori City Hospital, Gamagori 443-8501, Japan
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Ito A, Murasugi S, Yonezawa M, Omori T, Nakamura S, Tokushige K. A retrospective study to investigate the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis with ulcerative colitis. J Clin Apher 2024; 39:e22099. [PMID: 37990778 DOI: 10.1002/jca.22099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 09/24/2023] [Accepted: 11/07/2023] [Indexed: 11/23/2023]
Abstract
BACKGROUND AND AIMS Primary sclerosing cholangitis has a poor prognosis and can be accompanied by ulcerative colitis. Infection control is essential, so immunosuppressive drugs should ideally be preferably. Granulocyte and monocyte adsorptive apheresis does not suppress the immune system and is used to treat ulcerative colitis. Therefore, this study investigated the efficacy and safety of granulocyte and monocyte adsorptive apheresis in patients with primary sclerosing cholangitis and ulcerative colitis. METHODS We retrospectively evaluated data from patients with primary sclerosing cholangitis with ulcerative colitis who visited our hospital from April 2000 to December 2022 and underwent granulocyte and monocyte adsorptive apheresis (n = 10, number of treatment cycles = 15). Study endpoints were remission induction rate and safety, assessed as changes in liver functions and adverse events. RESULTS Seven of the 10 patients were male. The median (min-max) age was 23 (18-77) years. The most common disease type was right-dominant pancolitis. Remission occurred after 86.6% of cycles (13/15). Serum alkaline phosphatase and Aspartate transaminase were significantly lower after treatment (P = .0124, P = .002), and no negative effects on liver function were seen. The only adverse events were headache (n = 1) and decreased blood pressure (n = 1). CONCLUSIONS Granulocyte and monocyte adsorptive apheresis has high efficacy for intestinal lesions and improves alkaline phosphatase and aspartate transaminase levels (high levels are a poor prognosis factor). It appears to be a treatment option in patients with primary sclerosing cholangitis associated with ulcerative colitis.
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Affiliation(s)
- Ayumi Ito
- Department of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shun Murasugi
- Department of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Maria Yonezawa
- Department of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Teppei Omori
- Department of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Shinichi Nakamura
- Department of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
| | - Katsutoshi Tokushige
- Department of Gastroenterology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan
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Vernia F, Viscido A, Latella G. Adsorptive cytapheresis in ulcerative colitis: A non-pharmacological therapeutic approach revisited. J Clin Apher 2023; 38:746-754. [PMID: 37787399 DOI: 10.1002/jca.22091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Revised: 09/03/2023] [Accepted: 09/14/2023] [Indexed: 10/04/2023]
Abstract
Adsorptive cytapheresis proves effective in a proportion of patients affected by ulcerative colitis. Relatively high cost and the need for apheresis facilities, prevented the widespread use of this therapeutic approach. More so following the introduction of anti-TNFα biosimilars which proved both effective and inexpensive. Anti-TNFα agents, however, are burdened by high rate of primary and secondary non-response and prompt switching to new, high-cost biologics, and small molecules. The present review analyzes advantages and disadvantages of adsorptive cytapheresis in the present clinical scenario and suggests its repositioning in the therapeutic workup of selected subgroups of ulcerative colitis patients. The extremely favorable safety profile makes adsorptive cytapheresis a viable therapeutic option in elderly and high-risk UC patients, as well as potential second-line treatment in corticosteroid-dependent patients and poor responders to first-line biologics.
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Affiliation(s)
- Filippo Vernia
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Angelo Viscido
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Giovanni Latella
- Gastroenterology Unit, Division of Gastroenterology, Hepatology, and Nutrition, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
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Jin H, Park SK, Yun YG, Song NE, Baik SH. Isolation of Latilactobacillus curvatus with Enhanced Nitric Oxide Synthesis from Korean Traditional Fermented Food and Investigation of Its Probiotic Properties. Microorganisms 2023; 11:2285. [PMID: 37764128 PMCID: PMC10536857 DOI: 10.3390/microorganisms11092285] [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: 08/21/2023] [Revised: 08/31/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Nitric oxide (NO) is a free radical associated with physiological functions such as blood pressure regulation, cardiovascular health, mitochondrial production, calcium transport, oxidative stress, and skeletal muscle repair. This study aimed to isolate Latilactobacillus curvatus strains with enhanced NO production from the traditional Korean fermented food, jangajji, and evaluate their probiotic properties for industrial purposes. When cells were co-cultured with various bacterial stimulants, NO production generally increased, and NO synthesis was observed in the range of 20-40 mg/mL. The selected strains of Lat. curvatus were resistant to acid and bile conditions and with variable effectiveness (1-14%) in adhering to Caco-2 cells. Most bacterial strains can inhibit the growth of various pathogens. In addition, they are capable of reducing cholesterol levels via assimilation of cholesterol at 10-50%. Among the selected NO synthases from Lat. curvatus strains, the strain JBCC38 showed the highest capacity to scavenge ABTS (30.1%) and DPPH radicals (39.4%). Moreover, these strains exhibited immunomodulatory properties. The production of TNF-α and IL-6 in the macrophages treated with various bacterial stimulants was induced in all the selected strains.
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Affiliation(s)
| | | | | | | | - Sang-Ho Baik
- Department of Food Science and Human Nutrition, Jeonbuk National University, Jeonju 54896, Republic of Korea; (H.J.); (S.-K.P.); (Y.-G.Y.); (N.-E.S.)
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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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Bamias G, Zampeli E, Domènech E. Targeting neutrophils in inflammatory bowel disease: revisiting the role of adsorptive granulocyte and monocyte apheresis. Expert Rev Gastroenterol Hepatol 2022; 16:721-735. [PMID: 35833363 DOI: 10.1080/17474124.2022.2100759] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract comprising Crohn's disease (CD) and ulcerative colitis (UC). While any part of the digestive tract can be affected in CD, mucosal inflammation in UC is limited to the colon. Differences and similarities between the two conditions are reflected by their pathophysiology. AREAS COVERED An overview of immunological aspects, pharmacological management, and biomarkers of IBD is provided. The role of adsorptive granulocyte and monocyte apheresis (GMA) is reviewed including its primary and secondary effects on the immune system, as well as clinical studies in IBD (mainly UC), and potential biomarkers for adsorptive GMA. EXPERT OPINION In UC, adsorptive GMA with Adacolumn (Adacolumn®, JIMRO Co., Ltd. Takasaki, Gunma, Japan) selectively depletes elevated myeloid lineage leukocytes and has a range of beneficial secondary immune effects. Adsorptive GMA is a safe and effective non-pharmacological treatment option for UC. Pilot studies have reported promising results for adsorptive GMA in combination with biological agents, although larger studies are required. Fecal calprotectin concentrations, neutrophil counts in histological samples and/or the neutrophil/lymphocyte ratio in peripheral blood may prove to be useful biomarkers for predicting GMA effectiveness in the future.
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Affiliation(s)
- Giorgos Bamias
- GI-Unit, 3rd Department of Internal Medicine National and Kapodistrian University of Athens, Sotiria Hospital, Athens, Greece
| | - Evanthia Zampeli
- Gastroenterology Department, Alexandra General Hospital, Athens, Greece
| | - Eugeni Domènech
- Gastroenterology Department, Hospital Universitari Germans Trias I Pujol, Badalona, Catalonia, Spain, and Centro de Investigación Biomédica En Red de Enfermedades Hepáticas Y Digestivas (CIBEREHD), Madrid, Spain
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Domènech E, Grífols JR, Akbar A, Dignass AU. Use of granulocyte/monocytapheresis in ulcerative colitis: A practical review from a European perspective. World J Gastroenterol 2021; 27:908-918. [PMID: 33776362 PMCID: PMC7968132 DOI: 10.3748/wjg.v27.i10.908] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/03/2021] [Accepted: 02/11/2021] [Indexed: 02/06/2023] Open
Abstract
Half of the patients with ulcerative colitis require at least one course of systemic corticosteroids in their lifetime. Approximately 75% of these patients will also require immunosuppressive drugs (i.e., thiopurines or biological agents) in the mid-term to avoid colectomy. Immunosuppressive drugs raise some concerns due to an increased risk of serious and opportunistic infections and cancer, particularly in elderly and co-morbid patients, underlining the unmet need for safer alternative therapies. Granulocyte/monocytapheresis (GMA), a CE-marked, non-pharmacological procedure for the treatment of ulcerative colitis (among other immune-mediated diseases), remains the only therapy targeting neutrophils, the hallmark of pathology in ulcerative colitis. GMA has proven its efficacy in different clinical scenarios and shows an excellent and unique safety profile. In spite of being a first line therapy in Japan, GMA use is still limited to a small number of centres and countries in Europe. In this article, we aim to give an overview from a European perspective of the mechanism of action, recent clinical data on efficacy and practical aspects for the use of GMA in ulcerative colitis.
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Affiliation(s)
- Eugeni Domènech
- Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Catalonia, Spain
- Department of Medicine, Universitat Autònoma de Barcelona, Badalona 08916, Catalonia, Spain
- Centro de Investigaciones Biomédicas en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Badalona 08916, Catalonia, Spain
| | - Joan-Ramon Grífols
- Blood and Tissue Bank, Hospital Universitari Germans Trias i Pujol, Badalona 08916, Catalonia, Spain
| | - Ayesha Akbar
- IBD Unit, St. Mark’s Hospital and Academic Institute, London HA1 3UJ, United Kingdom
| | - Axel U Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe-University, Frankfurt am Main 60431, Germany
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12
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Yamamoto T. Similarity and difference between palmoplantar pustulosis and pustular psoriasis. J Dermatol 2021; 48:750-760. [PMID: 33650702 DOI: 10.1111/1346-8138.15826] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 02/07/2021] [Indexed: 12/11/2022]
Abstract
Palmoplantar pustulosis is a chronic inflammatory disorder characterized by sterile pustules predominantly involving the palms and soles. Palmoplantar pustulosis has many similar aspects to psoriasis, either plaque and pustular type, namely familial occurrence between palmoplantar pustulosis and psoriasis, the appearance of the Köbner phenomenon, joint involvement, and nail involvement. Pustular psoriasis is classified into generalized and localized types, and there are a number of papers regarding palmoplantar pustulosis as an acral variant of localized pustular psoriasis. Many Japanese dermatologists consider palmoplantar pustulosis to be a distinct entity from pustular psoriasis, and the coexistence of palmoplantar pustulosis and psoriasis is rare. However, outside Japan, palmoplantar pustulosis is often considered to be palmoplantar psoriasis or palmoplantar pustular psoriasis, and extra-palmoplantar lesions are also considered to be psoriasis. The purpose of the current review is to compare the similarities and differences between palmoplantar pustulosis and generalized/localized pustular psoriasis. Japanese patients with palmoplantar pustulosis have a close relationship with focal infection, and the associated bone-joint manifestation exclusively involves the anterior chest wall. Furthermore, pediatric occurrence of palmoplantar pustulosis is extremely rare, and difference of genetic background between palmoplantar pustulosis and psoriasis has also been reported. Treatment of focal infection often results in dramatic effects on both cutaneous lesions and joint pain of palmoplantar pustulosis. Those findings suggest that palmoplantar pustulosis should be separately considered from either palmoplantar psoriasis or palmoplantar pustular psoriasis. The clinicopathological features and therapeutic approach of both diseases are discussed.
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Affiliation(s)
- Toshiyuki Yamamoto
- Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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13
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Kakimoto K, Matsuura M, Fukuchi T, Hongo H, Kimura T, Aoyama N, Okuda Y, Aomatsu K, Kamata N, Yokoyama Y, Mizuno C, Inoue T, Miyazaki T, Nakamura S, Higuchi K, Nakase H. Exploratory Study of the Effectiveness of Granulocyte and Monocyte Adsorptive Apheresis Before Initiation of Steroids in Patients With Active Ulcerative Colitis (EXPECT Study): A Multicenter Prospective Clinical Trial. CROHNS & COLITIS 360 2020; 2:otaa073. [PMID: 34192247 PMCID: PMC7797742 DOI: 10.1093/crocol/otaa073] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Indexed: 12/20/2022]
Abstract
Background Granulocyte and monocyte adsorptive apheresis (GMA) has been used for therapy of steroid-dependent/refractory ulcerative colitis (UC). The aim of this study was to investigate the effectiveness of GMA in UC patients not receiving steroids. Methods We conducted a single-arm, open-label, and multicenter prospective clinical trial. UC patients who had insufficient responses to 5-aminosalicylic acid received GMA twice a week for 5 weeks. Results The response rate of all patients was 58.2% (39/67). Of the 39 patients who achieved a response, 74.4% achieved endoscopically confirmed mucosal healing. Conclusions GMA shows effectiveness in inducing remission in UC patients not receiving steroid. EXPECT study demonstrates that granulocyte and monocyte adsorptive apheresis has promising effectiveness with regard to inducing remission in patients with active ulcerative colitis (UC) who are not receiving steroid treatment. The first episode of UC was an independent predictor of a response in multiple logistic regression.
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Affiliation(s)
- Kazuki Kakimoto
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Minoru Matsuura
- Department of Gastroenterology and Hepatology, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Takumi Fukuchi
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Osaka, Japan
| | - Hitoshi Hongo
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Tsuguhiro Kimura
- Department of Gastroenterology, Fujita Gastroenterological Hospital, Takatsuki, Osaka, Japan
| | - Nobuo Aoyama
- Department of Gastroenterology, Gastrointestinal Endoscopy and IBD Center, Aoyama Medical Clinic, Kobe, Hyogo, Japan
| | - Yorihide Okuda
- Department of Gastroenterology, Otemae Hospital, Osaka, Osaka, Japan
| | - Kazuki Aomatsu
- Department of Gastroenterology, Izumiotsu Municipal Hospital, Izumiotsu, Osaka, Japan
| | - Noriko Kamata
- Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan
| | - Yoko Yokoyama
- Department of Intestinal Inflammation Research, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan
| | - Chiemi Mizuno
- Department of Gastroenterology and Hepatology, Saiseikai Suita Hospital, Suita, Osaka, Japan
| | - Takuya Inoue
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Takako Miyazaki
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Shiro Nakamura
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Kazuhide Higuchi
- 2nd Department of Internal Medicine, Osaka Medical College, Takatsuki, Osaka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan
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14
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Kanekura T, Kawahara K. Adsorptive granulocyte and monocyte apheresis: A potentially relevant therapeutic option for COVID-19. Int J Infect Dis 2020; 99:1-2. [PMID: 32721534 PMCID: PMC7834290 DOI: 10.1016/j.ijid.2020.07.025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/15/2020] [Accepted: 07/21/2020] [Indexed: 11/03/2022] Open
Abstract
The overproduction of proinflammatory cytokines and subsequent thromboembolism are major problems of coronavirus disease 2019 (COVID-19). Adsorptive granulocyte and monocyte apheresis (GMA), used for ulcerative colitis, is an extracorporeal therapy designed to remove activated myeloid lineage cells. Previous studies have demonstrated that GMA decreases proinflammatory cytokines and neutrophil-platelet aggregates. The effect of GMA on COVID-19 in a patient with ulcerative colitis was recently reported. The modes of action of GMA together with the findings of this case report indicate that GMA could be a relevant treatment option for COVID-19.
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Affiliation(s)
- Takuro Kanekura
- Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
| | - Koichi Kawahara
- Laboratory of Functional Foods, Department of Biomedical Engineering, Osaka Institute of Technology, 5-16-1 Omiya, Asahi-ku, Osaka 535-8585, Japan
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15
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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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16
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Tanida S, Ozeki K, Mizoshita T, Kitagawa M, Ozeki T, Tanaka M, Nishie H, Shimura T, Kubota E, Kataoka H. Combination Therapy With Tofacitinib Plus Intensive Granulocyte and Monocyte Adsorptive Apheresis as Induction Therapy for Refractory Ulcerative Colitis. J Clin Med Res 2020; 12:36-40. [PMID: 32010420 PMCID: PMC6968921 DOI: 10.14740/jocmr4037] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 12/09/2019] [Indexed: 12/30/2022] Open
Abstract
Background The use of monotherapy with intensive granulocyte and monocyte adsorptive apheresis (GMA) or a Janus kinase (JAK) inhibitor has been limited to patients with refractory ulcerative colitis (UC). The efficacy and safety of combination therapy with tofacitinib (TOF) plus intensive GMA (two sessions per week) for refractory UC have not been evaluated. Methods This retrospective study evaluated the 10-week efficacy of combination therapy with TOF plus intensive GMA in patients with refractory UC. Results Of seven patients who received a combination therapy with TOF plus intensive GMA, 71.4% achieved clinical remission at 10 weeks. The percentages of patients with mucosal healing and complete mucosal healing at 10 weeks were 100% and 42.9%, respectively. The mean full Mayo score and endoscopic subscore at baseline were 8.71 ± 0.80 and 2.4 ± 0.2, respectively, and the corresponding values at 10 weeks were 1.57 ± 0.48 and 0.6 ± 0.2 (P < 0.01), respectively. Adverse events of an orolabial herpes and temporary increase in creatinine phosphokinase (CK) and triglyceride were observed in three patients. Conclusions Based on these outcomes, combination therapy with TOF plus intensive GMA was well tolerated and may be useful for induction of clinical remission in patients with refractory UC.
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Affiliation(s)
- Satoshi Tanida
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Keiji Ozeki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Tsutomu Mizoshita
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Mika Kitagawa
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Takanori Ozeki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Mamoru Tanaka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Hirotada Nishie
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Takaya Shimura
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Eiji Kubota
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
| | - Hiromi Kataoka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City, Aichi Prefecture, Japan
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17
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Fukuchi T, Koga H, Kaichi S, Ishikawa A, Horita T, Araki R, Yokota A, Namba Y, Kyo M, Eguchi T, Shimazu K. Single-Needle Intensive Granulocyte and Monocyte Adsorptive Apheresis Is Suitable for Elderly Patients With Active Ulcerative Colitis Taking no Corticosteroids or Biologics. Ther Apher Dial 2019; 23:224-232. [PMID: 31025824 DOI: 10.1111/1744-9987.12819] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 01/25/2019] [Indexed: 12/29/2022]
Abstract
Twice-weekly intensive granulocyte/monocyte adsorptive apheresis is effective and safe for ulcerative colitis, but maintaining two blood access routes is problematic. We previously reported that intensive granulocyte/monocyte adsorptive apheresis using a single needle in ulcerative colitis is effective and safe. We hypothesized that the efficacy and safety of single-needle intensive granulocyte/monocyte adsorptive apheresis for ulcerative colitis would especially benefit the elderly. We enrolled 17 elderly ulcerative colitis patients to receive single-needle intensive granulocyte/monocyte adsorptive apheresis, 27 elderly ulcerative colitis patients to receive double-needle intensive granulocyte/monocyte adsorptive apheresis, and 52 nonelderly ulcerative colitis patients to receive single-needle intensive granulocyte/monocyte adsorptive apheresis. Remission and mucosal healing rates after treatment did not differ significantly between elderly ulcerative colitis patients receiving single-needle apheresis and the other two groups. In addition, no serious adverse effects, including blood clots, were observed in single-needle intensive granulocyte/monocyte adsorptive apheresis patients. Single-needle intensive granulocyte/monocyte adsorptive apheresis might be a novel alternative therapeutic option for elderly ulcerative colitis patients before considering corticosteroids.
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Affiliation(s)
- Takumi Fukuchi
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Japan
| | - Hideaki Koga
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Japan
| | - Shinji Kaichi
- Department of Gastroenterology and Hepatology, Iseikai Hospital, Osaka, Japan
| | - Akira Ishikawa
- Department of Gastroenterological Surgery, Iseikai Hospital, Osaka, Japan
| | - Takahisa Horita
- Dialysis Center, Iseikai Fuzoku Iseikai Clinic, Osaka, Japan
| | - Ryota Araki
- Dialysis Center, Juso Iseikai Clinic, Osaka, Japan
| | - Atsushi Yokota
- Dialysis Center, Shin-Osaka Iseikai Clinic, Osaka, Japan
| | | | - Masahiro Kyo
- Dialysis Center, Osaka Umeda Iseikai Dialysis Clinic, Osaka, Japan
| | - Takaaki Eguchi
- Department of Gastroenterology and Hepatology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
| | - Keiji Shimazu
- Department of Nephrology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan
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18
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Yanagisawa K, Murakami M, Kondo Y, Oguma S, Kobayashi S, Miyasaka H, Shinohara T, Tomori A, Nakano Y, Furuhata S, Ikezoe M. Efficacy and Safety of Adsorptive Granulocyte and Monocyte Apheresis in Elderly and Pregnant Patients With Ulcerative Colitis. Ther Apher Dial 2019; 23:217-223. [PMID: 31025815 PMCID: PMC6852531 DOI: 10.1111/1744-9987.12818] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 01/18/2019] [Indexed: 02/06/2023]
Abstract
In patients with active ulcerative colitis (UC), adsorptive granulocyte/monocyte apheresis (GMA) is expected to promote remission. We conducted a retrospective cohort study to evaluate the efficacy and safety of GMA in patients with active UC. Twenty-one UC patients including five pregnant or lactating mothers and four elderly patients (aged >60 years) received up to 10 GMA sessions. UC severity was evaluated at baseline and after GMA therapy according to Lichtiger's Clinical Activity Index (CAI). We defined clinical remission as CAI ≤4. Overall, the median CAI score after GMA therapy had decreased from 9 to 4 (P < 0.001). The clinical remission rate was 62%, but in the elderly and pregnant or lactating mothers, the remission rates were 100% and 60%, respectively. No severe adverse effects were seen in this study. Our results may support GMA as an effective and safe treatment for active UC patients, including elderly patients and pregnant cases.
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Affiliation(s)
- Kazuki Yanagisawa
- Department of Clinical EngineeringSaku Central Hospital Advanced Care CenterNaganoJapan
| | - Minoru Murakami
- Department of NephrologySaku Central Hospital Advanced Care CenterNaganoJapan
| | - Yuya Kondo
- Department of Clinical EngineeringSaku Central Hospital Advanced Care CenterNaganoJapan
| | - Shun Oguma
- Department of Clinical EngineeringSaku Central Hospital Advanced Care CenterNaganoJapan
| | - Shun Kobayashi
- Department of Clinical EngineeringSaku Central Hospital Advanced Care CenterNaganoJapan
| | - Hiroshi Miyasaka
- Department of Clinical EngineeringSaku Central Hospital Advanced Care CenterNaganoJapan
| | - Tomoaki Shinohara
- Department of GastroenterologySaku Central Hospital Advanced Care CenterNaganoJapan
| | - Akihisa Tomori
- Department of GastroenterologySaku Central Hospital Advanced Care CenterNaganoJapan
| | - Yui Nakano
- Department of NephrologySaku Central Hospital Advanced Care CenterNaganoJapan
| | - Shunichi Furuhata
- Department of NephrologySaku Central Hospital Advanced Care CenterNaganoJapan
| | - Masaya Ikezoe
- Department of NephrologySaku Central Hospital Advanced Care CenterNaganoJapan
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19
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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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20
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Yamamoto T. Clinical Characteristics of Japanese Patients with Palmoplantar Pustulosis. Clin Drug Investig 2019; 39:241-252. [DOI: 10.1007/s40261-018-00745-6] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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21
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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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22
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Kanekura T. Clinical and immunological effects of adsorptive myeloid lineage leukocyte apheresis in patients with immune disorders. J Dermatol 2018; 45:943-950. [PMID: 29782055 DOI: 10.1111/1346-8138.14471] [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: 03/13/2018] [Accepted: 04/13/2018] [Indexed: 01/18/2023]
Abstract
Adsorptive granulocyte and monocyte apheresis (GMA) with the Adacolumn® is an extracorporeal treatment, which uses cellulose acetate (CA) beads as adsorptive leukocytapheresis carriers designed to remove elevated and potentially activated myeloid lineage leukocytes. Reports on the clinical efficacy of GMA in patients with skin lesions have appeared in the published work. Dermatological diseases, which are known to respond to GMA, include pyoderma gangrenosum, skin lesions of Behçet's disease, rheumatoid arthritis, pustular psoriasis, psoriatic arthritis, adult-onset Still's disease, Sweet's syndrome, cutaneous allergic vasculitis and systemic lupus erythematosus rashes. In association with clinical studies, efforts to understand the mechanisms of GMA have made significant progress. GMA selectively depletes elevated myeloid lineage leukocytes through binding between blood immunoglobulin G or complement iC3b, which form on the surface of CA beads and the Fcγ receptors or complement receptors expressed on the myeloid lineage cells. However, GMA has immunomodulatory effects including down-modulation of inflammatory cytokine profile, changes in leukocyte surface receptors and induction of regulatory T cells. These actions render GMA a unique non-pharmacological treatment option for patients with chronic dermatoid conditions, which are difficult to treat with pharmacological preparations.
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Affiliation(s)
- Takuro Kanekura
- Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
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23
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Cytapheresis (CAP) with leukocyte removal filter/bead column as one therapeutic option for inflammatory bowel disease. Transfus Apher Sci 2017; 56:689-697. [PMID: 28986009 DOI: 10.1016/j.transci.2017.08.016] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Inflammatory bowel disease (IBD) like Crohn's disease and ulcerative colitis are chronic inflammatory disorders that affect the bowel. The disease is characterized by periods of clinical remission and relapse due to severe intestinal inflammation. Drug therapy of IBD is associated with unpleasant side effects. Further, efficacies of conventional drugs decrease with chronic use and this can represent a major difficulty in the long term management of IBD. However, in active IBD, leukocytes are elevated in the lesion they may be able to be a factor of IBD aggravation. Membrane filters column and leukocyte adsorbing beads have been developed which are direct blood perfusion systems for removing any desired level of leukocytes. Clinical studies with these two new models have shown good effects for active IBD. Clinical data suggest that leukocytapheresis might be an effective adjunct to therapy of IBD, to promote remission, taper conventional drug dosage and potentially should reduce the number of patients who require colectomy. The results may further understandings of the pathophysiology of IBD and this in turn should contribute to a more effective treatment of this disorder.
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Immunological Mechanisms of Adsorptive Cytapheresis in Inflammatory Bowel Disease. Dig Dis Sci 2017; 62:1417-1425. [PMID: 28432476 DOI: 10.1007/s10620-017-4577-z] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Accepted: 04/08/2017] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). The study of immunological pathways involved in the onset of IBD is of fundamental importance to identify potential biological markers of disease activity and specific targets for therapy. Removing excess and activated circulating leukocytes with adsorptive cytapheresis has been shown to be a potentially effective treatment for patients with an inflamed bowel. Adsorptive cytapheresis is a non-pharmacological approach for active IBD, in which known sources of inflammatory cytokines such as activated myeloid lineage leucocytes are selectively depleted from the circulatory system. The decrease in inflammatory load caused by removing these cells is thought to enhance drug therapy and thereby promote disease remission. The benefit of cytapheresis appears to rest upon its ability to reduce levels of certain immune cell populations; however, whether this depletion results in further changes in lymphocyte populations and cytokine production needs further clarification. In this review, we aim to summarize existing evidence on the role of cytapheresis in patients with IBD, its effect on cytokine levels and cellular populations, and to discuss its potential impact on disease activity.
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Ma S, Xu Q, Deng B, Zheng Y, Tian H, Wang L, Ding F. Granulocyte and monocyte adsorptive apheresis ameliorates sepsis in rats. Intensive Care Med Exp 2017; 5:18. [PMID: 28342161 PMCID: PMC5366986 DOI: 10.1186/s40635-017-0129-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 03/08/2017] [Indexed: 01/07/2023] Open
Abstract
Background Overwhelming activation of granulocytes and monocytes is central to inflammatory responses during sepsis. Granulocyte and monocyte adsorptive apheresis (GMA) is an extracorporeal leukocyte apheresis device filled with cellulose acetate beads and selectively adsorbs granulocytes and monocytes from the peripheral blood. Methods In this study, septic rats received the GMA treatment for 2 h at 18 h after cecal ligation and puncture. Results GMA selectively adsorbed activated neutrophils and monocytes from the peripheral blood, reduced serum inflammatory cytokine expression, and seemed to improve organ injuries and animal survival. GMA potentially reduced lung injury by alleviating the infiltration of inflammatory cells and the secretion of cytokines. Conclusions This study showed that selective granulocyte and monocyte adsorption with cellulose acetate beads might ameliorate cecal ligation and puncture (CLP)-induced sepsis and improve survival and organ function.
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Affiliation(s)
- Shuai Ma
- Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Qingqing Xu
- Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Bo Deng
- Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Yin Zheng
- Division of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai, 200040, China
| | - Hongyan Tian
- Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China
| | - Li Wang
- Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China.
| | - Feng Ding
- Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China.
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Morabito V, Novelli S, Poli L, Ferretti G, Ruberto F, Pugliese F, Pretagostini R, Berloco PB, Rossi M. Adacolumn Granulocyte-Apheresis for Alcoholic Hepatitis: Preliminary Study. Transplant Proc 2017; 48:352-8. [PMID: 27109954 DOI: 10.1016/j.transproceed.2015.12.055] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2015] [Accepted: 12/30/2015] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Alcoholic hepatitis (AH) is an acute-on-chronic inflammatory response affecting the liver. It has been recognized that white blood cells (WBCs) are involved in the pathogenesis and in the prognosis of AH. The aim of study was to use Adacolumn, which can selectively adsorb myeloid linage leucocytes (granulocytes and monocytes/macrophages) from the blood in the column and improve the clinical status of patients. MATERIALS Six patients with a diagnosis of AH were treated with Adacolumn granulocyte-apheresis therapy. INCLUSION CRITERIA patients not responders to corticosteroids therapy with Maddrey Discriminant Function (MDF) >32 and MELD score 20-26. The patients underwent five 1-hour sessions for 5 consecutive days with a follow-up at 28 days. The column was placed in an extracorporeal setting with a perfusion rate of 30 mL/min and a duration of 60 minutes. Liver parameters, WBC count, proinflammatory cytokines, coagulation, and predictive scores were valued before and after the cycle of apheresis treatment. RESULTS After 5 days, the findings showed a significant improvement of WBC count (P < .014) and cytokines such as interleukin (IL)-6 (P < .019), tumor necrosis factor α (TNFα) (P < .02), and IL-8 (P < .029). The results probably determined a reduction of aspartate transaminase (AST; P < .02) and alanine transaminase (ALT; P < .011), although we did not observe a significant improve in bilirubin, prothrombin time (PT), and Maddrey score. The improvement of MELD score, depending on an improvement of international normalized ratio for administration of plasma, was not considered. At day 28 of follow-up, PT, IL-6, TNFα, AST and ALT results significantly improved. CONCLUSIONS The Adacolumn apheresis was safe and was able to determine an improvement of clinical status of patients with reduction of inflammatory markers. More patients are needed to validate these results.
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Affiliation(s)
- V Morabito
- Italian National Transplant Center, Rome, Italy.
| | - S Novelli
- Department of Aerospace and Mechanical Engineering, Sapienza University of Rome, Rome, Italy
| | - L Poli
- Italian National Transplant Center, Rome, Italy
| | - G Ferretti
- Department of Infectious Disease, Sapienza University of Rome, Rome, Italy
| | - F Ruberto
- Department of Anesthesia and Intensive Care, Sapienza University of Rome, Rome, Italy
| | - F Pugliese
- Department of Anesthesia and Intensive Care, Sapienza University of Rome, Rome, Italy
| | | | - P B Berloco
- Italian National Transplant Center, Rome, Italy
| | - M Rossi
- Italian National Transplant Center, Rome, Italy
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Nishise S, Abe Y, Nomura E, Sato T, Sasaki Y, Iwano D, Yoshizawa K, Yagi M, Nishise Y, Ueno Y. Relationship Between Tumor Necrosis Factor-α Release and Granulocyte and Monocyte Adsorption to Cellulose Acetate Beads. Ther Apher Dial 2014; 18:252-7. [DOI: 10.1111/1744-9987.12212] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Shoichi Nishise
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yasuhiko Abe
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Eiki Nomura
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Takeshi Sato
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yu Sasaki
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Daisuke Iwano
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Kazuya Yoshizawa
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Makoto Yagi
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yuko Nishise
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology; Yamagata University Faculty of Medicine; Yamagata Japan
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Fujisawa T, Tawada C, Mizutani Y, Doi T, Yoshida S, Ogura S, Seishima M. Efficacy of Granulocyte and Monocyte Adsorption Apheresis for Treatment of Palmoplantar Pustulosis. Ther Apher Dial 2014; 18:238-43. [DOI: 10.1111/1744-9987.12210] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Affiliation(s)
- Tomomi Fujisawa
- Department of Dermatology; Gifu University Graduate School of Medicine; Gifu Japan
| | - Chisato Tawada
- Department of Dermatology; Gifu University Graduate School of Medicine; Gifu Japan
| | - Yoko Mizutani
- Department of Dermatology; Gifu University Graduate School of Medicine; Gifu Japan
| | - Tomoaki Doi
- Department of Emergency and Disaster Medicine; Gifu University Graduate School of Medicine; Gifu Japan
| | - Shozo Yoshida
- Department of Emergency and Disaster Medicine; Gifu University Graduate School of Medicine; Gifu Japan
| | - Shinji Ogura
- Department of Emergency and Disaster Medicine; Gifu University Graduate School of Medicine; Gifu Japan
| | - Mariko Seishima
- Department of Dermatology; Gifu University Graduate School of Medicine; Gifu Japan
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Fukuchi T, Nakase H, Matsuura M, Yoshino T, Toyonaga T, Ohmori K, Ubukata S, Ueda A, Eguchi T, Yamashita H, Ito D, Ashida K. Effect of intensive granulocyte and monocyte adsorptive apheresis in patients with ulcerative colitis positive for cytomegalovirus. J Crohns Colitis 2013; 7:803-11. [PMID: 23352104 DOI: 10.1016/j.crohns.2012.12.003] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Revised: 11/17/2012] [Accepted: 12/06/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Cytomegalovirus (CMV) exacerbates ulcerative colitis (UC) refractory to immunosuppressive therapies. The conditions under which CMV reactivation occurs in patients with UC, however, is unclear. In addition, the diagnostic and treatment strategies for UC positive for CMV have not been established. Granulocyte and monocyte adsorptive apheresis (GMAA) is natural biological therapy for UC in which the granulocytes/macrophages producing inflammatory cytokines are removed. We investigated the rate of colonic CMV reactivation and the efficacy of GMAA in active UC patients positive for CMV without concomitant corticosteroid (CS) therapy. METHODS Fifty-one active UC patients without concomitant CS therapy were enrolled. Colonic CMV reactivation was examined by real-time polymerase chain reaction (PCR) using biopsy specimen and/or histological examination. All patients were treated with intensive GMAA (twice per week). Rates of clinical remission and mucosal healing were compared between UC patients positive and negative for CMV. RESULTS Of 51 patients, 15 (29.4%) were diagnosed as CMV positive. The clinical remission rates following intensive GMAA did not differ between UC patients positive and negative for CMV (73.3% vs 69.4%, p=0.781). Proportion of patients achieving mucosal healing was also similar between these two groups. CMV-DNA became negative in all UC patients positive for CMV who achieved clinical remission 1 week after completion of intensive GMAA. CONCLUSIONS Intestinal inflammation might trigger CMV reactivation in a subpopulation of active UC patients without CS treatment. GMAA could be a promising option for active UC positive for CMV.
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Affiliation(s)
- Takumi Fukuchi
- Department of Gastroenterology and Hepatology, Osakafu Saiseikai Nakatsu Hospital, Osaka, Japan.
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Sakanoue M, Takeda K, Kawai K, Kanekura T. Granulocyte and Monocyte Adsorption Apheresis for Refractory Skin Diseases due to Activated Neutrophils, Psoriasis, and Associated Arthropathy. Ther Apher Dial 2013; 17:477-83. [DOI: 10.1111/1744-9987.12113] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Masanao Sakanoue
- Department of Dermatology; Kagoshima University Graduate School of Medical and Dental Sciences; Kagoshima
- Japan Immunoresearch Laboratories; Takasaki Japan
| | - Koichiro Takeda
- Department of Dermatology; Kagoshima University Graduate School of Medical and Dental Sciences; Kagoshima
- Japan Immunoresearch Laboratories; Takasaki Japan
| | - Kazuhiro Kawai
- Department of Dermatology; Kagoshima University Graduate School of Medical and Dental Sciences; Kagoshima
- Japan Immunoresearch Laboratories; Takasaki Japan
| | - Takuro Kanekura
- Department of Dermatology; Kagoshima University Graduate School of Medical and Dental Sciences; Kagoshima
- Japan Immunoresearch Laboratories; Takasaki Japan
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Bamba T, Yamamoto T, Umegae S, Matsumoto K. Effects of preoperative leukocytapheresis on inflammatory cytokines following surgery for ulcerative colitis: a prospective randomized study. J Clin Apher 2013; 29:107-12. [PMID: 24000140 DOI: 10.1002/jca.21299] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2013] [Revised: 07/22/2013] [Accepted: 08/08/2013] [Indexed: 12/17/2022]
Abstract
Targeted extracorporeal granulocyte and monocyte apheresis (GMA) has produced clinical efficacy together with down modulation of specific inflammatory cytokines in patients with ulcerative colitis (UC). This study was to investigate if preoperative GMA produces immunological effect on dysregulated immune activity after restorative proctocolectomy (RPC) in patients with UC. Forty patients requiring RPC were included. Twenty randomly selected patients received five GMA sessions with the Adacolumn over two consecutive weeks before RPC (GMA group). RPC was performed within 2 weeks following the last GMA session. The other 20 patients did not receive GMA before RPC (non-GMA group). Blood samples were obtained immediately before surgery, at 1 h after surgery, and on postoperative Days 1, 3, and 7 from all patients. Abdominal exudate was obtained from the drainage tube at 1 h after surgery, and on postoperative Days 1, 3, and 7. Concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in plasma and peritoneal fluid from a drainage tube were measured by enzyme linked immunosorbent assay. Between the two groups, patients were matched with respect to age, sex, UC duration, severity, extent and the dose of prednisolone at surgery. IL-1β, IL-6, and TNF-α levels in plasma and peritoneal fluid were not significantly different between the two groups during the entire study period. Based on the assays of IL-1β, IL-6, and TNF-α levels in the plasma and the peritoneal fluid, this study did not find any effect on these inflammatory cytokines by preoperative GMA in patients with UC who underwent RPC.
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Affiliation(s)
- Takuya Bamba
- Department of Surgery, Inflammatory Bowel Disease Center, Yokkaichi Social Insurance Hospital, Yokkaichi, Mie, Japan
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Tanaka T, Sugiyama S, Goishi H, Kajihara T, Akagi M, Miura T. Treatment of children and adolescents with ulcerative colitis by adsorptive depletion of myeloid lineage leucocytes as monotherapy or in combination with low dose prednisolone after failure of first-line medications. BMC Gastroenterol 2013; 13:130. [PMID: 23961883 PMCID: PMC3765231 DOI: 10.1186/1471-230x-13-130] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2013] [Accepted: 08/10/2013] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Currently available drugs for the treatment of ulcerative colitis (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour necrosis factor (TNF)-α biologics. Among these medications, corticosteroids in children and adolescents may adversely affect the patients' growth and development. Further, UC patients have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocytes, which release TNF-α as a significant exacerbating factor. Accordingly, depletion of these cells by granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote UC remission. The objective of this study was to evaluate the efficacy of GMA in children and adolescents in whom conventional first-line medications had failed to induce remission. METHODS In a single centre setting, between 2007 and 2012, a total of 24 consecutive children and adolescents, age 11-19 years were given mesalazine or sulphasalazine as a first-line medication. Seventeen patients relapsed or did not respond to the first-line medications, and received GMA with the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) were to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. RESULTS Seven patients achieved remission with the first-line medications and did not receive GMA. Five patients did not respond to the first 5 GMA sessions and received PSL plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions. At entry, the average CAI was 12.7 ± 2.5, range 8-17, and the average endoscopic index was 8.5 ± 1.5, range 7-11. The corresponding values at week 12 were 2.1 ± 0.2, range 1-4 (P < 0.001) and 2.4 ± 0.2, range 1-4 (P < 0.001). PSL was tapered to 0 mg within 3 months. CONCLUSIONS With the strategy we applied in this study, all 24 consecutive patients achieved remission. In growing patients with active UC refractory to first-line medications, GMA was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering of the PSL dose soon after remission was not associated with UC relapse. Therefore, the majority of young corticosteroid naive UC patients in whom first-line salicylates have failed may respond to GMA and be spared from additional drug therapy. Avoiding corticosteroids at an early stage of UC should ensure better long-term clinical course.
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Affiliation(s)
- Tomotaka Tanaka
- Department of Gastroenterology, Akitsu Prefectural Hospital, 4388 Akitsu cho, Hiroshima 739-2402, Japan.
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Tanaka T, Sugiyama S, Goishi H, Kajihara T, Akagi M, Miura T. Treatment of children and adolescents with ulcerative colitis by adsorptive depletion of myeloid lineage leucocytes as monotherapy or in combination with low dose prednisolone after failure of first-line medications. BMC Gastroenterol 2013. [PMID: 23961883 DOI: 10.1016/s1873-9946(13)60351-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Currently available drugs for the treatment of ulcerative colitis (UC) include salicylates, thiopurines, corticosteroids and new anti-tumour necrosis factor (TNF)-α biologics. Among these medications, corticosteroids in children and adolescents may adversely affect the patients' growth and development. Further, UC patients have elevated and activated myeloid lineage leucocytes including the CD14 + CD16+ monocytes, which release TNF-α as a significant exacerbating factor. Accordingly, depletion of these cells by granulocyte/monocyte adsorption (GMA) should alleviate inflammation and promote UC remission. The objective of this study was to evaluate the efficacy of GMA in children and adolescents in whom conventional first-line medications had failed to induce remission. METHODS In a single centre setting, between 2007 and 2012, a total of 24 consecutive children and adolescents, age 11-19 years were given mesalazine or sulphasalazine as a first-line medication. Seventeen patients relapsed or did not respond to the first-line medications, and received GMA with the Adacolumn, 2 sessions in the first week, and then weekly, up to 11 sessions. Patients who achieved a decrease of ≥5 in the clinical activity index (CAI) were to continue with GMA, while non-responders were to receive 0.5 to 1.0 mg/kg/day prednisolone (PSL) plus additional GMA sessions similar to GMA responder cases. At entry and week 12, patients were clinically and endoscopically evaluated, allowing each patient to serve as her/his own control. RESULTS Seven patients achieved remission with the first-line medications and did not receive GMA. Five patients did not respond to the first 5 GMA sessions and received PSL plus GMA, while 12 patients responded to the first 5 GMA sessions and received additional sessions. At entry, the average CAI was 12.7 ± 2.5, range 8-17, and the average endoscopic index was 8.5 ± 1.5, range 7-11. The corresponding values at week 12 were 2.1 ± 0.2, range 1-4 (P < 0.001) and 2.4 ± 0.2, range 1-4 (P < 0.001). PSL was tapered to 0 mg within 3 months. CONCLUSIONS With the strategy we applied in this study, all 24 consecutive patients achieved remission. In growing patients with active UC refractory to first-line medications, GMA was associated with clinical remission and mucosal healing, while in non-responders to GMA monotherapy, addition of a low dose PSL enhanced the efficacy of GMA and tapering of the PSL dose soon after remission was not associated with UC relapse. Therefore, the majority of young corticosteroid naive UC patients in whom first-line salicylates have failed may respond to GMA and be spared from additional drug therapy. Avoiding corticosteroids at an early stage of UC should ensure better long-term clinical course.
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Affiliation(s)
- Tomotaka Tanaka
- Department of Gastroenterology, Akitsu Prefectural Hospital, 4388 Akitsu cho, Hiroshima 739-2402, Japan.
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Ramlow W, Waitz G, Sparmann G, Prophet H, Bodammer P, Emmrich J. First Human Application of a Novel Adsorptive-Type Cytapheresis Module in Patients With Active Ulcerative Colitis: A Pilot Study. Ther Apher Dial 2013; 17:339-47. [DOI: 10.1111/1744-9987.12007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
| | | | | | | | - Peggy Bodammer
- Division of Gastroenterology; University of Rostock; Rostock; Germany
| | - Jörg Emmrich
- Division of Gastroenterology; University of Rostock; Rostock; Germany
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Nakano R, Iwakiri R, Ikeda Y, Kishi T, Tsuruoka N, Shimoda R, Sakata Y, Yamaguchi K, Fujimoto K. Factors affecting short- and long-term effects of leukocyte removal therapy in active ulcerative colitis. J Gastroenterol Hepatol 2013; 28:303-8. [PMID: 23339387 DOI: 10.1111/jgh.12049] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/16/2012] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND AIM Leukocyte removal therapy (LRT) is recognized as an effective treatment for active ulcerative colitis (UC). In this study, factors associated with the efficacy and long-term effects of LRT were evaluated. METHODS From April 1998 to March 2010, 98 patients with moderate to severe UC were randomly assigned to granulocyte and monocyte/macrophage adsorptive apheresis (GMA) (n = 47) or leukocytapheresis (LCAP) (n = 51) treatment. Patients received two sessions of LRT in the first week, followed by three weekly administrations. All patients were treated with 5-aminosalicylic acid and corticosteroid. Steroid doses were tapered if patients achieved clinical improvement. Clinical remission was defined as a decrease in clinical activity index to < 4 and endoscopic findings to Matts' grade 1 or 2. When clinical activity index decreased but still remained ≥ 5 and Matts' grading was 1 or 2, the patient was considered to have improved. Patients were observed for at least 1 year and diagnosed as relapsed when additional treatment was required. RESULTS Seventy-one (73%) patients achieved clinical remission or improvement. No significant difference was found between LCAP and GMA. Increased age, ≥ 3 attacks of UC, and ≥ 2 sessions of LRT were indicative of refractoriness to LRT. During 1 year observation, 28 patients were relapsed. Duration of UC, ≥ 3 attacks of UC, and ≥ 2 sessions of LRT were indicative of refractoriness to the long-term effects of LRT. CONCLUSION Both GMA and LCAP were effective to treat active UC. However, long duration of UC, multiple UC attacks, and past history of LRT reduce the efficacy.
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Affiliation(s)
- Ryo Nakano
- Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, Saga, Japan
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Hanai H, Iida T, Ikeya K, Abe J, Maruyama Y, Shimura T, Sugimoto K, Watanabe F. A new paradigm in ulcerative colitis: regulatory T cells are key factor which induces/exacerbates UC through an immune imbalance. Mol Immunol 2012; 54:173-80. [PMID: 23280396 DOI: 10.1016/j.molimm.2012.11.015] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Revised: 11/22/2012] [Accepted: 11/27/2012] [Indexed: 02/07/2023]
Abstract
Leukocytapheresis (LCAP) appears to remove or inactivate inflammatory cells and to reset immunological responses, resulting to cure responders of ulcerative colitis (UC). The changes of T cell subsets were investigated in UC patients treated with LCAP. Levels of T cell subsets in peripheral blood before and after LCAP were analysed by flow cytometric analysis. Of 20 UC patients, 13 (65%) achieved remission and 2 (10%) showed the improvement of UC symptoms. Ratios of some T cell subtypes such as regulatory T (Treg) cells and memory T cells to CD4(+) T cells changed significantly only in responders. Especially, ratio of resting Treg/CD4(+) T cells was significantly increased after the first LCAP session, and then one of activated Treg/CD4(+) T cells was increased after 2 week. This may lead to the development of a new UC paradigm in which an imbalance in Treg cell subsets triggers the onset and/or exacerbation of UC.
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Affiliation(s)
- Hiroyuki Hanai
- Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, Hamamatsu, Japan.
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Suzuki A, Haruna K, Mizuno Y, Kuwae Y, Ono Y, Okumura K, Negi O, Kon Y, Takeuchi K, Takamori K, Ikeda S, Suga Y. Successful Treatment of Three Cases of Generalized Pustular Psoriasis With Granulocyte and Monocyte Adsorption Apheresis. Ther Apher Dial 2012; 16:445-8. [DOI: 10.1111/j.1744-9987.2012.01109.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
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C Leitner G, Worel N, Vogelsang H. Selective Granulocyte and Monocyte Apheresis as a Non-Pharmacological Option for Patients with Inflammatory Bowel Disease. ACTA ACUST UNITED AC 2012; 39:246-252. [PMID: 22969694 DOI: 10.1159/000341801] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2012] [Accepted: 07/11/2012] [Indexed: 12/18/2022]
Abstract
Ulcerative colitis and Crohn's disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient's blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn( (®) ) (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba( (®) ) FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment.
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Affiliation(s)
- Gerda C Leitner
- University Clinic for Blood Group Serology and Transfusion Medicine, Vienna, Austria
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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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Sono K, Yamada A, Yoshimatsu Y, Takada N, Suzuki Y. Factors associated with the loss of response to infliximab in patients with Crohn's disease. Cytokine 2012; 59:410-6. [PMID: 22633084 DOI: 10.1016/j.cyto.2012.04.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2012] [Revised: 04/02/2012] [Accepted: 04/18/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIMS The efficacy of infliximab (IFX) has validated the role of TNF-α in the immunopathogenesis of Crohn's disease (CD). However, antibodies to IFX emerge, which impair its efficacy. This study investigated factor(s) associated with the loss of response (LOR) to IFX and how IFX non-responders may be treated. METHODS Seventy-four patients, 36 IFX responders (GI) and 38 with LOR (GII) were included. Trough IFX level, CD activity index (CDAI) and immunological markers during IFX maintenance therapy were measured. Adsorptive granulocyte/monocyte apheresis (GMA) was applied to patients with LOR. RESULTS The durations of CD, 9.3 ± 5.5 yr and IFX therapy, 3.4 ± 2.0 yr in GII were longer vs GI (P=0.02, P=0.01). Similarly, C-reactive protein (P<0.0001) and CDAI (P<0.0001) in GII were higher. The median trough IFX was 4.7 μg/mL in GI and 8.4 μg/mL in GII, while the dose frequency was 8 weeks in GI and 4 weeks in GII. Soluble interleukin-2 receptor (sIL-2R) was higher in GII vs GI (P<0.001). Seropositive rates of anti-nuclear antibodies (ANA) and circulating immune complexes (CIC) in GII were 50.0% and 68.4%, significantly higher vs GI (P<0.05, P<0.01). Patients with LOR duration <1.5 yr showed higher CDAI and sIL-2R (P<0.05) vs patients with LOR duration <1.5 yr. Fifteen GII patients received GMA plus IFX combination and 46.7% responded. IL-10 increased in GMA-responders (P<0.05), while CIC and ANA decreased (P=0.0237, P=0.0463). CONCLUSIONS Patients with LOR to IFX had dysregulated immune response despite uncompromised trough IFX level. Further, inadequate T-cell differentiation by IFX was suggested. GMA appeared to benefit LOR patients by immunoregulation.
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Affiliation(s)
- Koji Sono
- Internal Medicine, Toho University, Sakura Medical Centre, Chiba, Japan
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Hidaka M, Fukuzawa K. Down-Modulation of Toll-Like Receptor 2 Expression on Granulocytes and Suppression of Interleukin-8 Production Due To In Vitro Treatment With Cellulose Acetate Beads. Ther Apher Dial 2011; 15:572-8. [DOI: 10.1111/j.1744-9987.2011.00992.x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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Naito Y, Takagi T, Yoshikawa T. Neutrophil-dependent oxidative stress in ulcerative colitis. J Clin Biochem Nutr 2011; 41:18-26. [PMID: 18392100 PMCID: PMC2274988 DOI: 10.3164/jcbn.2007003] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2007] [Accepted: 04/11/2007] [Indexed: 01/17/2023] Open
Abstract
Neutrophil accumulation within epithelial crypts and in the intestinal mucosa directly correlates with clinical disease activity and epithelial injury in ulcerative colitis (UC). Current advances have defined the mechanisms by which neutrophils are activated or migrate across mucosal epithelia. A better understanding of this process will likely provide new insights into novel treatment strategies for UC. Especially, activated neutrophils produce reactive oxygen and nitrogen species within intestinal mucosa, which induce oxidative stress. In clinically, we have succeeded to develop a novel granulocytes adsorptive apheresis therapy for UC. In this article, we discuss current advances to define the role of neutrophils-dependent oxidative stress in UC.
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Affiliation(s)
- Yuji Naito
- Medical Proteomics, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Ng SC, Chan FKL, Sung JJY. Review article: the role of non-biological drugs in refractory inflammatory bowel disease. Aliment Pharmacol Ther 2011; 33:417-27. [PMID: 21138457 DOI: 10.1111/j.1365-2036.2010.04541.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Up to one-third of patients with inflammatory bowel disease (IBD) do not respond to, or are intolerant of conventional immunosuppressive drugs. Although biological agents are alternative treatments, they may not be suitable or available to some patients. AIM To review the evidence for use of nonbiological drugs in the treatment of patients with IBD refractory to corticosteroids or thiopurines. METHODS A literature search was performed using PubMed for English language publications with predetermined search criteria to identify relevant studies. RESULTS Published evidence from uncontrolled series and controlled clinical trials has been used to produce a practical approach relevant to clinical practice which incorporates the indication, optimal dose, and side effects of various therapies including tacrolimus, methotrexate, thalidomide, tioguanine, mycophenolate mofotil, leucocyte apheresis, nutritional therapy, antibiotics, probiotics, allopurinol, rectal acetarsol and ciclosporin in the treatment of patients with refractory ulcerative colitis and Crohn's disease. Approaches to optimise thiopurine efficacy are also discussed. CONCLUSIONS Patients with IBD refractory to corticosteroids or thiopurines may respond to alternative anti-inflammatory chemical molecules, but the evidence base for many of these alternatives is limited and further trials are needed.
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Affiliation(s)
- S C Ng
- Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong.
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Thanaraj S, Hamlin PJ, Ford AC. Systematic review: granulocyte/monocyte adsorptive apheresis for ulcerative colitis. Aliment Pharmacol Ther 2010; 32:1297-306. [PMID: 21050231 DOI: 10.1111/j.1365-2036.2010.04490.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with ulcerative colitis (UC) that is chronically active despite 5-aminosalicylates or immunomodulators, or who are dependent on corticosteroids to maintain remission, have limited treatment options. Granulocyte/monocyte adsorptive apheresis (GMAA) may have a role in this situation. AIM To conduct a systematic review of GMAA in UC. METHODS MEDLINE, EMBASE and the Cochrane central register of controlled trials were searched to identify randomized controlled trials (RCTs) comparing GMAA with conventional medical therapy, sham procedure or 'intensive' with 'conventional' GMAA regimens in adult UC patients. Studies reported clinical remission or response rates. RESULTS Ten RCTs were eligible. Formal meta-analysis was not undertaken due to concerns about methodological quality of identified studies. Compared with medical therapy, remission rates with GMAA were generally higher, and corticosteroid-sparing effects were observed. Compared with sham procedure, GMAA did not achieve significantly higher remission rates. 'Intensive' GMAA regimens demonstrated generally higher remission rates, and time to remission was shorter compared with 'conventional' regimens. Only two RCTs were at low risk of bias. Six were conducted in Japanese patients, which may limit generalizability. CONCLUSIONS Granulocyte/monocyte adsorptive apheresis appears of some benefit in UC. High-quality RCTs comparing granulocyte/monocyte adsorptive apheresis with conventional medical therapy or sham procedure in Western populations, with disease activity confirmed endoscopically, are required.
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Affiliation(s)
- S Thanaraj
- Leeds General Infirmary, Leeds Gastroenterology Institute, UK
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Hanai H, Takeda Y, Eberhardson M, Gruber R, Saniabadi AR, Winqvist O, Lofberg R. The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review. Clin Exp Immunol 2010; 163:50-8. [PMID: 21078086 DOI: 10.1111/j.1365-2249.2010.04279.x] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leucocytes which infiltrate the colonic mucosa in vast numbers. Myeloid leucocytes such as the CD14(+) CD16(+) monocytes are major sources of tumour necrosis factor (TNF)-α, and therefore selective granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance efficacy of pharmacological therapy. However, studies in IBD have reported both impressive as well as disappointing efficacy outcomes, indicating that patients' demographic factors might determine responders or non-responders to GMA. Nonetheless, this non-drug intervention has an excellent safety profile, and therapeutic GMA is expected to expand. In this review, attempts have been made to compile an update on the mode of actions (MoA) of the Adacolumn GMA. The MoA of GMA appears to be more than adsorption of excess neutrophils and TNF-producing CD14(+) CD16(+) monocytes per se. Adsorbed GMs release interleukin (IL)-1 receptor antagonist, hepatocyte growth factor and soluble TNF receptors, which are anti-inflammatory. Additionally, a sustained increase in lymphocytes including the regulatory CD4(+) CD25(+) T cells (lymphocyte sparing) is seen post-GMA. The impact of GMA on the immune system is potentially very interesting in the context of treating immune-related diseases. Future studies are expected to add intriguing insights to the MoA of GMA.
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Affiliation(s)
- H Hanai
- Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, 26 Shirowacho, Hamamatsu, Japan.
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Hanai H, Takeda Y, Eberhardson M, Gruber R, Saniabadi AR, Winqvist O, Lofberg R. The mode of actions of the Adacolumn therapeutic leucocytapheresis in patients with inflammatory bowel disease: a concise review. Clin Exp Immunol 2010. [PMID: 21078086 DOI: 10.1111/j.1365-2249.2010.04279] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leucocytes which infiltrate the colonic mucosa in vast numbers. Myeloid leucocytes such as the CD14(+) CD16(+) monocytes are major sources of tumour necrosis factor (TNF)-α, and therefore selective granulocyte/monocyte (GM) adsorption (GMA) should promote remission or enhance efficacy of pharmacological therapy. However, studies in IBD have reported both impressive as well as disappointing efficacy outcomes, indicating that patients' demographic factors might determine responders or non-responders to GMA. Nonetheless, this non-drug intervention has an excellent safety profile, and therapeutic GMA is expected to expand. In this review, attempts have been made to compile an update on the mode of actions (MoA) of the Adacolumn GMA. The MoA of GMA appears to be more than adsorption of excess neutrophils and TNF-producing CD14(+) CD16(+) monocytes per se. Adsorbed GMs release interleukin (IL)-1 receptor antagonist, hepatocyte growth factor and soluble TNF receptors, which are anti-inflammatory. Additionally, a sustained increase in lymphocytes including the regulatory CD4(+) CD25(+) T cells (lymphocyte sparing) is seen post-GMA. The impact of GMA on the immune system is potentially very interesting in the context of treating immune-related diseases. Future studies are expected to add intriguing insights to the MoA of GMA.
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Affiliation(s)
- H Hanai
- Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, 26 Shirowacho, Hamamatsu, Japan.
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Muratov V, Lundahl J, Mandic-Havelka A, Elvin K, Öst Å, Shizume Y, Furuya K, Löfberg R. Safety and tolerability of a modified filter-type device for leukocytapheresis using ACD-A as anticoagulant in patients with mild to moderately active ulcerative colitis. Results of a pilot study. J Clin Apher 2010; 25:287-93. [DOI: 10.1002/jca.20255] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Lindberg A, Eberhardson M, Karlsson M, Karlén P. Long-term follow-up with Granulocyte and Monocyte Apheresis re-treatment in patients with chronically active inflammatory bowel disease. BMC Gastroenterol 2010; 10:73. [PMID: 20604939 PMCID: PMC2914086 DOI: 10.1186/1471-230x-10-73] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2010] [Accepted: 07/06/2010] [Indexed: 12/12/2022] Open
Abstract
Background Patients with IBD and chronic inflammation refractory to conventional therapy often demonstrate higher risk of serious complications. Combinations of immunosuppression and biological treatment as well as surgical intervention are often used in this patient group. Hence, there is need for additional treatment options. In this observational study, focused on re-treatment and long-term results, Granulocyte/Monocyte Adsorption (GMA, Adacolumn®) treatment has been investigated to study efficacy, safety and quality of life in IBD-patients with chronic activity. Methods Fifteen patients with ulcerative colitis and 25 patients with Crohn's disease, both groups with chronically active inflammation refractory to conventional medication were included in this observational study. The patients received 5-10 GMA sessions, and the clinical activity was assessed at baseline, after each completed course, and at week 10 and 20 by disease activity index, endoscopy and quality of life evaluation. Relapsed patients were re-treated by GMA in this follow-up study up to 58 months. Results Clinical response was seen in 85% and complete remission in 65% of the patients. Ten patients in the UC-group (66%) and 16 patients in the CD-group (64%) maintained clinical and endoscopic remission for an average of 14 months. Fourteen patients who relapsed after showing initial remission were re-treated with GMA and 13 (93%) went into a second remission. Following further relapses, all of seven patients were successfully re-treated for the third time, all of three patients for the fourth time and one for a fifth time. Conclusions IBD-patients with chronic inflammation despite conventional therapy seem to benefit from GMA. Re-treatment of relapsing remission patients seems to be effective.
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Affiliation(s)
- Annelie Lindberg
- Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset SE-118 83 Stockholm, Sweden
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Adsorptive depletion of alpha4 integrin(hi)- and CX3CR1hi-expressing proinflammatory monocytes in patients with ulcerative colitis. Dig Dis Sci 2010; 55:1886-95. [PMID: 19908144 DOI: 10.1007/s10620-009-0974-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2009] [Accepted: 08/28/2009] [Indexed: 02/06/2023]
Abstract
BACKGROUND Two main functionally distinct monocytes phenotypes are known: the CD14(hi)CD16(-) "classical" and the CD14(+)CD16(+) "proinflammatory" phenotypes. The latter phenotype is elevated in patients with ulcerative colitis (UC) and is suspected to have a major role in the immunopathogenesis of UC. AIM To selectively deplete circulating proinflammatory CD14(+)CD16(+) monocyte phenotype. METHODS Seven corticosteroid-naïve patients with UC (clinical activity index = 8.7 +/- 1.3) and seven healthy subjects were included. In patients with UC, granulocyte/monocyte adsorption (GMA) was done with an Adacolumn that selectively adsorbs leucocytes of the myeloid lineage. Blood from all subjects at baseline and from the patients immediately after the first GMA session was processed. Isolated monocytes were subjected to fluorescence-activated cell sorter analyses. RESULTS The seven UC patients achieved remission (CAI <or=4) after 5-10 GMA sessions. GMA induced a strong fall in the ratio (%) of CD14(+)CD16(+) to CD14(hi)CD16(-) monocytes, from 10.0 +/- 1.4 to 3.0 +/- 0.9. Further, expressions of alpha4 integrin (374.8 +/- 26.1 mean fluorescence intensity, MFI) and CX(3)CR1 (49.5 +/- 4.6 MFI) were significantly high on CD14(+)CD16(+)monocytes as compared with on CD14(hi)CD16(-) monocytes (169.2 +/- 17.2 and 33.2 +/- 3.6 MFI, respectively). Additionally, GMA significantly increased the ratio of the CD14(hi)CD16(-)CCR2(low) "immature" monocytes from 3.74 +/- 0.62 to 8.11 +/- 0.56 MFI. CONCLUSIONS We found high expressions of alpha4 integrin and CX(3)CR1 on monocytes in patients with active UC, known to promote the extravasation of CD14(+)CD16(+) monocytes into the mucosa. GMA effectively depletes CD14(+)CD16(+) monocytes and concomitantly increases CD14(hi)CD16(-)CCR2(low) "immature" monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.
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Dignass AU, Eriksson A, Kilander A, Pukitis A, Rhodes JM, Vavricka S. Clinical trial: five or ten cycles of granulocyte-monocyte apheresis show equivalent efficacy and safety in ulcerative colitis. Aliment Pharmacol Ther 2010; 31:1286-95. [PMID: 20331579 DOI: 10.1111/j.1365-2036.2010.04295.x] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Ulcerative colitis is characterized by leucocyte infiltration into the colonic mucosa. Granulocyte-monocyte apheresis depletes these cells. AIM To assess the non-inferiority of 5-10 apheresis treatments in patients with steroid-dependent or steroid-refractory ulcerative colitis. METHODS A total of 196 adults with moderate-severe ulcerative colitis were randomized 1:1 to 5 (n = 96) or 10 (n = 90) open label apheresis treatments. The primary endpoint was non-inferiority of clinical activity index score after 12 weeks. RESULTS The intent-to-treat population comprised 82 and 80 patients for the 5- and 10-treatment groups, respectively. The difference between the two groups in mean clinical activity index was 0.24 with an upper 95% confidence interval of 1.17, which was below a predefined non-inferiority threshold of 1.33. Clinical activity index score improved from baseline in both groups (from 8.7 to 5.6 with 5 treatments, and from 8.8 to 5.4 with 10), with no significant difference between the groups (P = 0.200). Outcomes for the 5- and 10-treatment groups were similar--clinical remission: 44% and 40%, respectively (P = 0.636); clinical response: 56% and 59%, respectively (P = 0.753). The treatment was well tolerated in both groups. CONCLUSIONS This prospective study comparing apheresis regimens in ulcerative colitis demonstrates that 5 treatments were not inferior to 10 treatments in steroid-refractory or -dependent ulcerative colitis.
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Affiliation(s)
- A U Dignass
- Department of Medicine I, Markus-Krankenhaus, Frankfurt/Main, Germany.
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