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Published in: International Journal of Colorectal Disease 8/2011

01-08-2011 | Original Article

The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis

Authors: Mingming Zhu, Xitao Xu, Fang Nie, Jinlu Tong, Shudong Xiao, Zhihua Ran

Published in: International Journal of Colorectal Disease | Issue 8/2011

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Abstract

Purpose

The use of selective leukocytapheresis for the treatment of ulcerative colitis (UC) has been evaluated in several open and controlled trials, with varying outcomes. A meta-analysis was performed to better assess the efficacy and safety of selective leukocytapheresis as supplemental therapy compared with conventional pharmacotherapy in patients with UC.

Methods

All randomized trials comparing selective leukocytapheresis supplementation with conventional pharmacotherapy were included from electronic databases and reference lists. A meta-analysis that pooled the outcome effects of leukocytapheresis and pharmacotherapy was performed. A fixed effect model or random effect model was selected depending on the heterogeneity test of the trials.

Results

Nine randomized controlled trials met the inclusion criteria contributing a total of 686 participants. Compared with conventional pharmacotherapy, leukocytapheresis supplementation presented a significant benefit in promoting a response rate (OR, 2.88, 95% CI: 1.60–5.18) and remission rate (OR, 2.04; 95% CI, 1.36–3.07) together with significant higher steroid-sparing effects (OR, 10.49; 95% CI, 3.44–31.93) in patients with active moderate-to-severe UC by intention-to-treat analysis. Leukocytapheresis was more effective in maintaining clinical remission for asymptomatic UC patients than conventional therapy (OR, 8.14; 95% CI, 2.22–29.90). The incidence of mild–moderate adverse effects was much less frequent in the leukocytapheresis groups than conventional pharmacotherapy groups (OR, 0.16; 95% CI, 0.04–0.60). Few severe adverse events were observed.

Conclusions

Current data indicate that leukocytapheresis supplementation may be more efficacious on improving response and remission rates and tapering corticosteroid dosage with excellent tolerability and safety than conventional pharmacotherapy in patients with UC. In addition, more high-quality randomized controlled trials are required to confirm the higher efficacy of leukocytapheresis in patients with UC.
Literature
1.
go back to reference Rugtveit J, Brandtzaeg P, Halstensen TS (1994) Increased macrophage subsets in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut 35:669–674PubMedCrossRef Rugtveit J, Brandtzaeg P, Halstensen TS (1994) Increased macrophage subsets in inflammatory bowel disease: apparent recruitment from peripheral blood monocytes. Gut 35:669–674PubMedCrossRef
2.
go back to reference Meuret G, Bitzi A, Hammer B (1978) Macrophage turnover in Crohn's disease and ulcerative colitis. Gastroenterol 74:501–503 Meuret G, Bitzi A, Hammer B (1978) Macrophage turnover in Crohn's disease and ulcerative colitis. Gastroenterol 74:501–503
3.
go back to reference Mahida YR (1997) Monocytes and macrophages in inflammatory bowel disease. In: Allan RN, Rhodes JM, Hanauer SB, Keighley MRB, Alexander-Williams J, Fazio VW (eds) Inflamatory bowel diseases, 3rd edn. Churchill Livingstone, New York, pp 81–85 Mahida YR (1997) Monocytes and macrophages in inflammatory bowel disease. In: Allan RN, Rhodes JM, Hanauer SB, Keighley MRB, Alexander-Williams J, Fazio VW (eds) Inflamatory bowel diseases, 3rd edn. Churchill Livingstone, New York, pp 81–85
4.
go back to reference Sharon P, Stenson WF (1984) Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterol 86:453–460 Sharon P, Stenson WF (1984) Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterol 86:453–460
5.
go back to reference Balfour S (1994) Cytokines in inflammatory bowel disease: pathophysiology and clinical considerations. Gastroenterol 106:533–539 Balfour S (1994) Cytokines in inflammatory bowel disease: pathophysiology and clinical considerations. Gastroenterol 106:533–539
6.
go back to reference Nikolaus S, Bauditz J, Gionchetti P (1998) Increased secretion of proinflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut 42:470–476PubMedCrossRef Nikolaus S, Bauditz J, Gionchetti P (1998) Increased secretion of proinflammatory cytokines by circulating polymorphonuclear neutrophils and regulation by interleukin-10 during intestinal inflammation. Gut 42:470–476PubMedCrossRef
7.
go back to reference Kaplanski G, Marin V, Montero-Julian F (2003) IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 24:25–29PubMedCrossRef Kaplanski G, Marin V, Montero-Julian F (2003) IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 24:25–29PubMedCrossRef
8.
go back to reference Hanai H, Watanabe F, Takeuchi K et al (2003) Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study. Clin Gastroenterol Hepatol 1:28–35PubMedCrossRef Hanai H, Watanabe F, Takeuchi K et al (2003) Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study. Clin Gastroenterol Hepatol 1:28–35PubMedCrossRef
9.
go back to reference Rembacken BJ, Newbould HE, Richards SJ et al (1998) Granulocyte apheresis in inflammatory bowel disease: possible mechanisms of effect. Ther Apher 2:93–96PubMedCrossRef Rembacken BJ, Newbould HE, Richards SJ et al (1998) Granulocyte apheresis in inflammatory bowel disease: possible mechanisms of effect. Ther Apher 2:93–96PubMedCrossRef
10.
go back to reference Ayabe T, Ashida T, Taniguchi M et al (1997) A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis. Intern Med 36:322–326PubMedCrossRef Ayabe T, Ashida T, Taniguchi M et al (1997) A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis. Intern Med 36:322–326PubMedCrossRef
11.
go back to reference Saniabadi AR, Hanai H, Takeuchi K et al (2003) Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial 7:48–59PubMedCrossRef Saniabadi AR, Hanai H, Takeuchi K et al (2003) Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of inflammatory and refractory diseases associated with leukocytes. Ther Apher Dial 7:48–59PubMedCrossRef
12.
go back to reference Hiraishi K, Takeda Y, Shiobara N et al (2003) Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Ther Apher Dial 7:334–340PubMedCrossRef Hiraishi K, Takeda Y, Shiobara N et al (2003) Studies on the mechanisms of leukocyte adhesion to cellulose acetate beads: an in vitro model to assess the efficacy of cellulose acetate carrier-based granulocyte and monocyte adsorptive apheresis. Ther Apher Dial 7:334–340PubMedCrossRef
13.
go back to reference Sawada K, Ohnishi K, Kosaka T et al (1997) Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis. Ther Apher 1:207–211PubMedCrossRef Sawada K, Ohnishi K, Kosaka T et al (1997) Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis. Ther Apher 1:207–211PubMedCrossRef
14.
go back to reference Bresci G, Parisi G, Mazzoni A, Scatena F, Capria A (2007) Treatment of patients with acute ulcerative colitis: conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): a pilot study. Dig Liver Dis 39:430–434PubMedCrossRef Bresci G, Parisi G, Mazzoni A, Scatena F, Capria A (2007) Treatment of patients with acute ulcerative colitis: conventional corticosteroid therapy (MP) versus granulocytapheresis (GMA): a pilot study. Dig Liver Dis 39:430–434PubMedCrossRef
15.
go back to reference Domènech E, Hinojosa J, Esteve-Comas M et al (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20:1347–1352PubMedCrossRef Domènech E, Hinojosa J, Esteve-Comas M et al (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20:1347–1352PubMedCrossRef
16.
go back to reference Shimoyama T, Sawada K, Tanaka T et al (1999) Granulocyte and monocyte apheresis with the G-1 column in the treatment of patients with active ulcerative colitis. Jpn J Apher 18:117–131 Shimoyama T, Sawada K, Tanaka T et al (1999) Granulocyte and monocyte apheresis with the G-1 column in the treatment of patients with active ulcerative colitis. Jpn J Apher 18:117–131
17.
go back to reference Sawada K, Muto T, Shimoyama T et al (2003) Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column. Curr Pharm Des 9:307–321PubMedCrossRef Sawada K, Muto T, Shimoyama T et al (2003) Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column. Curr Pharm Des 9:307–321PubMedCrossRef
18.
go back to reference Kjaergard LL, Villumsen J, Gluud C (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135:982–989PubMed Kjaergard LL, Villumsen J, Gluud C (2001) Reported methodologic quality and discrepancies between large and small randomized trials in meta-analyses. Ann Intern Med 135:982–989PubMed
19.
go back to reference Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634PubMed
20.
go back to reference Hanai H, Watanabe F, Yamada M et al (2004) Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion 70:36–44PubMedCrossRef Hanai H, Watanabe F, Yamada M et al (2004) Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion 70:36–44PubMedCrossRef
21.
go back to reference Nakamura T, Kawagoe Y, Matsuda T et al (2004) Effect of granulocyte and monocyte adsorption apheresis on urinary albumin excretion and plasma endothelin-1 concentration in patients with active ulcerative colitis. Blood Purif 22:499–504PubMedCrossRef Nakamura T, Kawagoe Y, Matsuda T et al (2004) Effect of granulocyte and monocyte adsorption apheresis on urinary albumin excretion and plasma endothelin-1 concentration in patients with active ulcerative colitis. Blood Purif 22:499–504PubMedCrossRef
22.
go back to reference Bresci G, Parisi G, Mazzoni A, Scatena F, Capria A (2008) Granulocytapheresis versus methylprednisolone in patients with acute ulcerative colitis: 12-month follow up. J Gastroenterol Hepatol 23:1678–1682PubMedCrossRef Bresci G, Parisi G, Mazzoni A, Scatena F, Capria A (2008) Granulocytapheresis versus methylprednisolone in patients with acute ulcerative colitis: 12-month follow up. J Gastroenterol Hepatol 23:1678–1682PubMedCrossRef
23.
go back to reference Hanai H, Iida T, Takeuchi K et al (2008) Intensive granulocyte and monocyte adsorption versus intravenous prednisolone in patients with severe ulcerative colitis: an unblinded randomised multi-centre controlled study. Dig Liver Dis 40:433–440PubMedCrossRef Hanai H, Iida T, Takeuchi K et al (2008) Intensive granulocyte and monocyte adsorption versus intravenous prednisolone in patients with severe ulcerative colitis: an unblinded randomised multi-centre controlled study. Dig Liver Dis 40:433–440PubMedCrossRef
24.
go back to reference Sands BE, Sandborn WJ, Feagan B et al (2008) A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterol 135:400–409CrossRef Sands BE, Sandborn WJ, Feagan B et al (2008) A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterol 135:400–409CrossRef
25.
go back to reference Maiden L, Takeuchi K, Baur R et al (2008) Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse. Inflamm Bowel Dis 14:1413–1418PubMedCrossRef Maiden L, Takeuchi K, Baur R et al (2008) Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse. Inflamm Bowel Dis 14:1413–1418PubMedCrossRef
26.
go back to reference Emmrich J, Petermann S, Nowak D et al (2007) Leukocytapheresis (LCAP) in the management of chronic active ulcerative colitis–results of a randomized pilot trial. Dig Dis Sci 52:2044–2053PubMedCrossRef Emmrich J, Petermann S, Nowak D et al (2007) Leukocytapheresis (LCAP) in the management of chronic active ulcerative colitis–results of a randomized pilot trial. Dig Dis Sci 52:2044–2053PubMedCrossRef
27.
go back to reference Sakuraba A, Motoya S, Watanabe K et al (2009) An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment. Am J Gastroenterol 104:2990–2995PubMedCrossRef Sakuraba A, Motoya S, Watanabe K et al (2009) An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment. Am J Gastroenterol 104:2990–2995PubMedCrossRef
28.
go back to reference Sakata Y, Iwakiri R, Amemori S et al (2008) Comparison of the efficacy of granulocyte and monocyte/macrophage adsorptive apheresis and leukocytapheresis in active ulcerative colitis patients: a prospective randomized study. Eur J Gastroenterol Hepatol 20:629–633PubMedCrossRef Sakata Y, Iwakiri R, Amemori S et al (2008) Comparison of the efficacy of granulocyte and monocyte/macrophage adsorptive apheresis and leukocytapheresis in active ulcerative colitis patients: a prospective randomized study. Eur J Gastroenterol Hepatol 20:629–633PubMedCrossRef
29.
go back to reference Hidaka T, Suzuki K, Kawakami M et al (2001) Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis. J Clin Apher 16:74–81PubMedCrossRef Hidaka T, Suzuki K, Kawakami M et al (2001) Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis. J Clin Apher 16:74–81PubMedCrossRef
30.
go back to reference Shimoyama T, Sawada K, Hiwatashi N et al (2001) Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher 16:1–9PubMedCrossRef Shimoyama T, Sawada K, Hiwatashi N et al (2001) Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher 16:1–9PubMedCrossRef
31.
go back to reference Sawada K, Kusugami K, Suzuki Y et al (2005) Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment. Am J Gastroenterol 100:1362–1369PubMedCrossRef Sawada K, Kusugami K, Suzuki Y et al (2005) Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case-control study with sham apheresis as placebo treatment. Am J Gastroenterol 100:1362–1369PubMedCrossRef
32.
go back to reference Hibi T, Sakuraba A (2005) Is there a role for apheresis in gastrointestinal disorders? Nat Clin Pract Gastroenterol Hepatol 2:200–201PubMedCrossRef Hibi T, Sakuraba A (2005) Is there a role for apheresis in gastrointestinal disorders? Nat Clin Pract Gastroenterol Hepatol 2:200–201PubMedCrossRef
Metadata
Title
The efficacy and safety of selective leukocytapheresis in the treatment of ulcerative colitis: a meta-analysis
Authors
Mingming Zhu
Xitao Xu
Fang Nie
Jinlu Tong
Shudong Xiao
Zhihua Ran
Publication date
01-08-2011
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 8/2011
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-011-1193-9

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