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Published in: BMC Gastroenterology 1/2014

Open Access 01-12-2014 | Research article

Therapeutic effect of intensive granulocyte and monocyte adsorption apheresis combined with thiopurines for steroid- and biologics-naïve Japanese patients with early-diagnosed Crohn’s disease

Authors: Takumi Fukuchi, Hiroshi Nakase, Satoshi Ubukata, Minoru Matsuura, Takuya Yoshino, Takahiko Toyonaga, Keiji Shimazu, Hideaki Koga, Hiroshi Yamashita, Dai Ito, Kiyoshi Ashida

Published in: BMC Gastroenterology | Issue 1/2014

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Abstract

Background

Early induction with biologics can reduce complications in patients with Crohn’s disease (CD) and improve their quality of life. The safety of biologics, however, is uncertain. Granulocyte and monocyte adsorptive apheresis (GMAA) is a natural biologic therapy that selectively removes granulocytes and monocytes/macrophages and has few severe adverse effects. The effects of GMAA on patients with early-diagnosed CD are unclear. We investigated the effects of GMAA combined with thiopurines on patients with early-diagnosed CD.

Methods

Twenty-two corticosteroid- and biologic-naïve patients with active early-diagnosed CD were treated with intensive GMAA (twice per week) combined with thiopurines administration. Active early-diagnosed CD was defined as follows: (i) within 2years after diagnosis of CD, (ii) with no history of both surgical treatment and endoscopic dilation therapy, and (iii) Crohn’s Disease Activity Index (CDAI) was higher than 200. We investigated the ratios of clinical remission defined as CDAI was less than or equal to 150 at 2, 4, 6 and 52weeks and mucosal healing defined as a Simplified Endoscopic Activity Score for Crohn’s Disease (SES-CD) as 0 at 6 and 52weeks. Adverse events were recorded at each visit.

Results

The ratios of clinical remission at 2, 4, and 6 weeks were 6 of 22 (27.2%), 12 of 22 (54.5%), and 17 of 22 (77.2%), respectively. At 52 weeks, 18 of 21 patients (81.8%) were in clinical remission. The ratios of mucosal healing at 6 and 52 weeks were 5 of 22 (22.7%) and 11 of 22 (50%), respectively. The difference in the mucosal healing ratio was significant between 6 and 52 weeks (p = 0.044). No serious adverse effects were observed during this study.

Conclusions

Combination therapy with intensive GMAA and thiopurines administration rapidly induced high remission in patients with active early-diagnosed CD without serious adverse effect. Mucosal healing was observed in 50.0% of enrolled patients. This combination therapy might be a rational option for patients with early-diagnosed CD.
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Literature
1.
go back to reference Summers RW, Switz DM, Sessions JT, Becktel JM, Best WR, Kern FJR, Singleton JW: National cooperative Crohn’s disease study: results of drug treatment. Gastroenterology. 1979, 77: 847-869.PubMed Summers RW, Switz DM, Sessions JT, Becktel JM, Best WR, Kern FJR, Singleton JW: National cooperative Crohn’s disease study: results of drug treatment. Gastroenterology. 1979, 77: 847-869.PubMed
2.
go back to reference Malchow H, Ewe K, Brandes JW, Goebell H, Ehms H, Sommer H, Jesdinsky H: European Cooperative Crohn’s Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984, 86: 249-266.PubMed Malchow H, Ewe K, Brandes JW, Goebell H, Ehms H, Sommer H, Jesdinsky H: European Cooperative Crohn’s Disease Study (ECCDS): results of drug treatment. Gastroenterology. 1984, 86: 249-266.PubMed
3.
go back to reference Faubion WA, Loftus EV, Harmsen WS, Zinsmeister AR, Sandborn WJ: The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001, 121: 255-260.CrossRefPubMed Faubion WA, Loftus EV, Harmsen WS, Zinsmeister AR, Sandborn WJ: The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study. Gastroenterology. 2001, 121: 255-260.CrossRefPubMed
4.
5.
go back to reference D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van de Mierop FJ, Coche JC, van der Woude J, Ochsenkühn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomized trial. Lancet. 2008, 371: 660-667.CrossRefPubMed D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van de Mierop FJ, Coche JC, van der Woude J, Ochsenkühn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D: Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomized trial. Lancet. 2008, 371: 660-667.CrossRefPubMed
6.
go back to reference Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, Braun J, Reed E, Gjertson D, Singh RR: TNFα blocker in human disease: An overview of efficacy and safety. Clin Immunol. 2008, 126: 13-30.CrossRefPubMed Lin J, Ziring D, Desai S, Kim S, Wong M, Korin Y, Braun J, Reed E, Gjertson D, Singh RR: TNFα blocker in human disease: An overview of efficacy and safety. Clin Immunol. 2008, 126: 13-30.CrossRefPubMed
7.
go back to reference Lakatos PL, Golovics PA, David G, Pandur T, Erdelyi Z, Horvath A, Mester G, Balogh M, Szipocs I, Molnar C, Komaromi E, Veres G, Lovasz BD, Szathmari M, Kiss LS, Lakatos L: Has there been a change in the natural history of Crohn’s disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009. Am J Gastroenterol. 2012, 107: 579-588.CrossRefPubMed Lakatos PL, Golovics PA, David G, Pandur T, Erdelyi Z, Horvath A, Mester G, Balogh M, Szipocs I, Molnar C, Komaromi E, Veres G, Lovasz BD, Szathmari M, Kiss LS, Lakatos L: Has there been a change in the natural history of Crohn’s disease? Surgical rates and medical management in a population-based inception cohort from Western Hungary between 1977-2009. Am J Gastroenterol. 2012, 107: 579-588.CrossRefPubMed
8.
go back to reference Shimoyama T, Sawada K, Hiwatashi N, Sawada T, Matsueda K, Munakata A, Asakura H, Tanaka T, Kasukawa R, Kimura K, Suzuki Y, Nagamachi Y, Muto T, Nagawa H, Iizuka B, Baba S, Nasu M, Kataoka T, Kashiwagi N, Saniabadi AR: Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher. 2001, 16: 1-9.CrossRefPubMed Shimoyama T, Sawada K, Hiwatashi N, Sawada T, Matsueda K, Munakata A, Asakura H, Tanaka T, Kasukawa R, Kimura K, Suzuki Y, Nagamachi Y, Muto T, Nagawa H, Iizuka B, Baba S, Nasu M, Kataoka T, Kashiwagi N, Saniabadi AR: Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher. 2001, 16: 1-9.CrossRefPubMed
9.
go back to reference Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, Shima C, Bjarnason I, Lofberg R: Adacolumn an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of on inflammatory and refractory disease associate with leucocytes. Ther Apher Dial. 2003, 7: 48-59.CrossRefPubMed Saniabadi AR, Hanai H, Takeuchi K, Umemura K, Nakashima M, Adachi T, Shima C, Bjarnason I, Lofberg R: Adacolumn an adsorptive carrier based granulocyte and monocyte apheresis device for the treatment of on inflammatory and refractory disease associate with leucocytes. Ther Apher Dial. 2003, 7: 48-59.CrossRefPubMed
10.
go back to reference Hanai H, Watanabe F, Takeuchi K, Iida T, Yamada M, Iwaoka Y, Saniabadi A, Matsushita I, Sato Y, Tozawa K, Arai H, Furuta T, Sugimoto K, Bjarnason I: Leukocyte adsorption apheresis for the treatment of active ulcerative colitis: a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol. 2003, 1: 28-35.CrossRefPubMed Hanai H, Watanabe F, Takeuchi K, Iida T, Yamada M, Iwaoka Y, Saniabadi A, Matsushita I, Sato Y, Tozawa K, Arai H, Furuta T, Sugimoto K, Bjarnason I: Leukocyte adsorption apheresis for the treatment of active ulcerative colitis: a prospective uncontrolled pilot study. Clin Gastroenterol Hepatol. 2003, 1: 28-35.CrossRefPubMed
11.
go back to reference Sakuraba A, Motoya S, Watanabe K, Nishishita M, Kanke K, Matsui T, Suzuki Y, Oshima T, Kunisaki R, Matsumoto T, Hanai H, Fukunaga K, Yoshimura N, Chiba T, Funakoshi S, Aoyama N, Andoh A, Nakase H, Mizuta Y, Suzuki R, Akamatsu T, Iizuka M, Ashida T, Hibi T: 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. 2009, 104: 2990-2995.CrossRefPubMed Sakuraba A, Motoya S, Watanabe K, Nishishita M, Kanke K, Matsui T, Suzuki Y, Oshima T, Kunisaki R, Matsumoto T, Hanai H, Fukunaga K, Yoshimura N, Chiba T, Funakoshi S, Aoyama N, Andoh A, Nakase H, Mizuta Y, Suzuki R, Akamatsu T, Iizuka M, Ashida T, Hibi T: 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. 2009, 104: 2990-2995.CrossRefPubMed
12.
go back to reference Fukuchi T, Nakase H, Ito D, Yamashita H, Matsuura M, Nagatani Y, Koga H, Senda K, Eguchi T, Ubukata S, Kawaguchi S, Ueda A, Tanaka T, Ohashi R, Otzuka M, Ashida K: Rapid induction of mucosal healing by intensive granulocyte and monocyte adsorptive apheresis in active ulcerative colitis patients without concomitant corticosteroid therapy. Aliment Pharmacol Ther. 2011, 34: 583-585.CrossRefPubMed Fukuchi T, Nakase H, Ito D, Yamashita H, Matsuura M, Nagatani Y, Koga H, Senda K, Eguchi T, Ubukata S, Kawaguchi S, Ueda A, Tanaka T, Ohashi R, Otzuka M, Ashida K: Rapid induction of mucosal healing by intensive granulocyte and monocyte adsorptive apheresis in active ulcerative colitis patients without concomitant corticosteroid therapy. Aliment Pharmacol Ther. 2011, 34: 583-585.CrossRefPubMed
13.
go back to reference Hanai H, Watanabe F, Yamada M, Sato Y, Takeuchi K, Iida T, Tozawa K, Tanaka T, Maruyama Y, Matsushita I, Iwaoka Y, Kikuchi K, Saniabadi AR: Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion. 2004, 70: 36-44.CrossRefPubMed Hanai H, Watanabe F, Yamada M, Sato Y, Takeuchi K, Iida T, Tozawa K, Tanaka T, Maruyama Y, Matsushita I, Iwaoka Y, Kikuchi K, Saniabadi AR: Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion. 2004, 70: 36-44.CrossRefPubMed
14.
go back to reference Kanke K, Nakano M, Hiraishi H, Terano A: Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liver Dis. 2004, 36: 811-817.CrossRefPubMed Kanke K, Nakano M, Hiraishi H, Terano A: Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liver Dis. 2004, 36: 811-817.CrossRefPubMed
15.
go back to reference Best WR, Becktel JM, Singleton JW, Kern F: Development of a Crohn’s disease activity index. Gastroenterology. 1976, 70: 439-444.PubMed Best WR, Becktel JM, Singleton JW, Kern F: Development of a Crohn’s disease activity index. Gastroenterology. 1976, 70: 439-444.PubMed
16.
go back to reference 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 Crohn’s Colitis. 2013, 7: 803-811.CrossRef 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 Crohn’s Colitis. 2013, 7: 803-811.CrossRef
17.
go back to reference Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P: Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004, 60: 505-512.CrossRefPubMed Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P: Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004, 60: 505-512.CrossRefPubMed
18.
go back to reference Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, Stokkers P, Hommes D, Rutgeerts P, Vermeire S, D'Haens G: Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010, 138: 463-468.CrossRefPubMed Baert F, Moortgat L, Van Assche G, Caenepeel P, Vergauwe P, De Vos M, Stokkers P, Hommes D, Rutgeerts P, Vermeire S, D'Haens G: Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010, 138: 463-468.CrossRefPubMed
19.
go back to reference Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P: Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010, 362: 1383-1395.CrossRefPubMed Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P: Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010, 362: 1383-1395.CrossRefPubMed
20.
go back to reference Fukuda Y, Matsui T, Suzuki Y, Kanke K, Matsumoto T, Takazoe M, Matsumoto T, Motoya S, Honma T, Sawada K, Yao T, Shimoyama T, Hibi T: Adsorptive granulocyte and monocyte apheresis for refractory Crohn’s disease: an open multicenter prospective study. J Gastroenterol. 2004, 39: 1158-1164.CrossRefPubMed Fukuda Y, Matsui T, Suzuki Y, Kanke K, Matsumoto T, Takazoe M, Matsumoto T, Motoya S, Honma T, Sawada K, Yao T, Shimoyama T, Hibi T: Adsorptive granulocyte and monocyte apheresis for refractory Crohn’s disease: an open multicenter prospective study. J Gastroenterol. 2004, 39: 1158-1164.CrossRefPubMed
21.
go back to reference Ljung T, Thomsen OØ, Vatn M, Karlén P, Karlsen LN, Tysk C, Nilsson SU, Kilander A, Gillberg R, Grip O, Lindgren S, Befrits R, Löfberg R: Granulocyte and monocyte/macrophage apheresis for inflammatory bowel disease: the first 100 patients treated in Scandinavia. Scand J Gastroenterol. 2007, 42: 221-227.CrossRefPubMed Ljung T, Thomsen OØ, Vatn M, Karlén P, Karlsen LN, Tysk C, Nilsson SU, Kilander A, Gillberg R, Grip O, Lindgren S, Befrits R, Löfberg R: Granulocyte and monocyte/macrophage apheresis for inflammatory bowel disease: the first 100 patients treated in Scandinavia. Scand J Gastroenterol. 2007, 42: 221-227.CrossRefPubMed
22.
go back to reference Bresci G, Romano A, Mazzoni A, Scatena F, Altomare E, Capria A, Sacco R: Feasibility and safety of granulocytapheresis in Crohn’s disease: a prospective cohort study. Gastroenterol Clin Biol. 2010, 34: 682-686.CrossRefPubMed Bresci G, Romano A, Mazzoni A, Scatena F, Altomare E, Capria A, Sacco R: Feasibility and safety of granulocytapheresis in Crohn’s disease: a prospective cohort study. Gastroenterol Clin Biol. 2010, 34: 682-686.CrossRefPubMed
23.
go back to reference Bouhnik Y, Lémann M, Mary JY, Scemama G, Taï R, Matuchansky C, Modigliani R, Rambaud JC: Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996, 347: 215-219.CrossRefPubMed Bouhnik Y, Lémann M, Mary JY, Scemama G, Taï R, Matuchansky C, Modigliani R, Rambaud JC: Long-term follow-up of patients with Crohn’s disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996, 347: 215-219.CrossRefPubMed
24.
go back to reference Cosnes J, Bourrier A, Laharie D, Nahon S, Bouhnik Y, Carbonnel F, Allez M, Dupas JL, Reimund JM, Savoye G, Jouet P, Moreau J, Mary JY, Colombel JF: Early administration of azathioprine vs conventional management of Crohn’s disease: a randomized controlled trial. Gastroenterology. 2013, 145: 758-765.CrossRefPubMed Cosnes J, Bourrier A, Laharie D, Nahon S, Bouhnik Y, Carbonnel F, Allez M, Dupas JL, Reimund JM, Savoye G, Jouet P, Moreau J, Mary JY, Colombel JF: Early administration of azathioprine vs conventional management of Crohn’s disease: a randomized controlled trial. Gastroenterology. 2013, 145: 758-765.CrossRefPubMed
25.
go back to reference Panés J, López-Sanromán A, Bermejo F, García-Sánchez V, Esteve M, Torres Y, Domènech E, Piqueras M, Gomez-García M, Gutiérrez A, Taxonera C, Sans M: Early azathioprine therapy is no effective than placebo for newly diagnosed Crohn’s disease. Gastroenterology. 2013, 145: 766-774.CrossRefPubMed Panés J, López-Sanromán A, Bermejo F, García-Sánchez V, Esteve M, Torres Y, Domènech E, Piqueras M, Gomez-García M, Gutiérrez A, Taxonera C, Sans M: Early azathioprine therapy is no effective than placebo for newly diagnosed Crohn’s disease. Gastroenterology. 2013, 145: 766-774.CrossRefPubMed
26.
go back to reference Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M: Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990, 99: 956-963.CrossRefPubMed Rutgeerts P, Geboes K, Vantrappen G, Beyls J, Kerremans R, Hiele M: Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990, 99: 956-963.CrossRefPubMed
27.
go back to reference D’Haens G, Geboes K, Rutgeerts P: Endoscopic and histologic healing of Crohn’s (ileo-) colitis with azathioprine. Gastrointest Endosc. 1999, 50: 667-671.CrossRefPubMed D’Haens G, Geboes K, Rutgeerts P: Endoscopic and histologic healing of Crohn’s (ileo-) colitis with azathioprine. Gastrointest Endosc. 1999, 50: 667-671.CrossRefPubMed
28.
go back to reference Toruner M, Loftus EV, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, Colombel JF, Egan LJ: Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008, 134: 929-936.CrossRefPubMed Toruner M, Loftus EV, Harmsen WS, Zinsmeister AR, Orenstein R, Sandborn WJ, Colombel JF, Egan LJ: Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology. 2008, 134: 929-936.CrossRefPubMed
Metadata
Title
Therapeutic effect of intensive granulocyte and monocyte adsorption apheresis combined with thiopurines for steroid- and biologics-naïve Japanese patients with early-diagnosed Crohn’s disease
Authors
Takumi Fukuchi
Hiroshi Nakase
Satoshi Ubukata
Minoru Matsuura
Takuya Yoshino
Takahiko Toyonaga
Keiji Shimazu
Hideaki Koga
Hiroshi Yamashita
Dai Ito
Kiyoshi Ashida
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2014
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/1471-230X-14-124

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