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Leukocytapheresis for the treatment of IBD

Abstract

Leukocytapheresis is a controversial nonpharmacologic treatment for IBD, in which white blood cells—the effector cells of the inflammatory process—are mechanically removed from the circulation. Current controversy centers on the uncontrolled nature of the leukocytapheresis trials performed and their use of different outcome measures in patient groups that have very variable disease activity and severity. Nonetheless, the efficacy data obtained are generally quite consistent: an excellent response (remission >80%) has been achieved in corticosteroid-naïve patients with ulcerative colitis and an average remission rate of more than 50% has been achieved in patients who have steroid-dependent or refractory ulcerative colitis. Interestingly, the largest randomized, double-blind, sham-controlled study of granulocyte–monocyte apheresis in patients with moderate to severe ulcerative colitis failed to demonstrate efficacy for the induction of clinical remission or response. Regardless, leukocytapheresis seems to be remarkably safe. The precise positioning of leukocytapheresis in the treatment of ulcerative colitis is uncertain at present and will vary according to geography and patient preference for a safe, nonpharmacologic treatment. Further efficacy studies are required to assess what the optimal number and frequency of treatments is, in addition to the need for head-to-head comparisons with established drugs.

Key Points

  • Enthusiasm for the use of leukocytapheresis in the treatment of patients with IBD (mainly ulcerative colitis) is fueled by the lack of serious adverse effects and tempered by the lack of conventional placebo-controlled data or head-to-head comparisons with potential competitors

  • Leukocytapheresis induces clinical remission in more than 80% of corticosteroid-naïve patients who have ulcerative colitis

  • Average remission rates are in excess of 50% in patients with moderate or severe ulcerative colitis and in patients with corticosteroid-dependent or corticosteroid-resistant ulcerative colitis

  • Data in Crohn's disease are sparse and further studies are required

  • Leukocyte apheresis clearly has potential use in patients with ulcerative colitis, but to decide its precise positioning in treatment algorithms will require targeted studies

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References

  1. Bjarnason I et al. (1993) Non-steroidal anti-inflammatory drugs and Crohn's disease. In Inflammatory Bowel Diseases: Pathophysiology as Basis of Treatment, 208–222 (Eds Scholmeric J) Falk Symposium No 67. Lancaster: Kluwer Academic Publishers

    Google Scholar 

  2. Tibble J et al. (2000) Surrogate markers of intestinal inflammation are predictive for relapse in patients with inflammatory bowel disease. Gastroenterology 119: 15–22

    CAS  Article  Google Scholar 

  3. Kozuch PL and Hanauer SB (2008) Treatment of inflammatory bowel disease: a review of medical therapy. World J Gastroenterol 14: 354–377

    CAS  Article  Google Scholar 

  4. Yamamoto-Furusho JK (2007) Innovative therapeutics for inflammatory bowel disease. World J Gastroenterol 13: 1893–1896

    CAS  Article  Google Scholar 

  5. Brown SL et al. (2002) Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration. Arthritis Rheum 46: 3151–3158

    CAS  Article  Google Scholar 

  6. Gomez-Reino JJ et al. (2003) Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report. Arthritis Rheum 48: 2122–2127

    CAS  Article  Google Scholar 

  7. Sandborn WJ et al. (2005) Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med 353: 1912–1925

    CAS  Article  Google Scholar 

  8. Seegers D et al. (2002) Review article: a critical approach to new forms of treatment of Crohn's disease and ulcerative colitis. Aliment Pharmacol Ther 16 (Suppl 4): 53–58

    Article  Google Scholar 

  9. Morse EE et al. (1966) Repeated leukapheresis of patients with chronic myelocytic leukemia. Transfusion 6: 175–182

    Article  Google Scholar 

  10. Buckner D et al. (1969) Leukapheresis by continous flow centrifugation (CFC) in patients with chronic myelocytic leukemia (CML). Blood 33: 353–369

    CAS  PubMed  Google Scholar 

  11. Curtis JE et al. (1972) Leukoapheresis therapy of chronic lymphocytic leukemia. Blood 39: 163–175

    CAS  PubMed  Google Scholar 

  12. Ohara M et al. (1997) Granulocytapheresis in the treatment of patients with rheumatoid arthritis. Artif Organs 2: 989–994

    Google Scholar 

  13. Shimoyama T 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: 1–9

    CAS  Article  Google Scholar 

  14. Lazarus HM (1991) Selective in vivo removal of rheumatoid factor by an extracorporeal treatment device in rheumatoid arthritis patients. Transfusion 31: 122–128

    CAS  Article  Google Scholar 

  15. Bicks RO et al. (1985) The treatment of severe chronically active Crohn's disease by T8 (suppressor cell) lymphapheresis. Gastroenterology 88: A1325

    Google Scholar 

  16. Bicks RO et al. (1987) Total parenteral nutrition (TPN) plus T-lymphocyte apheresis (TLA) in the treatment of severe chronic active Crohn's disease. Gastroenterology 94: A34

    Google Scholar 

  17. Sato T KN et al. (1991) Improved on-line thoracic duct drainage for lymphocytapheresis. Int J Artif Organs 14: 800–804

    Article  Google Scholar 

  18. Hidaka T and Suzuki K (1997) Efficacy of filtration leukocytapheresis on rheumatoid arthritis with vasculitis. Ther Apher 1: 212–214

    CAS  Article  Google Scholar 

  19. Onuma S et al. (2006) Investigation of the clinical effect of large volume leukocytapheresis on methotrexate-resistant rheumatoid arthritis. Ther Apher Dial 10: 404–411

    Article  Google Scholar 

  20. Kashiwagi N et al. (1998) A role for granulocyte and monocyte apheresis in the treatment of rheumatoid arthritis. Ther Apher 2: 134–141

    CAS  Article  Google Scholar 

  21. Muratov V et al. (2006) Downregulation of interferon-γ parallels clinical response to selective leukocyte apheresis in patients with inflammatory bowel disease: a 12-month follow-up study. Int J Colorectal Dis 21: 493–504

    CAS  Article  Google Scholar 

  22. Saniabadi AR et al. (2007) Therapeutic leukocytapheresis for inflammatory bowel disease. Transfus Apher Sci 37: 191–200

    Article  Google Scholar 

  23. Hanai H et al. (2008) Adsorptive depletion of elevated proinflammatory CD14+CD16+DR++ monocytes in patients with inflammatory bowel disease. Am J Gastroenterol 103: 1213–1216

    Article  Google Scholar 

  24. Saniabadi AR et al. (2005) Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: an adjunct or an alternative to drug therapy. J Clin Apher 3: 171–184

    Article  Google Scholar 

  25. Saniabadi AR 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 1: 48–59

    Article  Google Scholar 

  26. Hanai H et al. (2002) Therapeutic efficacy of granulocyte and monocyte adsorption apheresis in severe active ulcerative colitis. Dig Dis Sci 47: 2349–2353

    Article  Google Scholar 

  27. Yokoyama Y et al. (2007) Demonstration of low-regulatory CD25High+CD4+ and high-pro-inflammatory CD28CD4+ T-cell subsets in patients with ulcerative colitis: modified by selective granulocyte and monocyte adsorption apheresis. Dig Dis Sci 52: 2725–2731

    Article  Google Scholar 

  28. Aoki H et al. (2007) Adacolumn selective leukocyte adsorption apheresis in patients with active ulcerative colitis: clinical efficacy, effects on plasma IL-8 and the expression of Toll-like receptor 2 on granulocytes. Dig Dis Sci 52: 1427–1433

    CAS  Article  Google Scholar 

  29. Hanai H et al. (2006) Effects of Adacolumn selective leukocytapheresis on plasma cytokines during active disease in patients with ulcerative colitis. World J Gastroenterol 12: 3393–3399

    CAS  Article  Google Scholar 

  30. Hanai H et al. (2004) Correlation of serum soluble TNF-alpha receptors I and II levels with disease activity in patients with ulcerative colitis. Am J Gastroenterol 99: 1532–1538

    CAS  Article  Google Scholar 

  31. Yamamoto T et al. (2006) Impact of selective leukocytapheresis on mucosal inflammation and ulcerative colitis: cytokine profiles and endoscopic findings. Inflamm Bowel Dis 12: 719–726

    Article  Google Scholar 

  32. Lerebours E et al. (1994) Treatment of Crohn's disease by lymphocyte apheresis: a randomized controlled trial. Groupe d'Etudes Thérapeutiques des Affections Inflammatoires Digestives. Gastroenterology 107: 357–361

    CAS  Article  Google Scholar 

  33. Ayabe T et al. (1997) A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis. Intern Med 36: 322–326

    CAS  Article  Google Scholar 

  34. Ayabe T et al. (1998) Centrifugal leukocyte apheresis for ulcerative colitis. Ther Apher 2: 125–128

    CAS  Article  Google Scholar 

  35. Kohgo Y et al. (2002) Leukocyte apheresis using a centrifugal cell separator in refractory ulcerative colitis; A multicenter open label trial. Ther Apher 6: 255–260

    CAS  Article  Google Scholar 

  36. Sawada K et al. (2003) Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column. Curr Pharm 9: 307–321

    CAS  Article  Google Scholar 

  37. Kanke K et al. (2004) Clinical evaluation of granulocyte/monocyte apheresis therapy for active ulcerative colitis. Dig Liver Dis 36: 811–817

    CAS  Article  Google Scholar 

  38. Kanai T et al. (2006) The logics of leukocytapheresis as a natural biological therapy for inflammatory bowel disease. Expert Opin Biol Ther 6: 453–466

    CAS  Article  Google Scholar 

  39. Hanai H et al. (2003) Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study. Clin Gastroenterol Hepatol 1: 28–35

    Article  Google Scholar 

  40. Hanai H (2006) Positions of selective leukocytapheresis in the medical therapy of ulcerative colitis. World J Gastroenterol 12: 7568–7577

    Article  Google Scholar 

  41. Naganuma M et al. (2004) Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis 10: 251–257

    Article  Google Scholar 

  42. Tomomasa T et al. (2003) Granulocyte adsorptive apheresis for pediatric patients with ulcerative colitis. Dig Dis Sci 48: 750–754

    Article  Google Scholar 

  43. Yamamoto T et al. (2004) Granulocyte and monocyte adsorptive apheresis in the treatment of active distal ulcerative colitis: a prospective, pilot study. Aliment Pharmacol Ther 20: 783–792

    CAS  Article  Google Scholar 

  44. Honma T et al. (2005) Leukocytapheresis is effective in inducing but not in maintaining remission in ulcerative colitis. J Clin Gastroenterol 39: 886–890

    Article  Google Scholar 

  45. Domenech E et al. (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20: 1347–1352

    CAS  Article  Google Scholar 

  46. Ljung T et al. (2007) Granulocyte, monocyte/macrophage apheresis for inflammatory bowel disease: the first 100 patients treated in Scandinavia. Scand J Gastroenterol 42: 221–227

    Article  Google Scholar 

  47. D'Ovidio V et al. (2006) Mucosal features and granulocyte-monocyte-apheresis in steroid-dependent/refractory ulcerative colitis. Dig Liver Dis 38: 389–394

    CAS  Article  Google Scholar 

  48. Hanai H et al. (2004) Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion 70: 36–44

    CAS  Article  Google Scholar 

  49. Fukuda Y et al. (2004) Adsorptive granulocyte and monocyte apheresis for refractory Crohn's disease: an open multicenter prospective study. J Gastroenterol 39: 1158–1164

    Article  Google Scholar 

  50. Giampaolo B et al. (2006) Treatment of active steroid-refractory inflammatory bowel diseases with granulocytapheresis: our experience with a prospective study. World J Gastroenterol 12: 2201–2204

    Article  Google Scholar 

  51. Suzuki Y et al. (2006) A retrospective search for predictors of clinical response to selective granulocyte and monocyte apheresis in patients with ulcerative colitis. Dig Dis Sci 51: 2031–2038

    Article  Google Scholar 

  52. Suzuki Y et al. (2004) Selective granulocyte and monocyte adsorptive apheresis as a first-line treatment for steroid naive patients with active ulcerative colitis: a prospective uncontrolled study. Dig Dis Sci 49: 565–571

    CAS  Article  Google Scholar 

  53. Sakuraba A et al. (2005) A multicenter randomized controlled trial between weekly and semiweekly treatment with granulocyte and monocyte adsorption apheresis for active ulcerative colitis. Gut 54 (Suppl VII): A57

    Google Scholar 

  54. Adacolumn [http://www.adacolumn.com/]

  55. Tanaka T et al. (2007) Adsorptive granulocytapheresis reduces mucosal level of neutrophils in patients with active ulcerative colitis and is most effective in steroid naïve patients. Gastroenterology 132 (Suppl S1): A347

    Google Scholar 

  56. Cohen RD (2005) Treating ulcerative colitis without medications—“Look Mom, No Drugs! Gastroenterology 128: 235–236

    Article  Google Scholar 

  57. Yamamoto T et al. (2007) Factors affecting clinical and endoscopic efficacies of selective leucocytapheresis for ulcerative colitis. Dig Liver Dis 39: 626–633

    CAS  Article  Google Scholar 

  58. Sawada K (2002) Therapeutic cytapheresis for ulcerative colitis. Medical Tribune Inc 133–149

  59. Sawada K 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: 1362–1369

    Article  Google Scholar 

  60. Sands BE et al. (2008) A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterology [10.1053/j.gastro.2008.04.023]

  61. Maiden L et al. (2008) Selective white cell apheresis reduces relapse rates in patients with IBD at significant risk of clinical relapse. Inflamm Bowel Dis [10.1002/ibd.20505]

  62. Kruis W et al. (2005) Open label trial of granulocyte apheresis suggests therapeutic efficacy in chronically active steroid refractory ulcerative colitis. World J Gastroenterol 11: 7001–7005

    Article  Google Scholar 

  63. Domenech E et al. (2004) Granulocyteaphaeresis in steroid-dependent inflammatory bowel disease: a prospective, open, pilot study. Aliment Pharmacol Ther 20: 1347–1352

    CAS  Article  Google Scholar 

  64. Suzuki Y (2002) Efficacy of granulocyte adsorption apheresis with G-1 column in the treatment of patients with active ulcerative colitis. Medical Tribune Inc 371–381

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Correspondence to Ingvar Bjarnason.

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During the past 2 years, Ingvar Bjarnason has been on the speakers' bureau for, and received grant/research support from, Otsuka. Fridrik T Sigurbjörnsson declared no competing interests.

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Sigurbjörnsson, F., Bjarnason, I. Leukocytapheresis for the treatment of IBD. Nat Rev Gastroenterol Hepatol 5, 509–516 (2008). https://doi.org/10.1038/ncpgasthep1209

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