Abstract
Traditional medications for inflammatory bowel disease are small molecule drugs, most of which were developed for use in other diseases before being found to be efficacious for the treatment of ulcerative colitis or Crohn’s disease. Recently, several exciting alternative approaches to the medical treatment of inflammatory bowel disease have been developed. These include biologic, probiotic, and apheresis therapies that offer certain advantages over traditional drug therapy for inflammatory bowel disease. The purpose of this review is to assess the current state of knowledge about novel biologic, probiotic, and apheresis therapies and to analyze how best to incorporate these therapies into evolving management paradigms of inflammatory bowel disease.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References and Recommended Reading
Sandborn WJ, Hanauer SB, Katz S, et al.: Etanercept for active Crohn’s disease: a randomized, double-blind, placebocontrolled trial. Gastroenterology 2001, 121:1088–1094.
Rutgeerts P, Fedorak RN, Rachmilevich D, et al.: Onercept (recombinant human p55 tumour necrosis factor receptor) treatment in patients with active Crohn’s disease: randomized, placebo-controlled, dose-finding phase II study. Gut 2004, 53(Suppl VI):A47.
Hanauer SB, Feagan BG, Lichtenstein GR, et al.: Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002, 359:1541–1549. A landmark study that established the benefit of long-term therapy with infliximab in luminal Crohn’s disease.
Targan SR, Hanauer SB, van Deventer SJ, et al.: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 1997, 337:1029–1035.
Hanauer S, Lukás M, MacIntosh D, et al.: A randomized, doubleblind, placebo-controlled trial of the human anti-TNF-a monoclonal antibody adalimumab for the induction of remission in patients with moderate to severely active Crohn’s disease. Gastroenterology 2004, 127:332.
Rutgeerts P, Colombel J, Enns R, et al.: Subanalyses from a phase 3 study on the evaluation of natalizumab in active Crohn’s disease therapy-I (ENACT-1). Gut 2003, 52(Suppl):A239.
Sandborn WJ, Hanauer SB, Lukas M, et al.: Maintenance of remission over 1 year in patients with active Crohn’s disease treated with adalimumab: results of a blinded placebocontrolled trial. Am J Gastroenterol 2005, in press.
Present DH, Rutgeerts P, Targan S, et al.: Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med 1999, 340:1398–1405.
Sands BE, Anderson FH, Bernstein CN, et al.: Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004, 350:876–885. A landmark study that established the benefit of long-term therapy with infliximab in fistulizing Crohn’s disease.
Ricart E, Panaccione R, Loftus EV, et al.: Successful management of Crohn’s disease of the ileoanal pouch with infliximab. Gastroenterology 1999, 117:429–432.
Colombel JF, Ricart E, Loftus EV Jr, et al.: Management of Crohn’s disease of the ileoanal pouch with infliximab. Am J Gastroenterol 2003, 98:2239–2244.
van der Heijde D, Dijkmans B, Geusens P, et al.: Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Arthritis Rheum 2005, 52:582–591.
Brooklyn T, Shetty A, Bowden J, et al.: Infliximab for the treatment of pyoderma gangrenosum: a randomised, doubleblind placebo-controlled trial. Gastroenterology 2005, 128:A26.
Sandborn WJ, Feagan BG, Hanauer SB, et al.: An engineered human antibody to TNF (CDP571) for active Crohn’s disease: a randomized double-blind placebo-controlled trial. Gastroenterology 2001, 120:1330–1338.
Feagan BG, Sandborn WJ, Baker JP, et al.: A randomized, doubleblind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn’s disease. Aliment Pharmacol Ther 2005, 21:373–384.
Sandborn WJ, Feagan BG, Radford-Smith G, et al.: CDP571, a humanised monoclonal antibody to tumour necrosis factor alpha, for moderate to severe Crohn’s disease: a randomised, double blind, placebo controlled trial. Gut 2004, 53:1485–1493.
Stack WA, Mann SD, Roy AJ, et al.: Randomised controlled trial of CDP571 antibody to tumour necrosis factor-alpha in Crohn’s disease. Lancet 1997, 349:521–524.
Schreiber S, Rutgeerts P, Fedorak RN, et al.: A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn’s disease. Gastroenterology 2005, 129:807–818.
Sandborn WJ, Rachmilewitz D, Hanauer SB, et al.: Infliximab induction and maintenance therapy for ulcerative colitis: the ACT2 trial. Gastroenterology 2005, 128:A104-A105.
Rutgeerts P, Feagan BG, Olson A, et al.: A randomized placebocontrolled trial of infliximab therapy for active ulcerative colitis: ACT 1 trial. Gastroenterology 2005, 128:A105.
Keane J, Gershon S, Wise RP, et al.: Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 2001, 345:1098–1104. This paper established the potential of in fliximab to cause reactivation of latent tuberculosis, a very serious adverse effect of this agent.
Colombel JF, Loftus EV Jr, Tremaine WJ, et al.: The safety profile of infliximab in patients with Crohn’s disease: the Mayo clinic experience in 500 patients. Gastroenterology 2004, 126:19–31.
Velayos FS, Sandborn WJ: Pneumocystis carinii pneumonia during maintenance anti-tumor necrosis factor-alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 2004, 10:657–660.
Riegert-Johnson DL, Godfrey JA, Myers JL, et al.: Delayed hypersensitivity reaction and acute respiratory distress syndrome following in fliximab infusion. Inflamm Bowel Dis 2002, 8:186–191.
Kwon HJ, Cote TR, Cuffe MS, et al.: Case reports of heart failure after therapy with a tumor necrosis factor antagonist. Ann Intern Med 2003, 138:807–811.
Thomas CW Jr, Weinshenker BG, Sandborn WJ: Demyelination during anti-tumor necrosis factor alpha therapy with infliximab for Crohn’s disease. Inflamm Bowel Dis 2004, 10:28–31.
Vermeire S, Noman M, Van Assche G, et al.: Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn’s disease: a prospective cohort study. Gastroenterology 2003, 125:32–39.
Prescribing information for Humira (adalimumab). Package insert;. Abbot Park, IL: Abbott Labs; 2004.
Schreiber S, Rutgeerts P, Fedorak RN, et al.: CDP870, a humanized anti-TNF antibody fragment, induces clinical response with remission in patients with active Crohn’s disease. Gastroenterology 2003, 124:A61.
Cosnes J, Nion-Larmurier I, Beaugerie L, et al.: Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery. Gut 2005, 54:237–241.
Lemann M, Colombel JF, Duclos B, et al.: Infliximab in steroid dependent Crohn’s disease patients treated with azathioprine or 6-mercaptopurine: a randomized double-blind placebo controlled trial. Gastroenterology 2003, 125:3.
Hommes D, Baert F, Van Assche G, et al.: Management of recent onset Crohn’s disease: a controlled randomized trial comparing step-up and top-down therapy. Gastroenterology 2005, 129:371.
Baert F, Noman M, Vermeire S, et al.: Influence of immunogenicity on the long-term efficacy of in fliximab in Crohn’s disease. N Engl J Med 2003, 348:601–608. This important study demonstrated an association between the presence of anti-infliximab antibodies and the loss of efficacy of this agent.
Sandborn WJ: Preventing antibodies to in fliximab in patients with Crohn’s disease: optimize not immunize. Gastroenterology 2003, 124:1140–1145.
Farrell RJ, Alsahli M, Jeen YT, et al.: Intravenous hydrocortisone premedication reduces antibodies to in fliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 2003, 124:917–924.
Hanauer SB, Wagner CL, Bala M, et al.: Incidence and importance of antibody responses to in fliximab after maintenance or episodic treatment in Crohn’s disease. Clin Gastroenterol Hepatol 2004, 2:542–553.
Sandborn W, Colombel JF, Enns R, et al.: Efficacy, safety, and tolerability of natalizumab in maintaining clinical response and remission in Crohn’s disease (ENACT-2). Am J Gastroenterol 2004, 99:S255-S256.
Ghosh S, Goldin E, Gordon FH, et al.: Natalizumab for active Crohn’s disease. N Engl J Med 2003, 348:24–32.
Sandborn WJ, Colombel JF, Enns R, et al.: Natalizumab induction and maintenance therapy for Crohn’s disease: the ENACT-1 and ENACT-2 trials. N Engl J Med 2005, in press. Results of the largest clinical trials conducted in inflammatory bowel disease to date have established the short- and long-term benefit of anti-integrin therapy for Crohn’s disease.
Van Assche G, Van Ranst M, Sciot R, et al.: Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn’s disease. N Engl J Med 2005, 353:362–368.
Kleinschmidt-Demasters BK, Tyler KL: Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N Engl J Med 2005, 353:369–374.
Langer-Gould A, Atlas SW, Bollen AW, Pelletier D: Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N Engl J Med 2005, 353:375–381.
Feagan BG, Greenberg GR, Wild G, et al.: Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 2005, 352:2499–2507. A selective inhibitor of leukocyte trafficking into the gut was found efficacious for ulcerative colitis.
Targan S, Salzberg BA, Mayer L, et al.: A phase I-II study: Multiple dose levels of visilizumab are well tolerated and produce rapid and sustained improvement in ulcerative colitis patients refractory to treatment with IV steroids. Gastroenterology 2005, 128:A493.
Creed TJ, Norman MR, Probert CS, et al.: Basiliximab (anti-CD25) in combination with steroids may be an effective new treatment for steroid-resistant ulcerative colitis. Aliment Pharmacol Ther 2003, 18:65–75.
Van Assche G, Dalle I, Noman M, et al.: A pilot study on the use of the humanized anti-interleukin-2 receptor antibody daclizumab in active ulcerative colitis. Am J Gastroenterol 2003, 98:369–376.
Hommes D, Mikhajlova T, Stoinov S, et al.: Fontolizumab(HuZAFTM), a humanized anti-IFN-gamma antibody, has clinical activity and excellent tolerability in moderate to severe Crohn’s disease (CD). Gastroenterology 2004, 127:332.
Ito H, Takazoe M, Fukuda Y, et al.: A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn’s disease. Gastroenterology 2004, 126:989–996; discussion 947.
Mannon PJ, Fuss IJ, Mayer L, et al.: Anti-interleukin-12 antibody for active Crohn’s disease. N Engl J Med 2004, 351:2069–2079. This clinical trial established the therapeutic benefit in Crohn’s disease of selectively inhibiting a central T-helper type I cytokine, IL-12.
Shanahan F: Physiological basis for novel drug therapies used to treat the inflammatory bowel diseases I: pathophysiological basis and prospects for probiotic therapy in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2005, 288:G417–421.
Gionchetti P, Rizzello F, Venturi A, et al.: Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 2000, 119:305–309.
Gionchetti P, Rizzello F, Helwig U, et al.: Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebocontrolled trial. Gastroenterology 2003, 124:1202–1209.
Mimura T, Rizzello F, Helwig U, et al.: Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 2004, 53:108–114.
Guslandi M, Mezzi G, Sorghi M, Testoni PA: Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 2000, 45:1462–1464.
Kruis W, Fric P, Pokrotnieks J, et al.: Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut 2004, 53:1617–1623.
Kuisma J, Mentula S, Jarvinen H, et al.: Effect of Lactobacillus rhamnosus GG on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther 2003, 17:509–515.
Rembacken BJ, Snelling AM, Hawkey PM, et al.: Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 1999, 354:635–639.
Steidler L, Hans W, Schotte L, et al.: Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 2000, 289:1352–1355.
Naganuma M, Funakoshi S, Sakuraba A, et al.: Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis 2004, 10:251–257.
Shimoyama T, Sawada K, Hiwatashi N, et al.: Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apheresis 2001, 16:1–9.
Fukuda Y, Matsui T, Suzuki Y, et al.: Adsorptive granulocyte and monocyte apheresis for refractory Crohn’s disease: an open multicenter prospective study. J Gastroenterol 2004, 39:1158–1164.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Egan, L.J., Sandborn, W.J. Positioning novel biologic, probiotic, and apheresis therapies for crohn’s disease and ulcerative colitis. Curr Gastroenterol Rep 7, 485–491 (2005). https://doi.org/10.1007/s11894-005-0080-3
Issue Date:
DOI: https://doi.org/10.1007/s11894-005-0080-3