Optimizing anti-tumor necrosis factor strategies in inflammatory bowel disease
- William J. Sandborn MD
- … show all 1 hide
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
The introduction of infliximab, a mouse/human chimeric monoclonal antibody to tumor necrosis factor (TNF), is an important advance in the treatment of Crohn’s disease. Infliximab is effective for induction and maintenance of remission in patients with inflammatory luminal and fistulizing disease. The development of human antichimeric antibodies (HACAs) has led to infusion reactions and loss of efficacy in patients treated with infliximab. Strategies to reduce the frequency of HACA formation include induction of immunologic tolerance with a three-dose regimen at 0, 2, and 6 weeks followed by systematic maintenance dosing every 8 weeks; concomitant immunosuppressive therapy with azathioprine, 6-mercaptopurine, or methotrexate; and premedication with intravenous corticosteroids. Humanized or fully human anti-TNF biotechnologic agents, including CDP571, CDP870, etanercept, adalimumab, and onercept, are theoretically less immunogenic than the chimeric antibody infliximab. Etanercept is not effective for Crohn’s disease. CDP571 is not effective in unselected patients with active Crohn’s disease, but it may be effective in patients with elevated C-reactive protein. The efficacy of CDP870, adalimumab, and onercept is under investigation. The different mechanisms of action of these anti-TNF agents may account for their variable efficacy. Their benefits, however, must be considered in the context of their risks, including infusion reaction; delayed hypersensitivitylike reaction; new onset of autoimmunity, with rare cases of drug-induced lupus and new-onset demyelination; and the potential for rare but serious infections.
- Lugering A, Schmidt M, Lugering N, et al.: Infliximab induces apoptosis in monocytes from patients with chronic active Crohn’s disease by using a caspase-dependent pathway. Gastroenterology 2001, 121:1145–57. CrossRef
- ten Hove T, van Montfrans C, Peppelenbosch MP, van Deventer SJ: Infliximab treatment induces apoptosis of lamina propria T lymphocytes in Crohn’s disease. Gut 2002, 50:206–11. CrossRef
- van den Brande JMH, Braat H, van den Brink GR, et al.: Infliximab but not etanercept induces apopotosis in lamina propria T-lymphocytes from patients with Crohn’s disease. Gastroenterology 2003, 124:1774–1785. CrossRef
- 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. Landmark trial demonstrating the efficacy of infliximab for active Crohn’s disease. CrossRef
- Hanauer SB, Feagan BG, Lichtenstein GR, et al.: Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002, 359:1541–1549. Landmark trial demonstrating the efficacy of infliximab as maintenance therapy for Crohn’s disease. CrossRef
- 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. Landmark trial demonstrating the efficacy of infliximab for closing actively draining fistulae in patients with Crohn’s disease. CrossRef
- Sands B, Van Deventer S, Bernstein C, et al.: Long-term treament of fistulizing Crohn’s disease: response to infliximab in the ACCENT II trial through 54 weeks. Gastroenterology 2002, 122:A81.
- SandbornWJ, Hanauer SB, Katz S, et al.: Etanercept for active Crohn’s disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 2001, 121:1088–1094. Important study demonstrating that etanercept is not effective for the treatment of active Crohn’s disease. CrossRef
- 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. CrossRef
- 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. CrossRef
- Sandborn W, Feagan B, Radford-Smith G, et al.: Randomized, placebo-controlled trial of CDP571, a humanized monoclonal antibody to TNF-a, in patients with moderate to severe Crohn’s disease [abstract]. Gastroenterology 2003, 124:A-61.
- Feagan BG, Sandborn WJ, Baker J, et al.: A randomized, double-blind, placebo-controlled, multi-center trial of the engineered human antibody to TNF (CDP571) for steroid sparing and maintenance of remission in patients with steroiddependent Crohn’s disease [abstract]. Gastroenterology 2000, 118:A655. CrossRef
- Celltech announces results from CDP 571 studies in Crohn’s disease. http://www.inpharma.com/news.
- Schreiber S, Rutgeerts P, Fedorak R, et al., and the CDP870 Crohn’s Disease Study Group: CDP870, a humanized anti-TNF antibody fragment, induces clinical response with remission in patients with active Crohn’s disease (CD) [abstract]. Gastroenterology 2003, 124:A-61. CrossRef
- Rutgeerts P, Lemmens L, Van Assche G, et al.: Treatment of active Crohn’s disease with onercept (recombinant human soluble p55 tumour necrosis factor receptor): results of a randomized, open-label, pilot study. Aliment Pharmacol Ther 2003, 17:185–92. CrossRef
- Mayer L, Han C, Bala M, et al.: Three dose induction regimen of infliximab (Remicade) is superior to a single dose in patients with Crohn’s disease. Am J Gastroenterol 2001, 96:S303. CrossRef
- 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. CrossRef
- Cheifetz A, Smedley M, Martin S, et al.: The incidence and management of infusion reactions to infliximab: a large center experience. Am J Gastroenerol 2003, 98:1315–1324. CrossRef
- Hanauer S, Rutgeerts P, Targan S, et al.: Delayed hypersensitivity to infliximab (Remicade) re-infusion after a 2–4 year interval without treatment [abstract]. Gastroenterology 1999, 116:A731.
- Mohan N, Edwards ET, Cupps TR, et al.: Demyelination occurring during anti-tumor necrosis factor alpha therapy for inflammatory arthritides. Arthritis Rheum 2001, 44:2862–2869. CrossRef
- Brown SL, Greene MH, Gershon SK, et al.: Tumor necrosis factor antagonist therapy and lymphoma development: twentysix cases reported to the Food and Drug Administration. Arthritis Rheum 2002, 46:3151–3158. CrossRef
- 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.
- Remicade (infliximab) for IV injection [package insert]. Malvern, PA: Centocor; 2002.
- Hanauer SB. Review article: safety of infliximab in clinical trials. Aliment Pharmacol Ther 1999, 13(Suppl 4):16–22. CrossRef
- Schaible TF: Long term safety of infliximab. Can J Gastroenterol 2000, 14(Suppl C):29C-32C.
- Sandborn WJ, Hanauer SB: Infliximab in the treatment of Crohn’s disease: a user’s guide for clinicians. Am J Gastroenterol 2002, 97:2962–2972. CrossRef
- 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. CrossRef
- Lee JH, Slifman NR, Gershon SK, et al.: Life-threatening histoplasmosis complicating immunotherapy with tumor necrosis factor alpha antagonists infliximab and etanercept. Arthritis Rheum 2002, 46:2565–2570. CrossRef
- Maini RN, Breedveld FC, Kalden JR, et al.: Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis. Arthritis Rheum 1998, 41:1552–1563. CrossRef
- LoBuglio AF, Wheeler RH, Trang J, et al.: Mouse/human chimeric monoclonal antibody in man: kinetics and immune response. Proc Natl Acad Sci U S A 1989, 86:4220–4224. CrossRef
- Rutgeerts P, D’Haens G, Targan S, et al.: Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn’s disease. Gastroenterology 1999, 117:761–769. CrossRef
- Remicade (infliximab) for IV injection [prescribing information]. Malvern, PA: Centocor; 2002.
- Sandborn WJ: Preventing antibodies to infliximab in patients with Crohn’s disease: optimize not immunize. Gastroenterology 2003, 124:1140–1145.
- Baert F, Noman M, Vermeire S, et al.: Influence of immunogenicity on the long-term efficacy of infliximab in Crohn’s disease. N Engl J Med 2003, 348:601–608. Landmark study demonstrating the immunogenicity of episodically administered infliximab in patients with Crohn’s disease. CrossRef
- Farrell RJ, Alsahli M, Jeen YT, et al.: Intravenous hydrocortisone premedication reduces antibodies to infliximab in Crohn’s disease: a randomized controlled trial. Gastroenterology 2003, 124:917–924. Important study demonstrating the immunogenicity of infliximab and the protective effect of pretreatment with corticosteroids. CrossRef
- Hanauer S, Present D, Targan SR, et al.: CDP571, a humanized monoclonal antibody to TNF-a, is well tolerated in Crohn’s disease patients with previous hypersensitivity to infliximab [abstract]. Gastroenterology 2003, 124:A-517. CrossRef
- Winter T, Wright J, Ghosh S, et al.: Intravenous CDP870, a humanized anti-TNF antibody fragment, in patients with active Crohn’s disease: an exploratory study [abstract]. Gastroenterology 2003, 124:A-377. CrossRef
- Optimizing anti-tumor necrosis factor strategies in inflammatory bowel disease
Current Gastroenterology Reports
Volume 5, Issue 6 , pp 501-505
- Cover Date
- Print ISSN
- Online ISSN
- Current Medicine Group
- Additional Links
- Author Affiliations
- 1. Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street SW, 55905, Rochester, MN, USA