Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Optimizing the safety of biologic therapy for IBD

Nature Reviews Gastroenterology & Hepatology volume 7, pages 93–101 (2010)Cite this article

Subjects

Abstract

The introduction of biologic therapy for the treatment of IBD has substantially changed its management. The safety concerns associated with biologic therapies include the increased risk of infection, autoimmunity, development of lymphoma and demyelinating disease, and the risk of worsening heart failure. There are several strategies for minimizing the risks associated with biologic therapies. Pretreatment strategies include taking a proper history from the patient, physical examination of the patient, screening for latent tuberculosis and ruling out sepsis. Vaccination of patients against vaccine preventable diseases is also recommended. During treatment, patients should be closely monitored and any symptoms that develop should be dealt with early. Education of physicians and patients is also important to allow the early detection of any adverse events.

Key Points

  • Biologic therapy has substantially altered the management of IBD in the past decade

  • Safety concerns associated with biologic therapies include the increased risk of infection, autoimmunity, development of lymphoma, demyelinating disease and worsening heart failure

  • Safety can be optimized by taking a proper patient history, physical examination of the patient, vaccinating against vaccine preventable diseases, screening for tuberculosis and ruling out sepsis

  • Regular follow-up during therapy with blood tests and physical examination also helps to optimize safety

  • Risks can be reduced further by promoting heightened awareness by both patients and physicians of the adverse effects associated with biologic therapy

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Fiocchi, C. Inflammatory bowel disease: aetiology and pathogenesis. Gastroenterology 115, 182–205 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. REMICADE® (infliximab) for injection. Prescribing information ( Malvern, P. C., Inc., 2008).

  3. HUMIRA® (adalimumab). Prescribing information (Abbott Laboratories, 2008).

  4. Cimzia® (certolizumab pegol). Prescribing information ( Smyrna, G. U., Inc., 2008).

  5. Tysabri® (natalizumab). Prescribing information (Elan Pharmaceuticals, 2008).

  6. Hanauer, S. B. et al. Maintenance infliximab for Crohn's disease: the ACCENT 1 randomised trial. Lancet 359, 1541–1549 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. Present, D. H. et al. Infliximab for the treatment of fistulas in patients with Crohn's disease. N. Engl. J. Med. 340, 1398–1405 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Sands, B. E. et al. Infliximab maintenance therapy for fistulizing Crohn's disease. N. Engl. J. Med. 350, 876–885 (2004).

    Article  CAS  PubMed  Google Scholar 

  9. Rutgeerts, P. et al. Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology 117, 761–769 (1999).

    Article  CAS  PubMed  Google Scholar 

  10. Rutgeerts, P. et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N. Engl. J. Med. 353, 2462–2476 (2005).

    Article  CAS  PubMed  Google Scholar 

  11. Colombel, J. F. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology 132, 52–65 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Hanauer, S. B. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology 130, 323–333 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Sandborn, W. J. et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial. Gut 56, 1232–1239 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Sandborn, W. J. et al. Certolizumab pegol for the treatment of Crohn's disease. N. Engl. J. Med. 357, 228–238 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Schreiber, S. et al. Maintenance therapy with certolizumab pegol for Crohn's disease. N. Engl. J. Med. 357, 239–250 (2007).

    Article  CAS  PubMed  Google Scholar 

  16. Schreiber, S. et al. A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease. Gastroenterology 129, 807–818 (2005).

    Article  CAS  PubMed  Google Scholar 

  17. Lichtenstein, G. et al. Serious infections and mortality in association with therapies for Crohn's disease: TREAT registry. Clin. Gastroenterol. Hepatol. 4, 621–630 (2006).

    Article  CAS  PubMed  Google Scholar 

  18. Viget, N., Vernier-Massouille, G., Salmon-Ceron, D., Yazdanpanah, Y. & Colombel, J. Opportunistic infections in patients with inflammatory bowel disease: prevention and diagnosis. Gut 57, 549–558 (2008).

    Article  CAS  PubMed  Google Scholar 

  19. Toruner, M. et al. Risk factors for opportunistic infections in patients with inflammatory bowel disease. Gastroenterology 134, 929–936 (2008).

    Article  PubMed  Google Scholar 

  20. Keane, J. et al. Tuberculosis associated with inflximab, a tumour necrosis factor alpha-neutralizing agent. N. Engl. J. Med. 345, 1098–1104 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Colbert, C., Chavarria, A. & Berkelhammer, C. Fulminant hepatic failure in chronic hepatitis B on withdrawal of corticosteroids, azathioprine and infliximab for Crohn's disease. Inflamm. Bowel Dis. 13, 1453–1454 (2007).

    Article  PubMed  Google Scholar 

  22. Esteve, M. et al. Chronic hepatitis B reactivation following infliximab therapy in Crohn's disease patients: need for primary prophylaxis. Gut 53, 1363–1365 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Caspersen, S. et al. Infliximab for inflammatory bowel disease in Denmark 1999–2005: clinical outcome and follow-up evaluation of malignancy and mortality. Clin. Gastroenterol. Hepatol. 6, 1212–1217 (2008).

    Article  PubMed  Google Scholar 

  24. Colombel, J. et al. The safety profile of inflximab in patients with Crohn's disease: the Mayo clinic experience in 500 patients. Gastroenterology 126, 19–31 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Chung, E. S. et al. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation 107, 3133–3140 (2003).

    Article  CAS  PubMed  Google Scholar 

  26. Ljung, T. et al. Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County. Gut 53, 849–853 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Siegel, C. A., Marden, S., Persing, S. M., Larson, R. J. & Sands, B. E. Risk of lymphoma associated with combination anti-tumor necrosis factor and immunomodulator therapy for the treatment of Crohn's disease: a meta-analysis. Clin. Gastroenterol. Hepatol. 7, 874–881 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sands, B. E. et al. Guidelines for immunizations in patients with inflammatory bowel disease. Inflamm. Bowel Dis. 10, 677–692 (2004).

    Article  PubMed  Google Scholar 

  29. Melmed, G. Y. et al. Patients with inflammatory bowel disease are at risk for vaccine-preventable illnesses. Am. J. Gastroenterol. 101, 1834–1840 (2006).

    Article  PubMed  Google Scholar 

  30. Mamula, P. et al. Immune response to influenza vaccine in pediatric patients with inflammatory bowel disease. Clin. Gastroenterol. Hepatol. 5, 851–856 (2007).

    Article  PubMed  Google Scholar 

  31. Colombel, J. F. et al. Adalimumab safety in global clinical trials of patients with Crohn's disease. Inflamm. Bowel Dis. 15, 1308–1319 (2009).

    Article  PubMed  Google Scholar 

  32. Sandborn, W. J. & Targan, S. R. Biologic therapy of inflammatory bowel disease. Gastroenterology 122, 1592–1608 (2002).

    Article  CAS  PubMed  Google Scholar 

  33. Lichtenstein, G. et al. Safety of infliximab and other Crohn's disease therapies: Treat Registry Data with 24,575 patient-years of follow up [abstract]. Am. J. Gastroenterol. 108 (Suppl. S1), a1116 (2008).

    Google Scholar 

  34. D'Haens, G. et al. Corticosteroids pose an increased risk of serious infection: an interim safety analysis of the ENCORE registry [abstract]. Gastroenterology 134 (Suppl. DDW), a946 (2008).

    Google Scholar 

  35. Rahier, J. F. et al. European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J. Crohn's Colitis 3, 47–91 (2009).

    Article  CAS  Google Scholar 

  36. Fidder, H. et al. Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-center cohort study. Gut 58, 501–508 (2009).

    Article  CAS  PubMed  Google Scholar 

  37. Rutgeerts, P., Van Assche, G. & Vermeire, S. Optimizing anti-TNF treatment in inflammatory bowel disease. Gastroenterology 126, 1593–1610 (2004).

    Article  CAS  PubMed  Google Scholar 

  38. Mow, W. S. et al. High incidence of anergy in inflammatory bowel disease patients limits the usefulness of PPD screening before infliximab therapy. Clin. Gastroenterol. Hepatol. 2, 309–313 (2004).

    Article  PubMed  Google Scholar 

  39. Pai, M., Zwerling, A. & Menzies, D. Systematic review: T-cell-based assays for the diagnosis of latent tuberculosis infection: an update. Ann. Intern. Med. 149, 177–184 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lavagna, A. et al. Infliximab and the risk of latent viruses reactivation in active Crohn's disease. Inflamm. Bowel Dis. 13, 896–902 (2007).

    Article  PubMed  Google Scholar 

  41. D'Ovidio, V. et al. Cytomegalovirus infection in inflammatory bowel disease patients undergoing anti-TNFalpha therapy. J. Clin. Virol. 43, 180–183 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Melmed, G. Y. Vaccination strategies for patients with inflammatory bowel disease on immunomodulators and biologics. Inflamm. Bowel Dis. 15, 1410–1416 (2009).

    Article  PubMed  Google Scholar 

  43. [No authors listed] Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 46 (RR-6), 1–26 (1998).

  44. [No authors listed] Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm. Rep. 46 (RR-8), 1–24 (1997).

  45. D'Haens, G. Risks and benefits of biologic therapy for inflammatory bowel diseases. Gut 56, 725–732 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Vermeire, S. et al. Autoimmunity associated with anti-tumor necrosis factor alpha treatment in Crohn's disease: a prospective cohort study. Gastroenterology 125, 32–39 (2003).

    Article  CAS  PubMed  Google Scholar 

  47. Munkholm, P., Langholz, E., Davidsen, M. & Binder, V. Intestinal cancer risk and mortality in patients with Crohn's disease. Gastroenterology 105, 1716–1723 (1993).

    Article  CAS  PubMed  Google Scholar 

  48. Peyrin-Biroulet, L. et al. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin. Gastroenterol. Hepatol. 6, 644–653 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Biancone, L., Calabrese, E., Petruzziello, C. & Pallone, F. Treatment with biologic therapies and the risk of cancer in patients with IBD. Nat. Clin. Pract. Gastroenterol. Hepatol. 4, 78–91 (2007).

    Article  CAS  PubMed  Google Scholar 

  50. Biancone, L. et al. Infliximab and newly diagnosed neoplasia in Crohn's disease: a multicentre matched pair study. Gut 55, 228–233 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Lewis, J. D. et al. Inflammatory bowel disease is not associated with an increased risk of lymphoma. Gastroenterology 121, 1080–1087 (2001).

    Article  CAS  PubMed  Google Scholar 

  52. Askling, J. et al. Risk of haematopoietic cancer in patients with inflammatory bowel disease. Gut 54, 617–622 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bernstein, C. N., Blanchard, J. F., Kleiwer, E. & Wajda, A. Cancer risk in patients with inflammatory bowel disease: a population-based study. Cancer 91, 854–862 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Bongartz, T. et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infection and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295, 2275–2285 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Beaugerie, L. et al. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 374, 1617–1625 (2009).

    Article  CAS  PubMed  Google Scholar 

  56. Rosh, J. R., Gross, T., Mamula, P., Griffiths, A. & Hyams, J. Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn's disease: a cautionary tale? Inflamm. Bowel Dis. 13, 1024–1030 (2007).

    Article  PubMed  Google Scholar 

  57. Shale, M., Kanfer, E., Panaccione, R. & Ghosh, S. Hepatosplenic T cell lymphoma in inflammatory bowel disease. Gut 57, 1639–1641 (2008).

    Article  PubMed  Google Scholar 

  58. Kane, S., Khatibi, B. & Reddy, D. Use of immunosuppressant results in higher incidence of abnormal PAP smears in women with inflammatory bowel disease. Gastroenterology 130 (Suppl.), A2 (2006).

    Google Scholar 

  59. Singh, H. et al. Risk of cervical abnormalities in women with inflammatory bowel disease: a population-based nested case–control study. Gastroenterology 136, 451–458 (2009).

    Article  PubMed  Google Scholar 

  60. Lees, C. W. Lack of association between cervical dysplasia and IBD: a large case–control study. Inflamm. Bowel Dis. 15, 1621–1629 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Kane, S. Abnormal Pap smears in inflammatory bowel disease. Inflamm. Bowel Dis. 14, 1158–1160 (2008).

    Article  PubMed  Google Scholar 

  62. Ghosh, S. alpha 4 integrin blockage in inflammatory bowel disease. Ann. Rheum. Dis. 62 (Suppl. II), ii70–ii72 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Baker, D. E. Natalizumab: overview of its pharmacology and safety. Rev. Gastroenterol. Disord. 7, 38–46 (2007).

    PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  65. Kleinschmidt-DeMasters, B. K. & Tyler, K. L. Progressive multifocal leukoencephalopathy complicating treatment with natalizumab and interferon beta-1a for multiple sclerosis. N. Engl. J. Med. 353, 369–374 (2005).

    Article  CAS  PubMed  Google Scholar 

  66. Langer-Gould, A., Atlas, S. W., Green, A. J., Bollen, A. W. & Pelletier, D. Progressive multifocal leukoencephalopathy in a patient treated with natalizumab. N. Engl. J. Med. 353, 375–381 (2005).

    Article  CAS  PubMed  Google Scholar 

  67. Food and Drug Administration. Information on Natalizumab (marketed as Tysabri) Food and Drug Administration [online], (2009).

Download references

Acknowledgements

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. Inflammatory Bowel Disease Clinic, University of Calgary, Room 6D30, Teaching, Research, and Wellness (TRW) Building, 3280 Hospital Drive NW, Calgary, AB T2N 4N1, Canada

    Shanika de Silva, Shane Devlin & Remo Panaccione

Authors
  1. Shanika de Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shane Devlin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Remo Panaccione
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Remo Panaccione.

Ethics declarations

Competing interests

The other authors, the Journal Editor N. Wood and the CME questions author D. Lie declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Silva, S., Devlin, S. & Panaccione, R. Optimizing the safety of biologic therapy for IBD. Nat Rev Gastroenterol Hepatol 7, 93–101 (2010). https://doi.org/10.1038/nrgastro.2009.221

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2009.221

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing