An overview of a presentation by Professor Stephen Hanauer, Joseph B Kirsner Professor of Medicine, University of Chicago, USA, at the Raising Expectations in Gastroenterology symposium, 2010.

Long-term therapy for inflammatory bowel disease (IBD) should be regarded as a sequential process in which remission is induced and then maintained. The choice of induction agent is typically based on the severity of presenting symptoms. Maintenance can be achieved with continuation of aminosalicylates alone for some patients, while others will require longer-term treatment with a thiopurine, methotrexate or anti-TNF agent. Corticosteroid use for symptom control is often seen as a 'tipping point', indicating a need to intensify treatment.

The impact of treatment on Crohn's disease depends on the degree of structural damage that has occurred and velocity of progression of disease. Risk factors for progressive Crohn's disease include smoking, the presence of deep ulceration and younger age at onset.

Shifting goals in IBD management

Current practice involves taking a 'bottoms up' approach to therapy and conservative use of immunomodulators. In the future, it is expected that healthcare professionals will utilise immunomodulators at earlier stages of the disease course. Goals for IBD management are expected to shift to include mucosal healing and disease modification, as well as symptom control, better quality of life, minimisation of drug toxicity and disease complications, and optimisation of surgical outcomes.

The development of predictive biomarkers of disease risk, including molecular and genetic markers, could help predict the course of disease and its response to therapy. Ultimately research must focus on identifying the cause of disease and eliminating (or improving tolerance to) environmental factors.

Treatment with infliximab post-ileal resection

A study of Crohn's disease patients that have undergone ileal resection found infliximab to be effective at preventing one year endoscopic and histological postoperative recurrence of disease – the proportion of patients with endoscopic recurrence at one year (the primary outcome) was significantly lower in the infliximab group vs placebo group (9.1% vs 84.6%, p=0.0006). Adverse events were similar in the infliximab and placebo groups, and none occurred in the immediate postoperative period.1

Assessing loss of response to a biologic

The first step in assessing IBD patients who have lost their response to a biologic therapy is to determine whether active inflammation is present. If present, immunogenicity may be a cause and switching to another biologic may be effective. If there is no inflammation, switching to another biologic is unlikely to help.

If the patient has been treated with infliximab, an alternative anti-TNF agent may be effective in those with infliximab antibodies. If there are no antibodies and low infliximab blood levels, a shorter interval between infusions or a higher dose can assist. If there are no antibodies and blood levels appear adequate, then switching to a biologic with a different mechanism of action, rather than to another anti-TNF agent, is recommended.

Summary

  • Long-term therapy for IBD should be regarded as a sequential process in which remission is induced and then maintained
  • The impact of treatment depends on the degree of structural damage and velocity of progression of disease
  • The goals of treatment and research are expected to shift in the future
  • Infliximab may prevent Crohn's disease recurrence after ileal resection
  • There are a number of approaches to managing loss of response to biologic therapy

Please note, the views expressed in this article are not necessarily those of the sponsor.

Reference

  1. Regueiro M et al. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology 2009; 136: 441–450.

REMICADE® (infliximab) PBS INFORMATION. Crohn's disease: This is listed as a Section 100 item.

Acute Severe Ulcerative Colitis: This is listed as a Section 100 item [Public Hospital Authority Required (Streamlined); Private Hospital Authority Required]. Please refer to PBS Schedule for full authority information.

Chronic Refractory Ulcerative Colitis: Not listed on the PBS.

Please refer to Product Information before prescribing. Full product Information is available here. Further information is available on request from Janssen-Cilag.

®Registered Trademark of Janssen-Cilag Pty Ltd. ABN 47 000 129 975. 1–5 Khartoum Road, Macquarie Park NSW 2113. Tel: 1800 226 334. AU-REM0178. McCann Health REM0165. Date prepared: April 2014.

PBS information: This product is listed as a Section 100 item for Crohn’s disease and ulcerative colitis. Refer to PBS Schedule for full authority information.

Please refer to Product Information before prescribing. Full product Information is available here. Further information is available on request from Janssen-Cilag.

®Registered Trademark of Janssen-Cilag Pty Ltd. ABN 47 000 129 975. 1–5 Khartoum Road, Macquarie Park NSW 2113. Tel: 1800 226 334. AU-REM0178. McCann Health REM0165. Date prepared: April 2014. Updated: September 2015.