Infliximab in Crohn disease
- Richard P MacDermott, MD
Richard P MacDermott, MD
- Emeritus Professor of Medicine, Division of Gastroenterology
- The Albany Medical College
- Gary R Lichtenstein, MD
Gary R Lichtenstein, MD
- Professor of Medicine
- Director, Center for Inflammatory Bowel Diseases
- University of Pennsylvania School of Medicine
Infliximab is a chimeric IgG 1 monoclonal antibody comprised of 75 percent human and 25 percent murine sequences, which has a high specificity for and affinity to tumor necrosis factor (TNF)-alpha. Infliximab is available for treatment of patients with moderately to severely active Crohn disease and patients with fistulizing Crohn disease, who have had an inadequate response to conventional therapy.
TNF-alpha has several biologic activities that may be directly related to the pathogenesis of inflammatory bowel disease and there is increasing evidence suggesting a central role for TNF-alpha in Crohn disease . As an example, stool TNF-alpha levels are elevated in patients with Crohn disease and correlate with disease activity . (See "Immune and microbial mechanisms in the pathogenesis of inflammatory bowel disease".)
Infliximab neutralizes the biologic activity of TNF-alpha by inhibiting binding to its receptors. However, infliximab's mechanism of action most likely involves the destruction of activated effector cells through apoptosis and/or other mechanisms [3-7]. Treatment of patients with infliximab markedly decreases endoscopic and histologic disease activity in Crohn colitis [8,9].
The role of infliximab in Crohn disease will be reviewed here. Conventional, alternative, and other types of immunomodulator therapy for Crohn disease are discussed separately (see appropriate topic reviews). The American Gastroenterological Association (AGA) guideline for glucocorticoids, immunomodulators, and infliximab in inflammatory bowel disease , as well as other AGA guidelines, can be accessed through the AGA website. In addition, the American College of Gastroenterology (ACG) has issued practice guidelines that can be accessed through the ACG website.
INDUCTION OF REMISSION IN PATIENTS WITH ACTIVE CROHN DISEASE
Multiple studies have evaluated the efficacy of infliximab in patients with active, non-fistulizing Crohn disease. Several centers have also published their clinical experience with infliximab, which provides further insight into the effectiveness of infliximab outside of the clinical trials setting. A meta-analysis found that patients treated with infliximab were less likely to fail to achieve remission than patients treated with placebo (RR 0.68) . (See 'Experience in clinical practice' below.)
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- INDUCTION OF REMISSION IN PATIENTS WITH ACTIVE CROHN DISEASE
- INDUCTION OF REMISSION IN FISTULIZING DISEASE
- MAINTENANCE OF RESPONSE AND REMISSION
- Patients without fistulizing disease
- - Initial clinical response
- - Maintenance
- - Steroid tapering
- - Quality of life
- - Toxicity
- - Limitations
- Use of immunosuppressive agents in combination with infliximab
- Switching from infliximab to an alternative anti-TNF agent
- Patients with fistulizing disease
- - Rectovaginal fistulas
- EXTRAINTESTINAL MANIFESTATIONS
- EXPERIENCE IN CLINICAL PRACTICE
- Predictors of response
- USE IN THE SETTING OF INTESTINAL STRICTURES
- PEDIATRIC EXPERIENCE
- ADVERSE EVENTS
- ADALIMUMAB VERSUS INFLIXIMAB VERSUS CERTOLIZUMAB
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS