Natalizumab for treatment of Crohn disease in adults
- Joshua R Korzenik, MD
Joshua R Korzenik, MD
- AGA Peer Reviewer
- Assistant Professor of Medicine
- Harvard Medical School
Natalizumab is a humanized monoclonal antibody to alpha-4 integrin that was initially approved for treatment of multiple sclerosis and more recently for Crohn disease [1,2]. It is generally reserved for patients with moderate to severe Crohn disease that is refractory to other forms of medical therapy.
This topic will review the use of natalizumab in the treatment of Crohn disease. Other approaches to the medical management of Crohn disease are discussed elsewhere. (See "Overview of the medical management of mild to moderate Crohn disease in adults" and "Infliximab in Crohn disease" and "Adalimumab for treatment of Crohn disease in adults" and "Certolizumab pegol for treatment of Crohn disease in adults" and "Budesonide in the treatment of inflammatory bowel disease in adults" and "Antibiotics for treatment of inflammatory bowel diseases".)
MECHANISM OF ACTION
Natalizumab blocks leukocyte migration from the blood vessels to sites of inflammation by inhibiting the action of cell adhesion molecules . Cell adhesion molecules represent a heterogeneous group of transmembrane molecules expressed on numerous cell types, including endothelial cells and leukocytes. Cell adhesion molecules promote the transmigration of leukocytes across the endothelial cell. The particular molecule targeted by natalizumab is alpha-4 integrin, which is expressed on all circulating leukocytes except neutrophils.
INDICATIONS AND CONTRAINDICATIONS
Natalizumab is indicated for inducing and maintaining clinical response and remission in adult patients with Crohn disease. Patients being considered for natalizumab must have:
●Moderately to severely active Crohn disease
- Ghosh S, Goldin E, Gordon FH, et al. Natalizumab for active Crohn's disease. N Engl J Med 2003; 348:24.
- Sandborn WJ, Colombel JF, Enns R, et al. Natalizumab induction and maintenance therapy for Crohn's disease. N Engl J Med 2005; 353:1912.
- Sands BE. Leukocyte Anti-Trafficking Strategies: Current Status and Future Directions. Dig Dis 2017; 35:13.
- Kappos L, Bates D, Hartung HP, et al. Natalizumab treatment for multiple sclerosis: recommendations for patient selection and monitoring. Lancet Neurol 2007; 6:431.
- Ransohoff RM. Natalizumab for multiple sclerosis. N Engl J Med 2007; 356:2622.
- http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm398065.htm (Accessed on May 21, 2014).
- Ford AC, Sandborn WJ, Khan KJ, et al. Efficacy of biological therapies in inflammatory bowel disease: systematic review and meta-analysis. Am J Gastroenterol 2011; 106:644.
- Targan SR, Feagan BG, Fedorak RN, et al. Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial. Gastroenterology 2007; 132:1672.
- 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.
- Verbeeck J, Van Assche G, Ryding J, et al. JC viral loads in patients with Crohn's disease treated with immunosuppression: can we screen for elevated risk of progressive multifocal leukoencephalopathy? Gut 2008; 57:1393.
- Biogen Idec Medical Information Web Site. https://medinfo.biogenidec.com/medinfo/registration/reguser.do (Accessed on January 19, 2011).