Amongst the available therapies for moderate to severe Crohn's disease (CD) patients who are refractory to conventional therapy, anti-TNF blockers are the most effective biological treatment option. However, many patients experience a primary or secondary non-response to anti-TNF therapy, creating the need for alternative biological drugs that target different mechanisms of action and inflammatory pathways. Natalizumab, the first non-anti-TNF biological drug to be approved for treatment of CD patients, is a recombinant humanized antibody that targets the α4-subunit of both α4β1 and α4β7 integrins, thus preventing activated leukocyte homing to the intestinal mucosa. Areas covered: This article summarizes the pathophysiological background and the efficacy and safety data of natalizumab, as well as the regulatory issues surrounding it. Expert opinion: Natalizumab represents an effective therapy for refractory CD patients. However, the rare but serious event of progressive multifocal leukoencephalopathy occurrence has compromised its widespread use. The subsequent advent of more specific anti-integrin drugs (i.e. vedolizumab) that carry a more favorable safety profile further reduces the clinical indications for natalizumab. The regulatory process for natalizumab distribution and monitoring in the US may provide a forum for discussion on how to optimally manage use of drugs that offer clinical benefits to patients, while minimizing associated risks.
Keywords: Crohn’s disease; Natalizumab; efficacy; progressive multifocal leukoencephalopathy; safety.