Natalizumab in the treatment of Crohn’s disease patients

ABSTRACT

Introduction: 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:

• Natalizumab
• Crohn’s disease
• efficacy
• safety
• progressive multifocal leukoencephalopathy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

The authors are supported by the National Institutes of Health via the National Institute of Diabetes and Digestive and Kidney Diseases with grants DK042191, DK055812, DK091222 and DK097948.