Efficacy and safety of natalizumab for anti-TNF refractory Crohn's disease

BACKGROUND: Anti-tumor necrosis factor (TNF) agents have changed the paradigm of Crohn's disease (CD) management; however, a substantial number of patients are either primary or secondary non-responders. Natalizumab is an anti-integrin inhibitor that has shown effectiveness for the treatment of CD, though its use is limited due to the risk of progressive multifocal leukoencephalopathy (PML). We aimed to assess the efficacy and safety of natalizumab in CD and further evaluated the utility of endoscopic assessment during treatment.
METHODS: Retrospective case review of 49 CD patients receiving natalizumab.
RESULTS: Forty-seven of 49 patients were anti-TNF failures. Median duration of natalizumab treatment was 7 months; twenty-four patients (49%) were continuing therapy, and twenty-five discontinued due to lack of response, side effects, or positive JCV antibody, but no case of PML occurred. Seventeen patients (35%) continued treatment for longer than 12 months, and non-penetrating disease phenotype was a predictor of response. Thirty-two patients underwent at least one ileocolonoscopy before or during treatment. Those with a greater baseline Simple Endoscopic Score for Crohn's Disease (SESCD) were less likely to respond to treatment. Mucosal healing (decrease of SESCD of >70%) was achieved in 11 of 26 patients (42.3%), and correlated with an improved long-term outcome.
Conclusion: Natalizumab is an efficacious and safe treatment for anti-TNF refractory CD. The degree of endoscopic inflammation correlates to response to natalizumab and maintenance of remission.