Prevalence of Antibodies Against JC Virus in Patients With Refractory Crohn's Disease and Effects of Natalizumab Therapy

Abstract

Background & aims: Natalizumab, a humanized antibody against the α4 integrin subunit, effectively induces and maintains remission in patients with Crohn's disease (CD) refractory to conventional treatments. Progressive multifocal leukoencephalopathy is a rare but fatal brain infection caused by John Cunningham (JC) virus and has been associated with natalizumab use. We assessed the prevalence of and risk factors for antibodies to JC virus in serum of patients with refractory CD who were candidates for, or already were receiving, natalizumab. We also assessed the effects of natalizumab treatment of these patients.

Methods: In a retrospective study, we analyzed clinical charts from 191 patients with CD (74 males; mean age, 38.7 y; mean duration of disease, 14.9 y) tested for serum JC virus antibody from December 2012 through May 2014 at 2 medical centers in the United States. We calculated JC virus antibody prevalence and compared the characteristics of patients who tested negative vs those who tested positive, to identify risk factors. We also assessed the rate of subsequent natalizumab use, surgery, and seroconversion during natalizumab therapy.

Results: A total of 129 of the patients (67.5%) tested positive for serum JC virus antibody. Multivariate analysis showed that past use of thiopurine was a risk factor for testing positive for JC virus antibody (odds ratio, 7.8; 95% confidence interval, 2.0-30.4; P = .003). Twenty-two of the patients who tested negative for JC virus antibody (35.5%) and 16 of the 129 patients who tested positive (12.4%) had been treated with natalizumab. Cox regression analysis determined that natalizumab use was the only factor associated with avoiding subsequent surgery (hazard ratio, 0.23; 95% confidence interval, 0.06-0.98). Seroconversion (from testing negative to positive for JC virus antibody) occurred in 1 of the 22 patients (4.5%) who initially tested negative during natalizumab therapy.

Conclusions: The prevalence of CD patients exposed to JC virus is comparable with that of the general population. In this retrospective study, prior thiopurine use was associated with an increased risk for testing positive for JC virus antibody. Natalizumab use reduced the risk of subsequent surgery.

Keywords: Biologic; IBD; Inflammatory Bowel Disease; PML; Thiopurine.