Natalizumab Reduces the Rate of Hospitalization in Moderate to Severe Crohnʼs Patients: Data from the ENACT and ENCORE Trials (2009)

Purpose: Hospitalization accounts for a large proportion of the cost of Crohn's disease (CD) management. This study evaluated the effect of natalizumab (NAT) on the rate of hospitalization during induction and maintenance treatment. Methods: NAT induction was studied using pooled data from the ENACT-1 and ENCORE trials of moderate to severe CD patients who were randomized to intravenous NAT 300mg or placebo (PBO) every 4 weeks for 3 doses. The maintenance analysis was conducted on NAT responders in ENACT-1 who were re-randomized and followed for an additional 48 weeks of therapy in ENACT-2. Data on patients losing response in ENACT-2 who rolled over to an open label study (ENABLE) supplemented the ENACT-2 data. Hospitalizations in each study were identified from adverse event reports. The rates of all-cause hospitalization (ACH) and CD-related hospitalizations (CDH) per 100 patients (/100P) over the 84-day induction period and the 336-day maintenance periods were evaluated. Further analyses were performed in an a priori defined subpopulation that had received prior anti-TNF alpha therapy and had evidence of active inflammation (C-reactive protein>2.87mg/L). Results: The table below provides the ACH and CDH rates for the NAT and PBO patients comprising the full samples and the prior anti-TNF samples in the induction and maintenance studies. Hospitalization rates were significantly lower in the patients treated with NAT. Evaluation of surgery rates was hampered by a low number of events. Among patients who had received prior anti-TNF therapy there was no difference in surgery rates between the treatment groups during induction (rate ratio 1.33, p=0.81), while during maintenance therapy Nat was associated with a trend toward a 55% reduction in surgeries (p=0.22). Conclusion: In the induction studies, NAT was associated with a 34% reduction in the rate of ACH and a 31% reduction in CDH compared to PBO. The risk of hospitalization was higher in patients receiving prior anti-TNF therapy and the benefit associated with NAT was even greater in this more difficult to treat patient population, with rate reductions of 56% and 55%, respectively. During the 336-day maintenance period, NAT was associated with a 44% reduction in the ACH rate and a 58% reduction in the CDH rate. Again, NAT was associated with greater reductions in hospitalizations in patients previously treated with anti-TNF therapy, with ACH rates reduced by 60% and CDH rates reduced by 75%. Disclosure: Dr Siegel reports serving as a consultant and an Advisory Committee/Board Member to Elan and Biogen Idec; Dr Sands reports serving as a consultant and an Advisory Committee/Board Member to Elan and Biogen Idec; Dr Feagan reports serving as a consultant and an Advisory Committee/Board Member to Elan and Biogen Idec; Dr Sandborn reports serving as a consultant and an Advisory Committee/Board Member to Elan and Biogen Idec; Dr Hass is an employee of Elan; Dr Niecko is an employee of Niecko Health Economics. These studies were sponsored by Elan Pharmaceuticals, Inc. and Biogen Idec, Inc.Table