Gastroenterology

Gastroenterology

Volume 132, Issue 5, May 2007, Pages 1672-1683
Gastroenterology

Clinical–alimentary tract
Natalizumab for the Treatment of Active Crohn’s Disease: Results of the ENCORE Trial

https://doi.org/10.1053/j.gastro.2007.03.024Get rights and content

Background & Aims: A randomized placebo-controlled trial evaluated the efficacy of natalizumab induction therapy in patients with Crohn’s disease. Methods: Patients (N = 509) with moderately to severely active Crohn’s disease and active inflammation characterized by elevated C-reactive protein concentrations were randomized (1:1) to receive natalizumab 300 mg or placebo intravenously at Weeks 0, 4, and 8. The primary end point was induction of response (≥70-point decrease from baseline in the Crohn’s Disease Activity Index score at Week 8 sustained through Week 12). Additional efficacy end points included the proportion of patients with sustained remission (Crohn’s Disease Activity Index score <150 points) and response or remission over time. Results: Response at Week 8 sustained through Week 12 occurred in 48% of natalizumab-treated patients and 32% of patients receiving placebo (P < .001). Sustained remission occurred in 26% of natalizumab-treated patients and 16% of patients receiving placebo (P = .002). Week 4 response rates were 51% for natalizumab and 37% for placebo (P = .001). Responses remained significantly higher at subsequent assessments (P < .001) in natalizumab-treated patients. Natalizumab-treated patients also had significantly higher remission rates at Weeks 4, 8, and 12 (P ≤ .009). The frequency and types of adverse events were similar between treatment groups. Conclusions: Natalizumab induced response and remission at Week 8 that was sustained through Week 12. Response and remission rates for natalizumab were superior to those for placebo at Weeks 4, 8, and 12, demonstrating the early and sustained efficacy of natalizumab as induction therapy in patients with elevated C-reactive protein and active Crohn’s disease. Natalizumab was well tolerated in this study.

Section snippets

Patients and Methods

Selected investigators and employees of Elan Pharmaceuticals, Inc (San Diego, CA), and Biogen Idec (Cambridge, MA) designed the ENCORE study. The investigator authors had access to all data, participated in the analysis and interpretation of these data, and were members of the publication committee. The manuscript was written by a publication committee (with the assistance of a medical writer), which included authors from the group of investigators. The authors verified the completeness and

Patient Characteristics

A total of 832 patients were screened; of these, 509 were eligible for randomization at Week 0 (Figure 2). The most common reason for a patient to fail screening was a CRP concentration below the ULN, which occurred in 171 patients (21% of the entire population screened for the trial). Patients were randomly assigned to receive placebo (250 patients) or natalizumab (259 patients). Data for all patients receiving study drug were included in the safety analysis (N = 510). One patient received a

Discussion

The ENCORE trial met all prespecified primary, secondary, and tertiary end points. Results of the trial demonstrated that treatment with 3 infusions of natalizumab (300 mg) over 8 Weeks was effective for inducing response and remission in patients with moderately to severely active Crohn’s disease and objective evidence of inflammation. The ENCORE trial required patients to be in response at 2 consecutive monthly assessments to meet the primary end point criteria. Response was achieved by Week

References (22)

  • W.J. Sandborn et al.

    Natalizumab induction and maintenance therapy for Crohn’s disease

    N Engl J Med

    (2005)
  • Cited by (0)

    Supported by a research grant from Elan Pharmaceuticals, Inc (San Diego, CA), and Biogen Idec (Cambridge, MA).

    1

    P.R., B.F., S.T., R.P., D.P., and W.S. have served as consultants for Elan Pharmaceuticals.

    2

    P.R., S.T., B.L., R.P., and W.S. have participated in continuing medical education events supported by unrestricted educational grants from Elan Pharmaceuticals, Inc, and Biogen Idec.

    3

    C.H. and J.B. are employees of Elan Pharmaceuticals, Inc, and report owning stock options.

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