Natalizumab for the treatment of active Crohn's disease: results of the ENCORE Trial.
OBJECTIVE
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 (> or =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 < or = .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.
Targan
Stephan R
SR
Inflammatory Bowel Disease Center and Division of Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California 90048, USA. targans@cshs.org
Feagan
Brian G
BG
Fedorak
Richard N
RN
Lashner
Bret A
BA
Panaccione
Remo
R
Present
Daniel H
DH
Spehlmann
Martina E
ME
Rutgeerts
Paul J
PJ
Tulassay
Zsolt
Z
Volfova
Miroslava
M
Wolf
Douglas C
DC
Hernandez
Chito
C
Bornstein
Jeffrey
J
Sandborn
William J
WJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002097:C-Reactive Protein / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007125:Immunogenetics; D007249:Inflammation / Q000503:physiopathology; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab; D011788:Quality of Life; D012074:Remission Induction / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000069442:Natalizumab; D002097:C-Reactive Protein