Adalimumab induces and maintains mucosal healing in patients with Crohn's disease: data from the EXTEND trial.
OBJECTIVE
We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD).


METHODS
A randomized, double-blind, placebo-controlled trial (extend the safety and efficacy of adalimumab through endoscopic healing [EXTEND]) evaluated adalimumab for induction and maintenance of mucosal healing in 135 adults with moderate to severe ileocolonic CD. The baseline degree of mucosal ulceration was documented by ileocolonoscopy. All patients received induction therapy (subcutaneous adalimumab 160/80 mg at weeks 0/2). At week 4, patients were randomly assigned to groups given 40 mg adalimumab or placebo every other week through week 52. Open-label adalimumab was given to patients with flares or no response, starting at week 8. Mucosal healing was reassessed by ileocolonoscopy at weeks 12 and 52.


RESULTS
Twenty-seven percent of patients receiving adalimumab had mucosal healing at week 12 (the primary end point) versus 13% given placebo (P = .056). At week 52, rates of mucosal healing were 24% and 0, respectively (P < .001). Remission rates, based on the Crohn's Disease Endoscopic Index of Severity, were 52% for adalimumab and 28% for placebo at week 12 (P = .006) and 28% and 3%, respectively, at week 52 (P < .001). Rates of clinical remission based on the Crohn's Disease Activity Index were greater among patients given continuous adalimumab therapy versus placebo at weeks 12 (47% vs 28%; P = .021) and 52 (33% vs 9%; P = .001). Five serious (1 during induction and 4 during open-label therapy) and 3 opportunistic infections (1 in each group during double-blind therapy and 1 during open-label therapy) were reported (n = 135).


CONCLUSIONS
Following induction therapy with adalimumab, patients with moderately to severely active CD who continue to receive adalimumab are more likely to achieve mucosal healing than those given placebo.
Department of Gastro-Enterologie, University Hospital of Gasthuisberg, Leuven, Belgium. paul.rutgeerts@uzleuven.be
Paul
P
Rutgeerts
Gert
G
Van Assche
William J
WJ
Sandborn
Douglas C
DC
Wolf
Karel
K
Geboes
Jean-Frédéric
JF
Colombel
Walter
W
Reinisch
Ashish
A
Kumar
Andreas
A
Lazar
Anne
A
Camez
Kathleen G
KG
Lomax
Paul F
PF
Pollack
Geert
G
D'Haens
D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014945:Wound Healing
D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000068879:Adalimumab