Adalimumab induction therapy for Crohn disease previously treated with infliximab: a randomized trial.
BACKGROUND
Adalimumab, a fully human tumor necrosis factor (TNF) antagonist, is an effective treatment for patients with Crohn disease who are naive to the chimeric TNF antagonist, infliximab. No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent.


OBJECTIVE
To determine whether adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who have symptoms despite infliximab therapy or who cannot take infliximab because of adverse events.


METHODS
4-week, randomized, double-blind, placebo-controlled trial (November 2004 to December 2005).


METHODS
52 sites in the United States, Canada, and Europe.


METHODS
325 adults 18 to 75 years of age who had a history of Crohn disease for 4 months or more that was moderate to severe at baseline (Crohn's Disease Activity Index [CDAI] score, 220 to 450 points).


METHODS
Patients were randomly assigned to receive induction doses of adalimumab, 160 mg and 80 mg, at weeks 0 and 2, respectively, or placebo at the same time points.


METHODS
The primary end point was induction of remission at week 4. Decreases in CDAI score by 70 or more and 100 or more points (secondary end points) were also measured.


RESULTS
A total of 301 patients completed the trial. Twenty-one percent (34 of 159) of patients in the adalimumab group versus 7% (12 of 166) of those in the placebo group achieved remission at week 4 (P < 0.001). The absolute difference in clinical remission rates was 14.2 percentage points (95% CI, 6.7 to 21.6 percentage points). A 70-point response occurred at week 4 in 52% (82 of 159) of patients in the adalimumab group versus 34% (56 of 166) of patients in the placebo group (P = 0.001). The absolute difference in 70-point response rates was 17.8 percentage points (CI, 7.3 to 28.4 percentage points). Two of 159 patients in the adalimumab group and 4 of 166 patients in the placebo group discontinued treatment because of adverse events. No patients in the adalimumab group and 4 of 166 patients in the placebo group had a serious infection.


CONCLUSIONS
The trial did not directly compare alternative active treatments and did not evaluate maintenance of response or long-term immunogenicity of adalimumab.


CONCLUSIONS
Adalimumab induces remissions more frequently than placebo in adult patients with Crohn disease who cannot tolerate infliximab or have symptoms despite receiving infliximab therapy. For more information on adalimumab in Crohn disease, click here. ClinicalTrials.gov registration number: NCT00105300.
Sandborn
William J
WJ
Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. sandborn.william@mayo.edu
Rutgeerts
Paul
P
Enns
Robert
R
Hanauer
Stephen B
SB
Colombel
Jean-Frédéric
JF
Panaccione
Remo
R
D'Haens
Geert
G
Li
Ju
J
Rosenfeld
Marie R
MR
Kent
Jeffrey D
JD
Pollack
Paul F
PF
D000068879:Adalimumab; D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab