Ustekinumab induction and maintenance therapy in refractory Crohn's disease.
BACKGROUND
In patients with Crohn's disease, the efficacy of ustekinumab, a human monoclonal antibody against interleukin-12 and interleukin-23, is unknown.


METHODS
We evaluated ustekinumab in adults with moderate-to-severe Crohn's disease that was resistant to anti-tumor necrosis factor (TNF) treatment. During induction, 526 patients were randomly assigned to receive intravenous ustekinumab (at a dose of 1, 3, or 6 mg per kilogram of body weight) or placebo at week 0. During the maintenance phase, 145 patients who had a response to ustekinumab at 6 weeks underwent a second randomization to receive subcutaneous injections of ustekinumab (90 mg) or placebo at weeks 8 and 16. The primary end point was a clinical response at 6 weeks.


RESULTS
The proportions of patients who reached the primary end point were 36.6%, 34.1%, and 39.7% for 1, 3, and 6 mg of ustekinumab per kilogram, respectively, as compared with 23.5% for placebo (P=0.005 for the comparison with the 6-mg group). The rate of clinical remission with the 6-mg dose did not differ significantly from the rate with placebo at 6 weeks. Maintenance therapy with ustekinumab, as compared with placebo, resulted in significantly increased rates of clinical remission (41.7% vs. 27.4%, P=0.03) and response (69.4% vs. 42.5%, P<0.001) at 22 weeks. Serious infections occurred in 7 patients (6 receiving ustekinumab) during induction and 11 patients (4 receiving ustekinumab) during maintenance. Basal-cell carcinoma developed in 1 patient receiving ustekinumab.


CONCLUSIONS
Patients with moderate-to-severe Crohn's disease that was resistant to TNF antagonists had an increased rate of response to induction with ustekinumab, as compared with placebo. Patients with an initial response to ustekinumab had significantly increased rates of response and remission with ustekinumab as maintenance therapy. (Funded by Janssen Research and Development; CERTIFI ClinicalTrials.gov number, NCT00771667.).
Division of Gastroenterology, University of California San Diego, La Jolla, California 92093-0956, USA. wsandborn@ucsd.edu
William J
WJ
Sandborn
Christopher
C
Gasink
Long-Long
LL
Gao
Marion A
MA
Blank
Jewel
J
Johanns
Cynthia
C
Guzzo
Bruce E
BE
Sands
Stephen B
SB
Hanauer
Stephan
S
Targan
Paul
P
Rutgeerts
Subrata
S
Ghosh
Willem J S
WJ
de Villiers
Remo
R
Panaccione
Gordon
G
Greenberg
Stefan
S
Schreiber
Simon
S
Lichtiger
Brian G
BG
Feagan
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003424:Crohn Disease / Q000145:classification / Q000188:drug therapy*; D004311:Double-Blind Method; D004351:Drug Resistance; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D012720:Severity of Illness Index; D000079424:Tumor Necrosis Factor Inhibitors; D000069549:Ustekinumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000079424:Tumor Necrosis Factor Inhibitors; D000069549:Ustekinumab