Infliximab maintenance therapy for fistulizing Crohn's disease.
BACKGROUND
Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas.


METHODS
We performed a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn's disease and one or more draining abdominal or perianal fistulas of at least three months' duration. Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0, 2, and 6. A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then randomly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54. The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent randomization.


RESULTS
The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance (more than 40 weeks vs. 14 weeks, P<0.001). At week 54, 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas, as compared with 36 percent of patients in the infliximab maintenance group (P=0.009).


CONCLUSIONS
Patients with fistulizing Crohn's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks.
Gastrointestinal Unit, Massachusetts General Hospital, and Harvard Medical School, Boston 02114, USA.
Bruce E
BE
Sands
Frank H
FH
Anderson
Charles N
CN
Bernstein
William Y
WY
Chey
Brian G
BG
Feagan
Richard N
RN
Fedorak
Michael A
MA
Kamm
Joshua R
JR
Korzenik
Bret A
BA
Lashner
Jane E
JE
Onken
Daniel
D
Rachmilewitz
Paul
P
Rutgeerts
Gary
G
Wild
Douglas C
DC
Wolf
Paul A
PA
Marsters
Suzanne B
SB
Travers
Marion A
MA
Blank
Sander J
SJ
van Deventer
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy*; D017577:Cutaneous Fistula / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004361:Drug Tolerance; D005260:Female; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab; D007262:Infusions, Intravenous; D007412:Intestinal Fistula / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012003:Rectal Fistula / Q000188:drug therapy / Q000209:etiology; D012008:Recurrence; D012074:Remission Induction; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D005765:Gastrointestinal Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab