Prophylaxis of postoperative relapse in Crohn's disease with mesalamine: European Cooperative Crohn's Disease Study VI.
OBJECTIVE
This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection.


METHODS
In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model.


RESULTS
Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003).


CONCLUSIONS
Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease.
Lochs
H
H
IV Medizinische Klinik, Universitätsklinikum Charité, Humboldt Universität, Berlin, Germany. herbet.lochs@charite.de
Mayer
M
M
Fleig
W E
WE
Mortensen
P B
PB
Bauer
P
P
Genser
D
D
Petritsch
W
W
Raithel
M
M
Hoffmann
R
R
Gross
V
V
Plauth
M
M
Staun
M
M
Nesje
L B
LB
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D003424:Crohn Disease / Q000517:prevention & control* / Q000601:surgery*; D004311:Double-Blind Method; D005060:Europe; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012008:Recurrence; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010919:Placebos; D019804:Mesalamine