Two mesalazine regimens in the prevention of the post-operative recurrence of Crohn's disease: a pragmatic, double-blind, randomized controlled trial.
BACKGROUND
The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response.


OBJECTIVE
To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease.


METHODS
The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi-square, Wilcoxon and Cox regression model tests were used, when appropriate.


RESULTS
Eighty-four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence.


CONCLUSIONS
A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post-operative endoscopic and clinical recurrence of Crohn's disease at 1 year of follow-up.
Caprilli
R
R
GI Unit, Department of Clinical Sciences, University of Rome La Sapienza, Rome, Italy. renzo.caprilli@uniroma1.it
Cottone
M
M
Tonelli
F
F
Sturniolo
G
G
Castiglione
F
F
Annese
V
V
Papi
C
C
Viscido
A
A
Cammà
C
C
Corrao
G
G
Latella
G
G
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D003424:Crohn Disease / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000009:adverse effects; D010349:Patient Compliance; D011183:Postoperative Complications / Q000517:prevention & control*; D012008:Recurrence; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine