GASTROENTEROLOGY 1995;108:345-349 Mesalamine in the Prevention of Endoscopic Recurrence After Intestinal Resection for Crohn's Disease CORRADO BRIGNOLA,* MARIO COTTONE,* ANGELO PERA, § SANDRO ARDIZZONE, JI MARIA LIA SCRIBANO, IT ROBERTO DE FRANCHIS, # AGESILAO D'ARIENZO,** GIUSEPPE D'ALBASIO,** DANIELE PENNESTRI, §§ and THE ITALIAN COOPERATIVE STUDY GROUP *lstituto di Clinica Medica e Gastroenterologia, Universit~ di Bologna, Bologna; *Divisione di Medicina, Ospedale "Cervello," Palermo; ~Divisione di Gastroenterologia, Ospedale "Le Molinette," Torino; JIServizio di Gastroenterologia, Ospedale "L, Sacco," Milano; ~Divisione di Gastroenterologia, Ospedale "Regina Margherita," Roma; #Clinica Medica III, Universit& di Milano, Milano; **Divisione di Gastroenterologia, It facolt~ di Medecina, Universit~ di Napoli, Napoli; **Divisione di Gastroenterologia, Ospedale "Careggi," Firenze; and §~Yamanouchi Pharma, Carugate-Milano, Italy Background~Aims: Recurrence of lesions of Crohn's disease of the ileum within i year after so-called cura- tive resection was well documented by endoscopy in 73%-93% of cases. This study investigated the effi- cacy of mesalamine in reduction of endoscopic recur- rence after surgery. Methods: In a double-blind, multicenter clinical trial, 87 patients were treated with 3 g/day mesalamine (Pentasa) or with placebo within 1 month after surgery. After 12 months of treatment, severity of endoscopic lesions was recorded with a five- point score; when it was not possible to reach the anastomosis by endoscopy, a barium enema was per- formed. Results: Seventeen clinical relapses (seven in the mesalamine group) were recorded. After 12 months, the endoscopic lesions were less frequent and less severe in the mesalamine group than were those in the placebo group (Z 2, 13.5; P < 0.008). The overall rate of severe recurrence (score of 3-4 on endoscopy or radiological documentation) was 24% in the mesala- mine group and 56% in the placebo group (Z 2, 8.57; P < 0.004; difference 32%; 95% confidence interval, 22-52). The odds ratio for active treatment was 4.1. Conclusions: This study shows that mesalamine is use- ful in decreasing the rate and severity of endoscopic recurrences after curative surgery for ileal Crohn's dis- ease. C rohn's disease (CD) frequently requires surgery for complications such as strictures, fistulas, and ab- scesses. The percentage of patients whose ileal region is involved having undergone surgery by 10 years after the first symptoms appear reaches 86%. 1 Unfortunately, resection does not offer cure; 73%-93% of cases show reappearance of lesions well documented by endoscopy within 1 year after surgery, and in 34%-86%, subse- quent clinical relapse is described to occur within 3 years. 2'5 Patients having had so-called curative resection repre- sent a good subset in whom preventive treatment may be tested. In fact, until now, no drug has been shown as being unequivocally effective in reducing relapse if used for CD in remission. In particular, trials of mesalamine as maintenance treatment in patients in remission have furnished contradictory results4-6; in patients treated im- mediately after surgery, four preliminary reports are available: two unsuccessful 7'8 and two with encouraging results. 9,1° We undertook a double-blind multicenter clinical trial with mesalamine to investigate the efficacy of this drug in reduction of endoscopic recurrence of the disease after curative resection of the ileal or ileocecal lesion. Materials and Methods This study was a double-blind, placebo-controlled, multicenter clinical trial. We included patients with so-called curative resection, such as those who have undergone removal of all macroscopic disease in the ileal or ileocecal region. Pa- tients with localization of CD in another region or having resection of >100 cm were excluded. After giving informed consent and within 1 month after surgery, patients were ran- domly assigned to receive 2 tablets 3 times a day for 12 months. The tablets were either Pentasa (Yamanouchi Pharma S.p.A., Carugate-Milano, Italy) (500-mg tablets), 3 g/day, or identical placebo tablets. Randomization was stratified by the number of previous intestinal resections (1 or more). Each center received material for at least 4 cases labeled with a patient code number according to a randomization made in balanced blocks. Between June 1990 and December 1991, 87 patients were recruited from 8 Italian centers (4 patients from each of 3 centers, 10 patients from 2, and at least 14 patients from the others). After 1 year of treatment, a colonoscopy Abbreviations used in this paper: CI, confidence interval; OR, odds ratio. © 1995 by the American Gastroenterological Association 0016-5085/95/$3.00