IBD Watch^®

^{Timely Information for Practicing Physicians}

 OCTOBER 2004

CROHN'S DISEASE (CD)

Postoperative therapy.  The results of 2 randomized trials investigating postoperative maintenance therapy in patients with CD have recently been reported.  In the first study, Hanauer et al randomized 131 CD patients who had undergone resection and ileocolonic anastomosis to receive 6 mercaptopurine (MP) (50 mg/day), mesalamine (3 g/day), or placebo.  Due to patient withdrawals, only 69% of patients were evaluable for clinical recurrence.  The clinical recurrence rates at 2 years were 77%, 58%, and 50% for evaluable patients treated with placebo, mesalamine, and 6-MP, respectively.  The endoscopic recurrence rates at 2 years were 64%, 63%, and 43% for patients treated with placebo, mesalamine, and 6-MP, respectively.  The authors concluded that 6-MP 50 mg daily was more effective than placebo at preventing postoperative recurrence of CD.  In an open-label study, Ardizzone and colleagues randomized 142 patients who had undergone conservative surgery for CD to receive azathioprine (2 mg/kg/day) or mesalamine (3 g/day).  The observed rates of clinical recurrence at 2 years for azathioprine- and mesalamine-treated patients were similar (17% vs. 28%).  In the editorial, Sandborn and Feagan argue that the conclusion by Hanauer et al that 6-MP is effective postoperative therapy is not supported by robust data.  They point out that the 95% confidence intervals overlap for all 3 treatment groups in every analysis and that the p-value for clinical recurrence rates was not adjusted for multiple comparisons.  Other concerns about the conduct of the study included the use of unvalidated clinical assessments, the failure to specify a specific primary endpoint, and the amount of missing data resulting from the high patient withdrawal rate.  Sandborn and Feagan conclude that the study conducted by Ardizzone et al was a well-designed trial that failed to show superiority of azathioprine over mesalamine.  In their opinion the efficacy of mesalamine is insufficient to warrant its routine use and they strongly urge that an adequately powered study to show statistical significance for azathioprine and/or 6-MP vs. placebo be performed to clarify the proper treatment of CD patients postsurgically.  (Hanauer SB, et al. Gastroenterology 2004;127:723-729; Ardizzone S, et al. Gastroenterology 2004;127:730-740; Sandborn WJ and Feagan BG. Gastroenterology 2004;127:990-993)

Immunosuppressive drugs decrease recurrence rate after second resection.  Alves et al conducted a small trial (n = 24) in which patients who had undergone a second resection for ileocolonic anastomotic recurrence of CD were treated with immunosuppressive agents (azathioprine, 6-MP, or methotrexate) (n = 12) or salicylates/no treatment (n = 12).  They observed a lower recurrence rate at 3 years for the patients who received immunosuppressive agents compared to those patients in the control group (p < 0.05).  The authors suggest that these results warrant further prospective study of immunosuppressive therapy for the prevention of second postoperative CD recurrence.  (Alves A, et al. Inflammatory Bowel Diseases 2004;10:491-495)

ULCERATIVE COLITIS (UC)

Treatment of cuffitis following restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA).  An IPAA normally leaves a 1-2 cm rectal cuff and recurrence of UC (cuffitis) in this transitional zone may mimic pouchitis.  Shen and coworkers at the Cleveland Clinic treated 14 consecutive patients who had developed cuffitis with mesalamine suppositories 500 mg bid for a mean of 3.2 months (range, 1-9 months).  No systemic or topical adverse events were reported.  Mesalamine therapy resulted in reductions of the total Cuffitis Activity Index score (adapted from the Pouchitis Disease Activity Index) and the scores of each of its components (symptoms, endoscopy, histology).  In addition, 92% of patients with bloody bowel movements and 70% of patients with arthralgias improved after therapy.  The findings of this small clinical experience indicate that mesalamine suppositories are well tolerated and are effective in the treatment of UC patients with cuffitis.  (Shen B, et al. Am J Gastroenterol 2004;99:1527-1531)

INFLAMMATORY BOWEL DISEASE (IBD)

HLA disparity and disease activity.  Kane and others studied the relationship between maternal-fetal HLA disparity and the course of IBD.  Among 50 pregnancies in 38 women, the following disparities were observed: (1) 42 pregnancies (84%) were disparate at the DRB1 locus; (2) 34 pregnancies (68%) were disparate at the DQ locus; and (3) 31 pregnancies (62%) were disparate at both the DRB1 and DQ loci.  While no differences in average disease score or overall activity were noted in pregnancies disparate at only the DRB1 or the DQ locus, differences were found in pregnancies disparate at both loci.  Logistic regression identified prepartum disease activity and disparity at both DRB1 and DQ loci as independent predictors of IBD activity during pregnancy.  These data indicate that the course of IBD is variable during pregnancy and maternal immune response to paternal HLA antigens plays a role in pregnancy-induced remission.  (Kane S, et al. Am J Gastroenterol 2004;99:1523-1525)

Total and cancer mortality in UC vs. CD patients.  Masala et al report long-term follow-up (median 15 years) of patients with UC (n = 689) or CD (n = 231) in a population-based study in Florence, Italy.  Using age, sex, and calendar-specific national and local mortality rates, CD patients had 50% increased mortality due to gastrointestinal diseases, all cancers, and lung cancers.  UC patients had a significantly reduced total mortality due to lower cardiovascular mortality and lung cancer mortality.  These divergent patterns of mortality correlated with differences in smoking habits between CD and UC patients.  No evidence of increased mortality for colon cancer was observed in this series.  The authors concluded that physicians should consider the cessation of cigarette smoking to be a priority for CD patients.  (Masala G, et al. Gut 2004;53:1309-1313)

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