IBD Watch^®

^{Timely Information for Practicing Physicians}

  JULY 2005

CROHN'S DISEASE (CD)

Trial of sargramostim.  Preliminary data show that sargramostim, granulocyte-macrophage colony-stimulating factor (GM-CSF), stimulates cells in the intestinal immune system and may improve mucosal barrier function in the GI tract. These findings led Korzenik and colleagues to conduct a study in which 124 patients with moderate to severe active CD (CD Activity Index [CDAI] score of 220–475 points) were randomized in a 2:1 ratio to receive sargramostim 6 mg/kg or placebo subcutaneously for 56 days.  No significant difference in achieving a decrease from baseline of ≥70 points in CDAI score on day 57 (the primary endpoint) was observed between the sargramostim and placebo treatment groups (54% vs 44%; P=0.28). However, a greater percentage of patients in the sargramostim treatment group than in the placebo treatment group reached secondary endpoints of a decrease from baseline of ≥100 points (clinical response: 48% vs 26%; P=0.01) and ≥150 points (clinical remission: 40% vs 19%; P=0.01) in CDAI score on day 57. These clinical responses and remissions to sargramostim were rapid and sustained and were associated with significant improvements in disease-specific quality-of-life measurements. Additionally, improvements were seen in mucosal healing of sargramostim-treated patients. Mild to moderate injection-site reactions and bone pain were commonly associated with sargramostim therapy and led to the withdrawal of 4 of 81 patients from the study.  While the results of this study were negative for the primary endpoint, the positive findings for the secondary endpoints suggest that sargramostim treatment decreases disease severity in patients with moderate to severe active CD.  (Korzenik JR, et al. N Engl J Med. 2005;352:2193–2201)

Azathioprine maintenance.  Data from a previous open-label study suggested that CD patients in remission who have been treated with azathioprine for >3.5 years have a low risk of relapse when azathioprine is discontinued. Lemann and coworkers performed a study in which 83 CD patients in remission on azathioprine for ≥42 months were randomized to continue azathioprine therapy or to receive placebo for 18 months. Within 18 months of study treatment, 3 patients in the azathioprine maintenance group and 9 patients in the placebo group had relapsed. Kaplan-Meier estimates for relapse were 8% ± 4% and 21% ± 6% for the azathioprine and placebo groups, respectively. Thus, the hypothesis that placebo was inferior to azathioprine was not rejected (P=0.195). Multivariate analysis identified C-reactive protein level >20 mg/L at baseline, blood hemoglobin level <12 g/dL at base-line, and time without steroids of <50 months to be predictive factors for relapse. The authors concluded that azathioprine therapy should be continued beyond 3.5 years in responding CD patients.  (Lemann M, et al. Gastroenterology. 2005;128:1812–1818)

ULCERATIVE COLITIS (UC)

Infliximab rescue therapy.  Jarnerot and others randomized 45 patients with moderately severe to severe UC not responding to conventional treatment to receive infliximab 4 to 5 mg/kg or placebo. The treatments were given either on day 4 after the initiation of corticosteroid treatment, if the index criteria for fulminant UC had been fulfilled on day 3, or on days 6 to 8, if the index criteria for a severe or moderately severe acute attack of UC had been met on days 5 to 7. Colectomy within 3 months of randomization was required by 7 infliximab patients and 14 placebo patients; no deaths or serious side effects were reported. This study indicates that infliximab may be an effective and safe rescue therapy for patients with UC not responding to conventional treatment. Optimal dosing and need for maintenance therapy have yet to be elucidated.  (Jarnerot G, et al. Gastroenterology. 2005;128:1805–1811)

Combined oral and enema treatment with mesalamine.  In patients with mild to moderate extensive UC treated with standard oral aminosalicylates, the majority of clinical symptoms relate to disease activity in the distal colon. Therefore, Marteau and coworkers conducted a randomized, double-blind study of 127 patients with extensive mild to moderate UC to investigate whether the addition of mesalazine enema treatments to oral therapy had additional benefit.  All patients received oral mesalamine 4 g daily for 8 weeks. Patients were randomized to receive an enema at bedtime containing 1 g of mesalamine or placebo during the first 4 weeks of therapy. Improvement was observed in a greater proportion of patients in the mesalamine enema group than in the placebo enema group at both 4 weeks (89% vs 62%; P=0.0008) and 8 weeks (86% vs 68%; P=0.026). Remission at 8 weeks was achieved in 64% of patients in the mesalamine enema group and in 43% of patients in the placebo enema group (P=0.03). These results show that combination therapy with oral and enema mesalamine is superior to oral mesalamine treatment alone in UC patients with mild to moderate extensive disease.  (Marteau P, et al. Gut. 2005;54:960–965)

INFLAMMATORY BOWEL DISEASE (IBD)

Do patients receive optimal care?  Reddy and colleagues analyzed the medical records of IBD patients under the care of a gastroenterologist who sought a second opinion between January 2001 and April 2003 to determine whether these patients were receiving therapy in accordance with practice guidelines. The study population consisted of 67 consecutive patients (44 with CD, 21 with UC, and 2 in whom the diagnosis of IBD could not be confirmed). The authors found that many patients did not receive optimal medical therapy. Common inadequacies identified were suboptimal dosing of 5-ASA and immunomodulatory medications, prolonged use of corticosteroids, failure to use steroid-sparing agents, inadequate treatment to prevent metabolic bone disease, and inadequate screening for colorectal cancer.  (Reddy SI, et al. Am J Gastroenterol. 2005;100:1357–1361)

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