IBD Watch®
Timely Information for Practicing Physicians
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SEPTEMBER 2005 ULCERATIVE COLITIS (UC) Low-dose oral microemulsion cyclosporin. De Saussure et al used low-dose oral microemulsion cyclosporin to treat 16 patients with severe steroid-refractory UC. Dosages were adapted according to a standard protocol that targeted a blood cyclosporin concentration of 100-200 ng/mL. Patients without a clinical response on day 8 of therapy were scheduled for colectomy. Clinical responses were achieved in 14 (88%) patients. The mean clinical activity index score decreased from 11.8 at baseline to 4.1 on day 8. Mean C-reactive protein levels were also reduced from 50.3 mg/L at baseline to 9.7 mg/L at the end of treatment. One patient developed an acute elevation of transaminases that resulted in the discontinuation of further ciclosporin therapy. Otherwise, the low-dose oral microemulsion of cyclosporin was well tolerated. These findings indicate that oral microemulsion cyclosporin treatment of patients with severe, steroid-refractory UC may achieve similar efficacy to that attained with high-dose intravenous cyclosporin. Controlled trials are needed. (De Saussure P, et al. Aliment Pharm Ther 2005;22:203-208) Studies of RDP58. Travis and others report the results of 2 multicenter, randomized, double-blind trials of RDP58, a novel oral decapeptide that inhibits the production of proinflammatory cytokines by disrupting MAPK signaling, in patients with mild to moderately active UC. In the first study, 34 patients were randomized (1:2) to receive RDP58 100 mg or placebo. In the second study, 93 patients were randomized to receive RDP58 200 mg, RDP58 300 mg, or placebo. RDP58 at a dose of 100 mg was not observed to be effective. However, treatment successes were realized with the higher doses of RDP58 (200 and 300 mg) that were associated with significant improvements in histological scores compared to placebo (p = 0.002). The development of adverse events was similar between the RDP58 arms and the placebo arm. These studies indicate that higher doses of RDP58 are potentially effective therapy for mild to moderate UC. (Travis S, et al. Inflamm Bowel Dis 2005;11:713-719) CROHN'S DISEASE (CD) Budesonide for maintenance remission therapy. Sandborn et al analyzed the pooled data from 4 identically designed double-blind trials in which 380 patients with CD in remission (CDAI ≤ 150) were randomized to receive 6 mg of oral budesonide daily, 3 mg of oral budesonide daily, or placebo daily for 12 months. The median time to relapse (increase in CDAI of 60 points to > 150) for the budesonide 6 mg, budesonide 3 mg, and placebo groups were 268, 170, and 154 days, respectively (p = 0.0072). The reporting of adverse events was similar between the treatment groups. These results show that budesonide 6 mg daily maintenance therapy prolongs the median time to relapse in CD patients in remission. (Sandborn W, et al. Am J Gastroenterol 2005;100:1780-1787) Capsule endoscopy vs. enteroclysis. Riccardo Marmo and associates report the results of a study in which 31 patients with proven CD underwent enteroclysis followed by wireless capsule endoscopy (WCE). The radiologist who performed the small bowel enema was blinded to the results of the diagnostic endoscopy and the gastroenterologist who interpreted the WCE video was blinded to the results of the enteroclysis. Abnormal findings were revealed in 8 (25.8%) patients by enteroclysis compared to 22 (71%) patients by WCE (p < 0.001). Among 16 patients with known terminal ileum disease, WCE and enteroclysis identified ileal involvement in 89% and 37% of patients, respectively (P < 0.001). In addition, proximal small bowel lesions were detected more frequently by WCE than enteroclysis (p < 0.001). These findings indicate that WCE is superior to enteroclysis for detecting the extent of small bowel CD. (Marmo R, et al. Clin Gastroenterol Hepatol 2005; epub) Natalizumab and progressive multifocal leukoencephalopathy (PML). Natalizumab, a humanized monoclonal antibody directed against α4 integrins, is being studied in clinical trials of CD and multiple sclerosis patients. Among 3000 patients who have participated in clinical trials, 3 patients have been reported to have developed PML, a deadly opportunistic infection of the central nervous system caused by reactivation of latent JC polyomavirus infection. These 3 cases are described in detail and are discussed by Berger and Koralnik in an accompanying article. Retrospective analysis of serum samples obtained from a CD patient over 4 years showed JC virus became detectable after 3 injections of natalizumab and then increased 10 fold after 2 more injections. By binding to the surface of lymphocytes, natalizumab may prevent the normal trafficking of lymphocytes and thus have led to the reactivation of JC virus (inflammatory infiltrates were absent from brain lesions). The authors recommend an analysis of JC viral load in patients treated with natalizumab to determine the predictive value of plasma levels of JC virus for the development of PML. The occurrence of PML in these patients was unexpected and these cases highlight the potential risks associated with immunomodulatory therapy that inhibits lymphocyte trafficking. (Berger JR and Koralnik IJ. N Engl J Med 2005;353:414-416) INFLAMMATORY BOWEL DISEASE (IBD) Azathioprine and 6-mercaptopurine (6-MP) and risk of lymphoma. Kandiel et al analyzed pooled data from 6 studies designed to evaluate cancer as an outcome of the treatment of IBD patients with azathioprine or 6-MP. Their evaluation suggests that IBD patients treated with azathioprine or 6-MP have a 4-fold increased risk of developing lymphoma. The increased risk of lymphoma may be due to exposure to azathioprine or 6-MP and/or the underlying disease. (Kandiel A, et al. Gut 2005;54:1121-1125) |
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