Infliximab for Ulcerative Colitis
Infliximab significantly reduced the rate of colectomy in patients who had severe or moderately severe ulcerative colitis that was refractory to conventional treatment, reported Gunnar Järnerot, M.D., of Örebro (Sweden) University Hospital, and associates.
In an interim analysis of a randomized, double-blind trial that was ended early because of slow enrollment and ethical issues, significantly fewer patients (7 of 24) who received an infusion of infliximab had a colectomy within 90 days than did patients who received placebo (14 of 21). Treatment with infliximab was associated with a significant, nearly fivefold higher likelihood of remaining free of colectomy than was placebo. Two additional patients in each group had a colectomy after 6 months of follow-up (Gastroenterology 2005;128:1805–11).
Maintenance treatment with repeated infliximab infusions will probably be needed for patients with ulcerative colitis, just as it has been for patients with Crohn's disease, especially “in patients who escape a colectomy to avoid further hospitalizations and risk of later surgery,” Geert D'Haens, M.D., of the Imelda GI Clinical Research Center, Bonheiden, Belgium, said in an editorial (Gastroenterology 2005;128:2161–4). Centocor, the maker of infliximab (Remicade), did not sponsor the trial.
Mycobacterial Cause of Crohn's?
Mycobacterium avium subspecies paratuberculosis is present in gut tissues from a significantly greater percentage of patients with Crohn's disease than from those with ulcerative colitis or diseases not specifically related to inflammatory bowel disease, according to a prospective study.
Nested polymerase chain reaction detected the DNA sequence IS900, which identifies Mycobacterium avium subspecies paratuberculosis (MAP), in 52 of 100 diseased biopsy samples from patients with Crohn's disease vs. 2 of 100 samples from patients with ulcerative colitis and 5 of 100 normal tissue biopsies from patients with diseases not specifically related to inflammatory bowel disease (Gut 2005;54:944–9).
Frank Autschbach, M.D., of the University of Heidelberg (Germany) and his colleagues reported that in patients with Crohn's disease, MAP was significantly more prevalent in diseased locations of the colon than the ileum, and in patients who had the disease for less than 15 years, compared with those who had it for 15 years or more. MAP did not occur more often with either stricturing or penetrating phenotypes of the disease. The investigators' findings are in direct contrast with reports on strong associations between polymorphisms of the NOD2 and CARD15 genes and patients with early-onset ileal Crohn's disease with a stricturing phenotype, said R. Balfour Sartor, M.D., of the University of North Carolina, Chapel Hill, in an editorial (Gut 2005;54:896–8).
Maintaining Remission in Crohn's
Withdrawal from azathioprine is not equivalent to continued therapy with the drug in Crohn's disease patients who have been in clinical remission for at least 3.5 years while on azathioprine, according to a randomized, double-blind trial.
Marc Lémann, M.D., of the Centre Hospitalier Universitaire Lariboisière-Saint-Louis, Paris, and his associates found that 3 (8%) of 40 patients who continued to receive azathioprine relapsed after 18 months vs. 9 (21%) of 43 patients on placebo. The trial was designed to determine whether withdrawal from azathioprine had an efficacy similar to continued treatment with azathioprine. The investigators determined that baseline levels of C-reactive protein of 20 mg/L or greater and hemoglobin less than 12 g/dL, as well as 50 or more months without steroids, were independent factors associated with a higher rate of relapse during the 18-month study (Gastroenterology 2005;128:1812–8).
Sleep Apnea: Risk for Liver Injury
Severe obstructive sleep apnea appears to be a risk factor for elevated liver enzymes and steatohepatitis, independent of body weight, reported Florence Tanné of Hôpital Saint-Antoine, Paris, and colleagues.
In a prospective study of 163 patients who were evaluated for clinical suspicion of obstructive sleep apnea (OSA), the researchers found that OSA was severe in 44 patients, moderate in 84, and absent in 35 patients. Body mass index and severe OSA were independently associated with elevated liver enzymes in a multivariate analysis. Of 32 patients with elevated liver enzymes, 18 underwent liver biopsy (Hepatology 2005;41:1290–6).
In 12 of 13 patients with a liver biopsy who had steatosis, evidence of steatohepatitis (lobular necrosis or hepatocyte ballooning) was seen. Patients with severe OSA had significantly higher levels of insulin, greater insulin resistance, and higher percentages of steatosis and scores of lobular necrosis and fibrosis than did those with either moderate OSA or no OSA.