IBD Watch^®

^{Timely Information for Practicing Physicians}

 SEPTEMBER 2006

Neoplasms after 6-mercaptopurine (6-MP).  Disanti and others retrospectively reviewed the records of 600 IBD patients treated with 6-MP at one medical center between 1965 and 2002.  They identified 18 patients (the study group) with sustained leucopenia following 6-MP therapy.  The control group consisted of 54 IBD patients matched for age and sex.  Neoplasms developed in 4 (22%) patients in the study group (2 leukemias, 1 non-Hodgkin’s lymphoma, 1 breast cancer) and 4 (7%) patients in the control group (p = 0.10).  Further analysis revealed a statistically significant difference in the occurrence of hematologic malignancies between the study and control groups (p = 0.014).  These data from this small single-center study suggest that IBD patients with 6-MP-induced sustained leucopenia may be at risk for hematologic malignancies.  Further studies are needed to confirm these results.  (Disanti W, et al. Clin Gastroenterol Hepatol 2006 4:1025-1029)

Risk-benefit analysis of infliximab therapy.  Siegel et al constructed a decision analytic model to determine the risks and benefits of infliximab.  The analysis simulated 2 cohorts of 100,000 patients each in which one cohort received infliximab and the other cohort was given standard therapy.  The model predicted that at one year infliximab will lead to 12,216 more patients in remission, 4,255 fewer surgeries, and 33 fewer deaths from disease flares compared to the standard therapy cohort.  These benefits would occur at a cost of 201 more lymphomas and 249 more deaths related to complications associated with infliximab.  In addition, infliximab would result in more quality-adjusted life years (QALYs) than standard therapy.  This model shows that despite infliximab-related complications, the clinical improvement and fewer surgeries associated with infliximab therapy could result in an increase in QALYs.  In a properly selected CD population, the benefits of infliximab could outweigh its risks.  An editorial by Inadomi and Terdiman reviews the methodology of this analytic model.  They comment that the analysis suffers from a lack of long-term data beyond one year and the lack of an economic evaluation.  They also discuss the finding that infliximab provides greater QALYs despite an increase in mortality.  These authors conclude that this study provides an important and practical framework for CD patients and their physicians to make informed decisions concerning infliximab therapy.  (Siegel CA, et al. Clin Gastroenterol Hepatol 2006; 4: 1017-1024 and Inadomi JM and Terdiman J. Clin Gastroenterol Hepatol 2006;4:976-978)

Phenotype predicts recurrence rates.  Wolters and colleagues prospectively assembled a cohort of 358 European patients with CD who were categorized according to the Vienna classification for disease phenotype at diagnosis and were followed for at least 10 years.  Within the first 10 years of follow-up, 262 patients (73.2%) experienced a recurrence and 113 (31.6%) patients had a surgical recurrence.  Multivariate analysis identified patients with upper gastrointestinal disease to have an increased risk of recurrence. Age ≥ 40 years at diagnosis was found to protect against recurrence.  Colonic disease was associated with a decreased risk for resective surgery while more frequent surgical recurrences were reported from Copenhagen.  These results demonstrate that phenotype at diagnosis had predictive value for disease recurrence.  The increased rate of surgical recurrences observed in Copenhagen may represent a phenotypic North-South gradient.  (Wolters FL, et al. Gut 2006;55:1124-1130)

Fontolizumab dose-escalation studies.  The results of two studies of fontolizumab, a humanized anti-interferon gamma antibody, have been recently reported.  Reinisch et al conducted a double-blind, placebo-controlled study in which 45 patients with moderate to severe CD were randomized to receive single-doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) or placebo.  Patients with clinical responses were randomized a second time on day 29 to receive 3 additional doses of one half their initial fontolizumab dose or placebo at 4 weekly intervals.  Fontolizumab was generally well tolerated and patients in the 4 mg/kg fontolizumab group achieved an enhanced decrease in median CD endoscopic index of severity (p = 0.02) and serum C-reactive protein (p < 0.001) compared to placebo.  In a second study, Hommes and others randomized patients with moderate to severe CD to receive 4 or 10 mg/kg of fontolizumab or placebo.  One dose was given to 42 patients and 91 patients received 2 doses. Fontolizumab was again well-tolerated.  No difference in activity between fontolizumab and placebo were observed after one dose by day 28.  However, by day 56 after 2 doses the clinical response rate was greater in the fontolizumab 4-mg and 10-mg groups versus placebo (69% [p = 0.02], 67% [p = 0.03], and 32%, respectively).  These data indicate that fontolizumab is a safe and potentially effective therapy for patients with moderate to severe CD.  (Reinisch W, et al. Gut 2006;55:1138-1144 and Hommes DW, et al. Gut 2006;55:1131-1137)

Double-balloon endoscopy (DBE) and capsule endoscopy (CE).  Oshitani et al studied 40 patients with CD who underwent DBE and found it to be superior to radiological studies for detecting aphthae, erosions, and small ulcers in the ileum. However, one ileal perforation due to overtube balloon pressure occurred.  Thus, the overtube balloon should not be inflated if a clear intestinal view is not possible.  In a second study, Cheifetz and others retrospectively reviewed 983 CE procedures performed between 2000 and 2003 and 102 cases were identified in which CE was used in patients with suspected or known CD.  Among suspected CD cases, one (1.6%) had a retained capsule.  However, 5 (13%) patients with known CD had a retained capsule proximal to a stricture.  In 4 cases, the obstructing lesions were resected without complication.  Physicians need to be aware of the potential risk for retained capsules when using CE in patients with CD.  (Oshitani N, etal. Am J Gastroenterol 2006;101:1484-1489 and Cheifetz AS, et al. Am J Gastroenterol 2006;epub ahead of print)

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