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MAY
2005
CROHN'S DISEASE (CD)
Autologous hematopoietic stem cell transplantation (HSCT). HSCT may
induce remissions in CD, an immunologically mediated inflammatory disease, by
immune ablation. Yu Oyama and colleagues conducted a phase I study in which 12
patients with CD refractory to conventional therapies, including infliximab,
were treated with high-dose cyclophosphamide (200 mg/kg) and antithymocyte
globulin (90 mg/kg), followed by HSCT rescue. All patients were <60 years of age
and had a CD Activity Index (CDAI) of 250 to 400. Peripheral blood stem cells
were mobilized for harvest with cyclophosphamide and granulocyte
colony-stimulating factor. The procedure was tolerated well; median times to
neutrophil and platelet recovery were, respectively, 9.5 days (range, 8–11 days)
and 9 days (range, 9–18 days). Of the 12 patients, 11 achieved a sustained
remission (CDAI ≤150). After a median follow-up of 18.5 months (range, 7–37
months), only 1 patient had recurrence of CD (15 months after HSCT). These
preliminary findings are encouraging, considering that this is a potentially
toxic therapy (including death) that yields only short-term results. Unknown is
whether it is the bone marrow transplant or the cytotoxic therapy that is
inducing the results. (Oyama Y, et al. Gastroenterology.
2005;128:552–563)
Ornidazole prophylaxis. Paul Rutgeerts and colleagues performed a
double-blind, placebo-controlled trial in which 80 patients with CD were
randomized to receive oral prophylactic treatment with the nitroimidazole
antibiotic ornidazole (1 g/day) or placebo for 1 year following ileocolonic
resection. The clinical recurrence rate at 1 year was only 7.9% for
ornidazole-treated patients vs 37.5% for placebo patients (P=0.0046). Ornidazole
therapy was also associated with a reduced rate of endoscopic recurrence at 1
year (53.6% vs 79%; P=0.037). Although ornidazole was effective at reducing
clinical recurrence, 12 of 38 patients discontinued treatment because of side
effects (primarily metallic taste, nausea, vomiting, or neuropathy). Ultimately,
a better-tolerated regimen will be needed, and results will need to be compared
against postoperative therapy using mercaptopurine. (Rutgeerts P, et al.
Gastroenterology. 2005;128:856–861)
ULCERATIVE COLITIS (UC)
Trichuris suis therapy. In animal models, infection with helminths prevents
or improves colitis through the induction of regulatory T cells and modulatory
cytokines. These findings led Robert Summers and associates to conduct a
double-blind, placebo-controlled study in which 54 patients with active UC (UC
Disease Activity Index ≥ 4) were randomized to receive helminth (Trichuris suis)
ova (n = 30) or placebo (n = 24) orally at 2-week intervals for 12 weeks. The
study treatments were tolerated without side effects. After 12 weeks of therapy,
improvement in the Disease Activity Index occurred in 13 of the helminth-treated
patients (43.3%), compared with 4 of the placebo patients (16.7%) (P= 0.04).
Lloyd Mayer critically analyzed these data in an accompanying editorial. He
questioned the proposed mechanism of action of helminth therapy in UC and
whether the clinical endpoints of this study are clinically relevant. Further
research is warranted to investigate clinical remissions and maintenance therapy
with helminth ova in patients with UC. (Summers RW, et al. Gastroenterology.
2005;128:825–832; Mayer L. Gastroenterology. 2005;128:1117–1119)
The clinical course of distal UC. Jeong-Sik Byeon et al evaluated the
clinical significance of appendiceal orifice inflammation (AOI) in patients with
UC by prospectively analyzing colonoscopic findings of 94 Korean patients with
newly diagnosed distal UC treated from March 1996 to October 2002. Among these
94 patients, 48 were found to be AOI positive and 46 were AOI negative. Clinical
remission was achieved in all patients in both groups. There were no differences
in relapse rates or risk of proximal disease extension between the groups. These
data indicate that AOI is not a prognostic risk factor in patients with distal
UC. (Byeon J-S, et al. Inflamm Bowel Dis. 2005;11:366–371)
INFLAMMATORY BOWEL DISEASE (IBD)
Monitoring of 6-thioguanine in patients receiving azathioprine.
6-Thioguanine is an active metabolite of azathioprine. Xavier Roblin and
colleagues attempted to titrate the dose of azathioprine in 106 patients with
steroid-dependent IBD (70 patients with CD and 36 patients with UC) so that a
6-thioguanine level of >250 pmol/8 108 red blood cells (RBCs) could be
achieved. The clinical remission rate without steroids was 72% and 59% at 6 and
12 months of treatment, respectively. The remission rate was greater in the
patients in whom a 6-thioguanine level >250 pmol/8 108 RBCs was attained (86%
and 69% at 6 and 12 months, respectively; P<0.01). Multivariate analysis
identified only 6-thioguanine level to be predictive of a clinical remission.
These results demonstrated that monitoring 6-thioguanine levels may optimize
azathioprine therapy for patients with IBD. (Roblin X, et al. Aliment
Pharmacol Ther. 2005;21:829–839)
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