Crohn Disease

Long-Term Benefits and Risks of Methotrexate in Crohn Disease.

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In patients previously treated with thiopurine, risk for adverse reaction was low with methotrexate monotherapy, but so was the rate of sustained response.

In treating patients with Crohn disease, clinicians typically use anti–tumor necrosis factor (anti-TNF) agents and the immunomodulatory agents azathioprine and 6-mercaptopurine before methotrexate. Gastroenterologists tend to be concerned about the long-term risks of methotrexate, including liver fibrosis, although recent studies suggest that the risk for cirrhosis is considerably lower than previously thought. Now, investigators have retrospectively assessed the long-term response and safety of methotrexate for Crohn disease.

The study cohort of 174 patients (mean age, 35 years; median disease duration, 4 years) received intramuscular methotrexate monotherapy following thiopurine therapy, with 23% also having received but not responded to anti-TNF therapy. Patients received 25 mg of methotrexate weekly, eventually tapering to 15 mg. The most common indication was intolerance of a thiopurine (55%), followed by clinical failure of thiopurines (24%), failure of anti-TNF monotherapy (9%), and failure of combination anti-TNF agents and thiopurines (12%). A sustained clinical benefit was defined as ongoing use of methotrexate or intentional discontinuation of successful therapy (e.g., in anticipation of pregnancy) prior to the end of study.

Patients intolerant of thiopurine were more often intolerant of methotrexate than were patients in whom methotrexate was initiated for thiopurine failure (22 vs. 6). The rate of sustained clinical benefit of monotherapy methotrexate was 86% at 6 months; 63% at 12 months; 47% at 24 months; and 20% at 60 months. The most common reasons for discontinuation were adverse reaction (56%; most frequently GI complaints and general malaise, including fatigue, fever, dizziness, and headache); loss of response (38%); and primary nonresponse (5%). No liver biopsies were taken, and only 6% of discontinuations were for asymptomatic increases in liver enzymes.

Comment: This study indicates that when used in patients with thiopurine failure in Crohn disease, methotrexate has a low risk for adverse reactions, but also a relatively low long-term sustained response rate.

 

Source: Journal Watch Gastroenterology

Successful treatment with azathioprine of relapsing Rosai-Dorfman disease of the central nervous system.

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Rosai-Dorfman disease (RDD) is a rare non-Langerhans histiocytosis that usually presents with lymphadenopathy. Although isolated involvement of the CNS was considered to be uncommon, numerous cases have been reported in recent years. For RDD of the CNS, the treatment consists, in general, of surgery. In cases of partial resection or relapse, chemotherapy regimens, corticosteroids, and/or radiotherapy have yielded negative results. The authors describe the case of a 57-year-old man with a history of chronic Q fever who presented with aphasia and partial seizure. Computed tomography of the brain revealed a left frontotemporal lesion that was suggestive of a meningioma. The lesion was partially resected and histopathological evaluation revealed the presence of RDD. Nineteen months later, a Jacksonian seizure prompted MRI evaluation, which disclosed a local recurrence of the tumor. Computed tomography and FDG-PET demonstrated that the RDD involved no other site, but the presence of ileitis, noted on ileoscopy, led to the diagnosis of Crohn disease. Treatment with the purine analog azathioprine was initiated, leading to an objective and sustained response in both the RDD tumor and ileitis over 35 months of follow-up. This case report highlights the potential use of a purine analog in cases of relapsing RDD of the CNS and a possible common defect of macrophage regulation in RDD, Crohn disease, and Q fever.

Source: Journal Of Neurosurgery.

 

 

Rifaximin Efficacious in Moderately Active Crohn Disease.

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Twelve weeks of extended-release rifaximin at 800 mg twice daily induced remission in 62% of patients and was both safe and well tolerated.

Many clinicians use antibiotics to treat infection in patients with Crohn disease; some also use them to suppress disease activity, despite mixed evidence to support their efficacy for this purpose. Now, researchers in Europe have conducted a multicenter, double-blind, phase II trial to determine whether an extended intestinal release (EIR) form of rifaximin induces remission in patients with moderately active Crohn disease.

In this manufacturer-funded study, participants (410 adults with Crohn’s Disease Activity Index scores between 220 and 400) were randomized to receive twice-daily rifaximin-EIR (400 mg, 800 mg, or 1200 mg) or placebo for 12 weeks. Patients in remission at the end of the treatment period were followed for an additional 12 weeks. A total of 402 patients received at least one dose of study drug and were included in the full analysis.

At the end of treatment, the remission rate was higher in the 800-mg rifaximin group than in the placebo group (62% vs. 43%; P=0.005). The difference was maintained throughout the follow-up period (at 24 weeks, 45% vs. 29%; P=0.02). Remission rates were 54% in the 400-mg group and 47% in the 1200-mg group and were not significantly different from the placebo group rate. Dropout because of adverse events was significantly more common in the 1200-mg group than in any of the other groups.

Comment: These results support a role for bacteria in the pathogenesis of Crohn disease. The extended-release formulation of rifaximin used in this trial is not yet available in the U.S.

Source: Journal Watch Gastroenterology