Budesonide induction and maintenance therapy for Crohn's disease during pregnancy.

BACKGROUND: There is no standard approach for the medical management of Crohn's disease (CD) during pregnancy and there is limited data regarding safety and efficacy of the treatments. Budesonide (Entocort EC, AstraZeneca) is an enteric coated locally acting glucocorticoid preparation whose pH- and time-dependent coating enables its release into the ileum and ascending colon for the treatment of mild to moderate Crohn's disease. There is no available data on the safety of using oral budesonide in pregnant patients. METHODS: We reviewed our Inflammatory Bowel Disease (IBD) center database to identify patients with CD who received treatment with budesonide for induction and/or maintenance of remission during pregnancy and describe the maternal and fetal outcomes in a series of eight mothers and their babies. RESULTS: The mean age of the patients was 27.7 years. All patients had small bowel involvement with their CD. The disease pattern was stricturing in 6 patients, fistulizing in 1 and inflammatory in 1 patient. Budesonide was used at the 6 mg/day dose in 6 patients and 9 mg/day dose in 2 patients. The average treatment duration ranges from 1-8 months. There were no cases of maternal adrenal suppression, glucose intolerance, ocular side effects, hypertension or fetal congenital abnormalities. CONCLUSION: Budesonide may be a safe option for treatment of CD during pregnancy.

History of medical hospitalization predicts future need for colectomy in patients with ulcerative colitis.

BACKGROUND: Patients who require hospitalization for the management of ulcerative colitis (UC) may represent a subset with severe disease. These patients may be more likely to require future colectomy. There are limited data examining whether medical hospitalization is predictive of subsequent colectomy. METHODS: This was a retrospective case-control study utilizing the inflammatory bowel disease center database at our academic referral center. Cases comprised UC patients who underwent colectomy for disease refractory to medical management. The control population was comprised of all patients with UC who had not undergone colectomy. Multivariate logistic regression was used to identify independent predictors of requiring colectomy. RESULTS: There were a total of 246 UC patients included in our study, with 103 being hospitalized sometime in their disease course (41.9%). A total of 27 patients underwent colectomy (11%). Colectomy patients were significantly more likely to have been on infliximab therapy (51.8% versus 22.4%, P = 0.001) but no more likely to have been on immunomodulator therapy (74.1% versus 59.4%, P = 0.14). Patients who required medical hospitalization for UC were more likely to require future colectomy (20.4% versus 4.2%, P < 0.001) than those who had not required hospitalization. On multivariate analysis, requiring medical hospitalization for management of UC (odds ratio [OR] 5.37, 95% confidence interval [CI] 2.00-14.46) and ever requiring infliximab therapy (OR 3.12, 95% CI 1.21-8.07) were independent predictors of colectomy. CONCLUSIONS: Requiring medical hospitalization for the management of disease activity in UC is an independent predictor of the need for colectomy. Future studies will determine whether aggressive medical management may modify the need for colectomy in this cohort.

Permanent work disability in Crohn's disease.

OBJECTIVE: Crohn's disease (CD) frequently presents during early adulthood, a peak time of work productivity. There are limited data from the United States on work disability from CD. We performed this study to identify clinical factors associated with permanent work disability in a CD tertiary referral cohort. METHODS: Cases were identified as patients who received permanent work disability compensation from the social security administration (SSA) related to CD. Four control patients who were not receiving work disability were selected for each case. Multivariate logistic regression was performed to identify characteristics that were independently associated with work disability. RESULTS: A total of 737 patients with CD were seen in our center, and 185 CD patients were included in our study (37 disability cases, 148 controls). On multivariate analysis, an SIBDQ score

Impact of Clostridium difficile on inflammatory bowel disease.

BACKGROUND & AIMS: Clostridium difficile-associated disease has increased significantly in North American medical centers. The impact of C difficile on patients with IBD (Crohn's disease, ulcerative colitis) at the present time is unknown. METHODS: A retrospective, observational study evaluating IBD patients followed in a referral center to evaluate the impact of C difficile was performed. Diagnosis was confirmed with stool toxin analysis. Demographic information, diagnosis, anatomic location, IBD therapy, antibiotic exposure, hospitalizations, and surgeries were recorded. Available endoscopic and histologic data were evaluated. RESULTS: Rate of C difficile infection increased from 1.8% of IBD patients in 2004 to 4.6% in 2005 (P < .01). Proportion of IBD patients within the total number of C difficile infections at our institution increased from 7% in 2004 to 16% in 2005 (P < .01). IBD colonic involvement was found in the majority of C difficile-infected patients in 2005 (91%), and the majority contracted infection as an outpatient (76%). Antibiotic exposure was identified in 61% of IBD patients with C difficile infection in 2005. Pseudomembranes and fibrinopurulent eruptions were not seen endoscopically or histologically. During 2004-2005 more than half of the infected IBD patients required hospitalization, and 20% required colectomy. Univariate and multivariate analysis identified maintenance immunomodulator use and colonic involvement as independent risk factors for C difficile infection in IBD. CONCLUSIONS: C difficile infection has increased significantly in IBD patients and negatively impacts clinical outcome. Increased vigilance regarding this infection in IBD patients with colitis activity is warranted.

Increased rates of early adverse reaction to azathioprine in patients with Crohn's disease compared to autoimmune hepatitis: a tertiary referral center experience.

OBJECTIVES: Idiosyncratic drug hypersensitivity may occur at increased rates in specific patient populations. Azathioprine has a significant early adverse reaction (EAR) profile, which includes an acute syndrome of constitutional symptoms, fever, rash, and acute pancreatitis and often requires discontinuation of drug. EAR precludes azathioprine use in patients with Crohn's disease (CD) and autoimmune hepatitis (AIH). Our aims were to investigate differential rates of EAR to azathioprine in CD compared to AIH in a tertiary referral center population. METHODS: Retrospective chart review of consecutive CD and AIH patients who were initiated on azathioprine in our inflammatory bowel disease (IBD) and hepatology centers was performed. EAR (fevers and constitutional symptoms, severe arthralgias, nausea, and vomiting) were defined as those occurring within 1 month of initiation. EAR rates between AIH and CD patients were compared using the Fisher's exact test. RESULTS: One hundred and forty-three CD (88F/55M; age 39.2 +/- 13 yr) and 40 AIH (35F/5M; age 53.1 +/- 14 yr) patients were studied. All patients were initiated with equivalent azathioprine dosage (50 mg qd). All AIH patients were on prednisone (mean daily dose 7.5 mg) compared to 51% of CD patients (median daily dose 20 mg). EAR rates were significantly higher in CD patients (42/143; 29%) compared to AIH (2/40; 5%) (Fisher's exact test; p= 0.008). EAR excluding nausea and vomiting were still significantly higher in CD patients (27/143; 19%) compared to AIH (1/40; 2.5%) (Fisher's exact test; p= 0.01). All patients with EAR required drug discontinuation and 7% of CD patients required hospitalization for management of these complications. CONCLUSIONS: CD patients represent a unique subgroup at increased risk of EAR to azathioprine. Mechanisms behind these reactions need to be further defined.

Leflunomide treatment of Crohn's disease patients intolerant to standard immunomodulator therapy.

BACKGROUND: Immunomodulator therapy with the purine analogs azathioprine and 6-mercaptopurine (6-MP), is efficacious in the treatment of moderate to severe Crohn's disease (CD), but is not tolerated by a significant minority of patients. The pyrimidine analog, leflunomide, has demonstrated efficacy in the treatment of rheumatoid arthritis (RA) patients. Because established RA immunomodulator agents may demonstrate success in the treatment of CD, we reviewed our clinical open-label experience with leflunomide in a refractory CD population. GOALS Assess the effect of leflunomide 20 mg daily, on disease activity, steroid requirement and serologic measures of inflammatory activity in our series of CD patients intolerant to azathioprine/6-MP. STUDY: CD patients intolerant of azathioprine/6-MP were offered leflunomide treatment. The Harvey-Bradshaw (H-B) disease activity index, global assessment, serologic parameters and ability to taper corticosteroids of those who accepted were retrospectively assessed. RESULTS: Leflunomide was well tolerated and resulted in a significant reduction in the H-B score, global assessment and serologic parameters in 8/12 patients. Average follow-up was 38 weeks and a majority of steroid-dependent patients were able to successfully taper following leflunomide initiation. CONCLUSIONS: Our case series demonstrates that the pyrimidine analog leflunomide may be effective for treating moderate to severe CD patients intolerant to standard immunomodulator therapy and warrants further investigation in a randomized controlled trial.

Infliximab retreatment in adults and children with Crohn's disease: risk factors for the development of delayed severe systemic reaction.

OBJECTIVES: Although effective in the treatment of refractory Crohn's disease, episodic retreatment with the antitumor necrosis factor a chimeric monoclonal antibody infliximab (Remicade, Centocor, Malvern, PA) can be associated with severe acute and delayed systemic reactions. METHODS: We analyzed episodic infliximab retreatment over 30 months in 86 adult and pediatric patients receiving 304 infusions to determine factors associated with the development of severe systemic reaction. RESULTS: Overall, 14% of patients experienced severe systemic reactions with episodic infliximab retreatment. There was a significant difference in the rates of severe systemic reaction observed in adults (11/52 [21%]) and pediatric patients (1/34 [3%]) (p < 0.02). Delayed systemic reactions, characterized by arthralgia, fever, and myalgia requiring corticosteroid treatment, were found exclusively in adults (age > 17 yr) and occurred in eight patients treated for luminal Crohn's disease. Acute systemic reactions, characterized by hypotension, mucosal irritability, and laryngospasm requiring epinephrine, diphenhydramine, and/or methylprednisolone treatment, occurred sporadically in three adults and one child, treated for both luminal and fistulizing disease. Second infliximab infusions were associated with two thirds of severe systemic reactions, and a distant second infusion (> or = 20 wk from first infusion) was poorly tolerated relative to earlier retreatment (p < 0.001). Concomitant medications were similar in adults and children. CONCLUSIONS: Episodic infliximab retreatment--specifically, a distant second infusion--is associated with high rates of severe systemic reaction in adults, but not children. We recommend multiple early infusions of infliximab if retreatment is anticipated in adult patients to avoid the development of delayed severe systemic reactions.

Successful treatment of an acute flare of steroid-resistant Crohn's colitis during pregnancy with unfractionated heparin.

Recent reports suggest that unfractionated heparin may be a useful adjunct in the treatment of inflammatory bowel disease (IBD). We report the successful use of subcutaneous unfractionated heparin to treat a moderate-to-severe flare of Crohn's disease during pregnancy, which was refractory to standard therapy. The patient received 10,000 units of unfractionated heparin subcutaneously twice a day after her Crohn's colitis failed to come under remission with intravenous corticosteroids. Heparin was continued throughout her pregnancy. Following initiation of adjunctive heparin therapy, the patient experienced a rapid clinical response, was able to discontinue intravenous steroids, discharge from the hospital, and ultimately deliver a healthy term newborn. Although there is extensive obstetric experience with heparin in the treatment of thrombosis associated with pregnancy, there is limited information regarding its use in IBD patients during pregnancy. Because heparin has an established track record in maternal-fetal medicine, this agent may be considered in women who suffer an inflammatory flare of IBD during pregnancy who have not responded to standard treatment.