Josh F. Knox

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

Background: There is no standard approach for the medical management of Crohns 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 Crohns 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.

Permanent Work Disability in Crohn's Disease

OBJECTIVE:Crohns 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 ≤50 (OR 12.44, 95% CI 4.45–34.79), undergoing two or more GI surgeries (OR 7.09, 95% CI 2.63–19.11), and two or more medical hospitalizations (OR 2.76, 95% CI 1.03–7.37) were significantly associated with work disability in CD. Disease location (small bowel vs colon), type (inflammatory, stricturing, or fistulizing), or specific treatment strategies were not associated with work disability in our analysis.CONCLUSION:Permanent work disability administered through social security was encountered in 5.3% of the Crohns patients followed in our cohort. Patients who consistently report low quality of life, or have frequent flares requiring surgical intervention or hospitalization for medical management, may be at risk for CD-related work disability.

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.

Suppressive anti-HCV therapy for prevention of donor to recipient transmission in stem cell transplantation

A 48-yr-old man with acute myeloid leukemia (AML) required urgent allogeneic hematopoietic stem cell transplantation because of failed attempts to induce remission via chemotherapy. He had an HLA identical donor sister who was hepatitis C virus (HCV) RNA positive. In order to prevent HCV transmission to her brother, the donor was treated with weekly injections of pegylated interferon alfa-2b (150 μg subcutaneously every week) and daily ribavirin (1 g/day) for 5 wk at which time her qualitative polymerase chain reaction (PCR) was negative. Her stem cells were successfully grafted into the recipient. The recipient remained HCV PCR negative after transplant until death from relapsed AML.

Impact of prior irregular infliximab dosing on performance of long-term infliximab maintenance therapy in Crohn's disease†

Background: Infliximab is efficacious in the management of moderate to severe Crohns disease (CD). There are limited data regarding performance of infliximab in patients who require reinitiation of maintenance dosing following previous irregular exposure. Methods: This was a retrospective, observational study of CD patients treated with maintenance infliximab beyond 3 years. Maintenance infliximab infusion regimens were categorized as scheduled maintenance (SM) (maintenance infusions q ≤8 weeks after loading) or prior irregular (PI) (no loading, gap in therapy >8 weeks prior to or during maintenance therapy). We examined differences in need for medical and surgical hospitalizations as well as associated healthcare costs between the 2 groups. Results: In all, 104 CD patients met criteria for 3‐year maintenance infliximab treatment (SM n = 64; PI n = 40). The rates of CD‐related surgeries (60.9% and 55.0%, P = not significant [N.S.]) and medical hospitalizations (35.9% and 37.5%, P = N.S.) prior to infliximab initiation was similar between the 2 groups. However, the rate of medical (26.5% versus 47.5%, P = 0.035) and surgical hospitalizations (21.8% versus 48.7%, P = 0.009) were significantly lower in the SM compared to the PI group. During the third year of treatment the excess costs per patient for the PI group compared to the SM group amounted to

Increased rates of drug allergy in inflammatory bowel disease (IBD) patients compared to irritable bowel syndrome (IBS) patients and normal controls

11,464 in spite of both cohorts being on SM therapy. Conclusions: Patients who begin and continue an uninterrupted maintenance dosing regimen had a lower incidence of hospitalization and surgery than those who received an irregular or interrupted regimen prior to beginning an SM regimen. (Inflamm Bowel Dis 2010)

Impact of Clostridium difficile on Inflammatory Bowel Disease

Background and Aims: Drug allergy (rash, angioedema, anaphylactic, anaphylactoid reactions) is a frequently encountered clinical problem, and published reports suggest that it is present in up to 20% of hospitalized patients. The rate of drug allergy among patients with 1BD (Crohns disease (CD), ulcerative colitis (UC)) has not been previously described. We hypothesized that adult patients with chronic gut inflammation would have increased rates of drug allergy compared to controls. Methods: Retrospective observational analysis was performed on all 1BD patients followed at a tertiary referral center. All intake visits were reviewed for histories of drug allergy, defined as emergence of rash, angnoedema, anaphytactic/ anaphylactoid reaction following challenge with the offending agent. Demographic information regarding patients as well as classes of agents inducing allergic reactions were recorded, as was the duration of the IBD. Controls included patients with irritable bowel syndrome as well as healthy volunteers without clinical evidence of gastrointestinal disease. Results: Records of 410 IBD patients (297 CD, 107 UC, 6 indeterminate colitis) were reviewed, as weft as 230 control patients (IBS 50, normal 180). 33.2% of IBD patients and 19% of controls demonstrated drug allergy ( p = < 0.001 Chi-square). There was no difference between the prevalence of drug allergy between CD and UC patients. The duration of disease did not impact on the prevalence of drug allergy. There were significantly more female IBD patients with drug allergy when compared to males (36% vs. 25%; p = < 0 . 0 3 ) which corresponded with an increased rate of drug allergy noted in the female control population. The classes of drugs associated with allergic reactions in IBD patients included penicillin (13.9%), sulfa (8.3%), narcotics (7.1%). The prevalence of antibiotic allergy in the IBD patients was 22% compared with 11% of controls (p = <O.001). Conclusions: The prevalence of drag allergy is significantly higher in patients with IBD compared to patients with IBS or healthy volunteers. Female IBD patients have a higher prevalence of allergic reactions compared to males, but there is no difference in the prevalence of the reactions between UC and CD Drug allergnc IBD patients are a commonly encountered phenotype which pose added clinical challenges in management.