Ankur Rustgi

Randomized, controlled trial of home telemanagement in patients with ulcerative colitis (UC HAT)

Background: Outcomes are suboptimal in ulcerative colitis (UC). Telemedicine for UC is feasible and improves outcomes. Our goals were to evaluate a home telemanagement system for UC (UC HAT) on disease activity, quality of life (QoL), and adherence compared to best available care (BAC) in a randomized, controlled trial. Methods: Adults with UC were randomly assigned to receive UC HAT or BAC for 12 months. UC HAT recruits answered questions regarding disease activity, adherence, side effects, and measured their weight weekly. An educational curriculum was delivered after each session. Alerts and action plans were generated based on the results. BAC underwent routine follow‐up, received written action plans, and were given educational fact sheets. Seo Index scores, Inflammatory Bowel Disease Questionnaire (IBDQ) scores, and adherence rates were compared between UC HAT and BAC at 1 year. Results: Twenty‐five patients were randomized to UC HAT and 22 to BAC. After 12 months, 11 withdrew in UC HAT compared to 5 in BAC. Disease activity, QoL, and adherence were not different between groups at any timepoint postbaseline. Adjusted analyses of trial completers using all available data demonstrated decreased Seo Index (11.9 in UC HAT (P = 0.08) versus 1.2 in BAC (P = 0.84) and increased IBDQ scores (12.5 in UC HAT (P = 0.04) versus to −3.8 in BAC (P = 0.47) from baseline in UC HAT compared to BAC. Conclusions: UC HAT did not improve disease activity, QoL, or adherence compared to BAC after 1 year. After adjustment for baseline disease knowledge, UC HAT trial completers experienced significant gains in disease‐specific QoL from baseline compared to BAC trial completers. Our results suggest a potential benefit of UC HAT. Further research is indicated to determine if telemedicine improves outcomes in patients with IBD. (Inflamm Bowel Dis 2012;)

Step up versus early biologic therapy for Crohn's disease in clinical practice.

Background:Recent studies have demonstrated superior outcomes of early biologic therapy. Our purpose was to evaluate differences in disease course among patients in clinical practice treated with early biologic therapy compared with those receiving conventional Step Up therapy. Methods:Patients with Crohns disease evaluated from July 2004 to November 2010 at a tertiary referral center were included. Demographic data were obtained from a prospectively maintained database. Patients were categorized into 1 of 2 groups: Early Bio group (with or without concomitant immune suppressants) or Step Up group (initial immune suppressants with or without escalation to biologic). Disease activity, quality of life, use of steroids, and number of hospitalizations, and surgeries were assessed. Results:Ninety-three patients with Crohns disease met inclusion criteria: 39 (45%) in the Step Up group and 54 (58%) in the Early Bio group. There was no significant difference in demographic and clinical variables between groups. Mean Harvey–Bradshaw index and Short Inflammatory Bowel Disease Questionnaire scores at 3, 6, and 12 months were not different between groups. Response rates were higher in the Step Up group compared with the Early Bio group only at 3 months. Early Bio patients had a greater number of hospitalizations at 1 year (P = 0.04). Conclusions:In clinical practice, early biologic therapy did not improve disease activity or quality of life and did not decrease the need for steroids or surgeries 1 year after therapy. Our results suggest that clinical outcomes are not worsened using the conventional approach. Therefore, an accelerated Step Up approach for most patients seems reasonable.

Anti-TNF therapy is associated with decreased imaging and radiation exposure in patients with Crohn's disease.

Background:Diagnostic imaging is frequently used in Crohns disease (CD) for diagnosis, evaluation of complications, and determination of response to treatment. Patients with CD are at risk for high radiation exposure in their lifetime. The aim of our study was to compare the effective dose of radiation in CD patients the year prior to and the year after initiation of anti-tumor necrosis factor (anti-TNF) agents or corticosteroids. Methods:We conducted a retrospective review of 99 CD patients initiated on anti-TNF therapy or corticosteroids between 2004 and 2009 in a tertiary care center. Results:Sixty-five patients were initiated on anti-TNF agents and 34 were initiated on corticosteroids. The anti-TNF cohort was significantly younger at diagnosis and at the time of initiation of anti-TNF or steroid therapy. The anti-TNF group had significantly more stricturing, penetrating, and perianal disease than the corticosteroid group. The anti-TNF cohort had a significant reduction in number of radiologic exams (5.5 vs. 3.7, P < 0.01) as well as a significant reduction in the cumulative radiation dose (28.1 vs. 15.0 mSv, P < 0.01) the year after initiation of therapy. This reduction was largely attributable to decreased use of computed tomography (CT) scans. In contrast, there was no significant change in radiation exposure in the corticosteroid cohort. Logistic regression analysis showed a strong trend toward higher exposure in patients with complicated disease behavior (stricturing or penetrating phenotype) (odds ratio [OR] 2.87, 95% confidence interval [CI] 0.98–8.38). Conclusions:Initiation of anti-TNF therapy for treatment of CD is associated with a significant reduction in diagnostic radiation exposure. Conversely, steroid treatment does not reduce diagnostic radiation exposure.

Differential response to microbial antigens by age of diagnosis in patients with Crohn's disease.

Purpose Fifteen percent of incident Crohn’s disease (CD) cases are diagnosed at older ages and demonstrate colonic location and inflammatory behavior. Serologic responses to gut microbial antigens are associated with specific phenotypes, and may differ by age at diagnosis. Our aim was to identify an association between age at diagnosis of CD and responses to gut microbial antigens. Patients and methods Levels of anti-Saccharomyces cerevisiae antibodies (ASCA) immunoglobulins A and G (IgA and IgG), antibodies to Escherichia coli outer membrane porin-C (anti-Omp-C), antibodies to clostridial flagellin (anti-CBir-1), and perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were compared in patients by age in three diagnosis groups: patients diagnosed at ages of <40, ≥40–59, and ≥60 years. For each antigen, patients with antibody levels in the first, second, third, and fourth quartile were assigned a score of 1, 2, 3, or 4, respectively. Individual scores were added to create a quartile sum score representing cumulative quantitative immune response. Results Eighteen, 17, and 12 patients were diagnosed at ages <40, 40–59, and ≥60 years, respectively. The majority (71%) had ileocolonic disease in the youngest group, compared to 36% in the oldest group (P=0.001). Mean ASCA IgA and IgG titers were increased in the youngest age group compared to the older groups (P=0.19 and P=0.13, respectively). Mean quartile sum scores for antibody levels were 7.2±2.8 in those patients diagnosed at ages <40 years, 4.9±2.9 in the 40–59-year-old age group, and 5.6±2.6 in the ≥60-year-old age group (P=0.06). Conclusion A trend toward decreased cumulative immune responses to CD-associated gut antigens was observed in CD patients diagnosed at older ages compared to younger patients. Host responses to microbial antigens may be less important in older onset IBD and may contribute to the distinct phenotype in this group.

P-133 Outcomes of Natalizumab Therapy in Crohnʼs Disease: Case Studies from Clinical Practice

BACKGROUND: Natalizumab, a humanized IgG4 monoclonal antibody that blocks the adhesion and subsequent migration of leukocytes into the gut by binding a 4 integrin, is FDA approved for treatment of moderate to severe Crohn’s disease. However due to the risk of progressive multifocal leukoencephalopathy (PML) associated with use of Natalizumab its use in clinical practice is limited to patients who fail the conventionally available medications specifically, one or more Anti-TNF agents. There are few publications on the use of natalizumab outside clinical trials. In this study we assessed the efficacy of Natalizumab in adults with refractory Crohn’s disease (CD) in a tertiary care center. METHODS: Retrospective case analysis of CD patients treated with Natalizumab from 2008 to 2011 at a tertiary referral center identified using an IRB-approved clinical data repository. Patients were refractory to or intolerant of conventional medical therapy including at least one anti-TNF. Natalizumab (300 mg) was infused every 4 weeks. Treatment response was assessed by physician global assessment and the Harvey Bradshaw index. Quality of life was assessed with the Short Inflammatory Bowel Disease Questionnaire. Colonoscopy or capsule endoscopy was used at the discretion of the provider to assess for mucosal healing using the Froslie Simple Endoscopic Score. RESULTS: Ten patients received treatment with Natalizumab. Mean age at diagnosis was 23.6 ± 14.1 years. Eight patients were women. Median disease duration was 13 years (range, 4–20). Nine patients had ileocolonic and 1 patient had colonic disease location; 3 had upper tract disease and 6 had perianal disease. Disease phenotype was inflammatory in 3, stricturing in 3 and penetrating in 4 patients. Five patients had extraintestinal manifestations. Median duration of Natalizumab therapy was 5 months (range, 2–36). Four patients responded, 4 patients did not respond and 2 patients experienced severe acute infusion reactions requiring discontinuation of Natalizumab. Three patients underwent follow up endoscopy; 2 had mucosal healing and one had no improvement in endoscopic activity. Six patients were tested for JC virus antibody after initiating therapy. One patient was positive but continued Natalizumab because of the excellent response to therapy. Adverse events included Varicella-zoster requiring hospitalization, recurrent vaginal Candidiasis, worsening of CD (n = 2), nasopharyngitis, and headache (n = 3). No patients developed progression multifocal leukoencephalopathy. CONCLUSIONS: In a tertiary referral center, 40% of patients experience a durable clinical response to Natalizumab. Serious infusion reactions occurred in 20% necessitating drug withdrawal and 1 patient experienced a serious opportunistic infection. The lower response rate than observed in clinical trials should be interpreted with caution given the small sample size and the treatment refractory nature of the patient population. Further research is needed to detail the experience of Natalizumab in clinical practice.

A Health Survey of Gastroenterologist Prescribing Practices with Adalimumab for Crohnʼs Disease: P-57

ied in minority populations, especially Hispanics. We developed a communitybased IBD registry for Community Regional Medical Center in Fresno, CA, the region’s safety net health system for a unique population with 50.9% of county residents identifying themselves as Hispanic. We examined potential differences in gender, IBD subtype, disease location, disease behavior, IBD related surgery, and age of diagnosis for this ethnically and socio-demographically diverse population. METHODS: A total of 1,216 possible IBD patients between years 2000 and 2010 were identified by ICD-9 codes from our medical records database. The medical records of all these patients were retrospectively reviewed to confirm diagnosis of IBD and collect epidemiologic and disease specific data. A confirmed IBD case was defined by presence of endoscopic, histologic, or radiographic evidence of IBD and treatment with an IBD-related medication or surgery. This data was analyzed to determine whether there were significant associations between race/ethnicity (Hispanics, Non-Hispanic Whites, Others) and gender, IBD subtype, disease location, disease behavior, IBD related surgery, or age of diagnosis. Chi square analysis was performed for categorical data and all p-values are two-sided. RESULTS: In this period from 2000-2010, there were 614 confirmed IBD cases: 388 ulcerative colitis (UC), 226 Crohn’s disease (CD). Hispanics comprised 39% of UC patients and 16% of CD patients. Among patients with UC, the median age of diagnosis in Hispanics was 32 years, which was significantly younger than in NonHispanic Whites with a median age of diagnosis of 38 years. In Crohn’s Disease, however, there was no significant difference in median age of diagnosis which was 31 years in Hispanics and 32 years in Non-Hispanic Whites. In Hispanics 68% of UC patients were male, whereas in Non-Hispanic Whites 47% of UC patients were male which was a significant difference (P 1⁄4 0.0001) (table 1). In contrast, for CD there were no significant associations between race/ethnicity and gender (P 1⁄4 0.33) (table 2). In addition, among the UC patients, there was no significant association between race/ethnicity and disease location (P 1⁄4 0.30), or colectomy (P 1⁄4 0.17). Among the CD patients, there were no significant associations between race/ethnicity and disease location (P 1⁄4 0.52), disease behavior (P 1⁄4 0.27) or CD related surgery (P 1⁄4 0.73). CONCLUSION(S): In Hispanics, ulcerative colitis is more predominant in males and diagnosed at a younger age than in Non-Hispanic Whites. There are racial/ethnic differences in inflammatory bowel disease and further studies in minority populations are needed.

Mo1730 Risk Factors for Vitamin D Deficiency and Impact of Repletion in a Tertiary Care Inflammatory Bowel Disease Population

Introduction Many patients with inflammatory bowel disease (IBD) are vitamin D deficient. The purpose of our study was to identify risk factors for vitamin D deficiency in IBD and to assess the impact of vitamin D repletion on disease activity and quality of life (QOL).