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). METHODS: Patients with at least one 25-OH vitamin D level measured between 2004 and 2011 were included. Patients with a level <30 ng/ml at baseline were followed until the time of repletion. QOL and disease activity scores were measured at baseline and repletion. RESULTS: A total of 255 patients were identified. 33, 29, and 39% had a vitamin D level of ≥30, 20-29, and <20 ng/ml, respectively. When adjusting for disease type and duration, gender, smoking, and race, non-Caucasians had 5.3 (2.3-12.3) and UC patients had a 0.59 (0.33-1.03) odds of having a vitamin D <30 ng/ml. Women were 1.7 times more likely to have a 25-OH vitamin D level <20 ng/ml than men. 55 patients underwent repletion. In CD patients, the HBI and SIBDQ prior to repletion was 5.5 ± 4.9 and 44.3 ± 16.4, respectively; these improved to 3.6 ± 3.4 and 48.6 ± 14.2 after repletion (p = 0.0154 and p = 0.0684). CONCLUSIONS: In this tertiary care IBD cohort, the majority of patients have low vitamin D levels. Non-Caucasian race and female gender are associated with low vitamin D. UC was associated with lower risk of vitamin D insufficiency. In CD, vitamin D repletion is associated with decreased disease activity and increased QOL.

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.

Racial differences in disease activity and quality of life in patients with Crohn's disease.

BACKGROUND: The existing literature on racial differences in Crohn's disease (CD) activity and quality of life (QOL) is limited and extrapolated from surrogate measures. AIM: The aim of our study was to compare objective markers of disease activity and QOL over time by race. STUDY: A clinical data repository of inflammatory bowel disease (IBD) patients at University of Maryland, Baltimore IBD Program, was used. CD patients from 2004 to 2009 were included if they had greater than or equal to two clinic visits with disease activity and QOL scores during the study period. Differences in disease activity and QOL were compared by race over time. RESULTS: A total of 296 patients with CD met inclusion criteria; of these, 19% (56/296) were African Americans (AA) and 81% (240/296) were Caucasian. Baseline disease activity and QOL scores did not differ by race (p > 0.05). Caucasians had a steady decline in disease activity and increase in QOL. AA experienced a similar pattern of change in disease activity and QOL scores over time; however, the declines were not statistically significant between groups. At each time point post-baseline, disease activity and QOL scores were similar between races. CONCLUSION: We found that Caucasian and AA patients with CD had similar disease activity and QOL scores at initial presentation and over time. Thus, AA do not represent a more severe subgroup of CD patients to treat. These findings have important implications for clinicians that care for patients with CD.

A Health Survey of Gastroenterologist Prescribing Practices of Adalimumab for Treatment of Crohn's Disease: Final Results.

Adalimumab (Humira, AbbVie) has efficacy in treatment-naive and infliximab (Remicade, Janssen)-exposed patients with Crohn's disease (CD). An e-survey was sent to US gastroenterologists who were members of the American Gastroenterological Association. A total of 398 gastroenterologists (3%) completed the survey. Seventy-two percent prescribed adalimumab more than a few times yearly, 58% followed more than 50 patients with CD, and 15% followed 200 or more patients with CD. Ninety percent of gastroenterologists felt that adalimumab had a moderately significant positive impact on patient care. Eighty-two percent correctly identified the US Food and Drug Administration-approved adalimumab induction and maintenance regimens. These gastroenterologists were more likely to follow 200 or more patients with CD (P=.045) and prescribe adalimumab more than a few times per year (P=.037). Years in practice, practice setting, gender, and region did not impact prescribing. Correct dosing was associated with higher prescribing frequency (P=.014) and volume of patients with CD (P=.025). The frequency of adalimumab prescribing and volume of patients with CD were predictive of the total number of correct survey answers (P=.014 and P=.017, respectively). Only 50% of gastroenterologists always administered loading doses when switching to adalimumab from another anti-tumor necrosis factor (TNF) agent; 43.5% reported unclear loading efficacy and 24.3% reported infection concerns from excess anti-TNF as reasons. Eighteen percent of gastroenterologists reported that pharmacies had reduced their prescribed adalimumab doses. To our knowledge, this is the only study evaluating prescribing patterns of adalimumab in patients with CD in the United States. Our findings demonstrate that many gastroenterologists are not using optimal adalimumab dosing strategies, which may lead to a decreased rate of response in patients with CD. Further research is needed to confirm our findings and identify barriers to optimal adalimumab use by gastroenterologists for treatment of CD.

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 Crohn's 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 Crohn's 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 Crohn's 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.

Comparative effectiveness of anti-TNF agents for Crohn's disease in a tertiary referral IBD practice.

BACKGROUND: The three Food and Drug Administration (FDA)-approved anti-tumor necrosis factor drugs (anti-TNFs) for Crohn's disease (CD) have not been directly compared. AIM: To compare the efficacy of the three anti-TNFs for CD in clinical practice. METHODS: Retrospective review of patients initiated on anti-TNF between 2004 and 2008. Disease activity, quality of life, and remission rates were compared between groups over 1 year. RESULTS: Sixty patients with CD were initiated on anti-TNF from 2004 to 2008: 31 on infliximab (IFX) and 29 on adalimumab (ADA) or certolizumab pegol (CTZ). More patients in the ADA/CTZ scores group had prior exposure to anti-TNF (76 versus 10%, p < 0.01). Mean Harvey-Bradshaw Index (HBI) scores in the IFX group were lower than in the ADA/CTZ group at 12 months (2.72 ± 3.34 versus 5.63 ± 5.33, p = 0.03). At 12 months, more IFX patients were in remission compared with those on ADA/CTZ (88 versus 53%, p ≤ 0.01). Mean short inflammatory bowel disease questionnaire (SIBDQ) scores were not different between the IFX and ADA/CTZ groups at 12 months. Stratified analyses and logistic regression based on prior anti-TNF use did not show differences in remission rates at any time point post-baseline between groups. CONCLUSIONS: After adjustment for prior anti-TNF there was no difference in remission rates between the IFX and ADA/CTZ groups at any time point post-baseline. This suggests that differences between groups were accounted for by a higher rate of prior anti-TNF in the ADA/CTZ group. Our results should be reviewed with caution given the small sample size.

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.