There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis. Targeting drugs selectively to the inflamed intestine may improve therapeutic outcomes and minimize systemic toxicity. We report the development of an inflammation-targeting hydrogel (IT-hydrogel) that acts as a drug delivery system to the inflamed colon. Hydrogel microfibers were generated from ascorbyl palmitate, an amphiphile that is generally recognized as safe (GRAS) by the U.S. Food and Drug Administration. IT-hydrogel microfibers loaded with the anti-inflammatory corticosteroid dexamethasone (Dex) were stable, released drug only upon enzymatic digestion, and demonstrated preferential adhesion to inflamed epithelial surfaces in vitro and in two mouse colitis models in vivo. Dex-loaded IT-hydrogel enemas, but not free Dex enemas, administered every other day to mice with colitis resulted in a significant reduction in inflammation and were associated with lower Dex peak serum concentrations and, thus, less systemic drug exposure. Ex vivo analysis of colon tissue samples from patients with ulcerative colitis demonstrated that IT-hydrogel microfibers adhered preferentially to mucosa from inflamed lesions compared with histologically normal sites. The IT-hydrogel drug delivery platform represents a promising approach for targeted enema-based therapies in patients with colonic IBD.

Background Vitamin D has been linked to disease activity among patients with inflammatory bowel diseases (IBD). Prior investigation has also suggested that vitamin D levels may affect duration of therapy with anti-tumor necrosis factor-α (anti-TNF-α) medications among patients with IBD. Aims This study aimed to evaluate the relationship between vitamin D levels and odds of reaching remission while on an anti-TNF-α medication. Methods 521 IBD patients enrolled in the Brigham and Women’s IBD Center database were eligible for inclusion. Patients treated with anti-TNF-α therapy who had vitamin D levels drawn within 6 months prior or 2 weeks after initiation of anti-TNF-α medication and who had reported remission status at 3 months were included. A logistic regression model adjusting for age, gender, IBD diagnosis, anti-TNF-α medication (infliximab versus adalimumab) and first or subsequent anti-TNF-α medication was used to identify the effect of vitamin D level on initial response to anti-TNF-α therapy. Results 173 patients were included in the final analysis. On logistic regression, patients with normal vitamin D levels at the time of anti-TNF-α medication initiation had a 2.64 increased odds of remission at 3 months compared to patients with low vitamin D levels when controlling for age, gender, diagnosis, type of anti-TNF-α medication and first or subsequent anti-TNF-α medication (OR 2.64, 95% CI 1.31–5.32, p 0.0067). Conclusion These findings suggest that vitamin D levels may influence initial response to anti-TNF-α medication and that low vitamin D levels may predispose patients to decreased odds of remission.

Background Care of patients with inflammatory bowel disease (IBD) poses a significant burden to the health-care system. Repeat hospitalization in subgroups of IBD patients seems to be a large part of this issue; however, there are limited data examining the characteristics of these patients. The aim of this study was to characterize admission patterns in patients with IBD at a tertiary-care center and to identify preventable risk factors of 90-day readmission after an index IBD admission. Methods Retrospective analysis was performed extracting data from an electronic medical record over a 2-year period. Results Three hundred fifty-six patients were admitted at least once during the 2-year study period for an unplanned IBD-related reason. Of these, 48.9% were admitted once, 38.2% were admitted 2 to 4 times, and 12.9% were admitted 5 or more times during the study period. Patients with any admission within 90 days before index were excluded; n = 33. One hundred two patients had experienced a readmission by 90 days after index admission. Numerous demographic and medical factors were examined for association with readmission. The final Cox model included 3 variables: depression (HR = 1.99, 1.33–3.00), chronic pain (HR = 1.88, 1.14–3.10), and steroid use in the previous 6 months (HR = 1.33, 0.92–2.04). Conclusions Our findings suggest that patients with depression and chronic pain are at greatest risk for a readmission within 90 days after an initial IBD admission. Disease activity, represented by steroid use in the previous 6 months, was not related to readmission. Addressing these problems in the outpatient setting may reduce future hospitalizations.

Key findings include concordance, including some expansion, of previously published gene expression studies and similarity among different age groups. We also established a reliable statistical model for biopsy collection for future clinical studies.

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