Identification of Risk Factors for Coexisting Sinusitis and Inflammatory Bowel Disease.

BACKGROUND: This study aimed to analyze the association of coexisting sinusitis and IBD, establish significant factors involved in their development, and enable further biological correlation between these two diseases. METHODS: The IBD and Sinusitis Study at UChicago Medicine (TISSUe) is a retrospective, single-center study. We reviewed patients to confirm IBD and chronic sinusitis diagnoses. Case-control propensity score matching was performed using matched controls with IBD only or sinusitis only. Statistical methods included Chi-squared test and Wilcoxon rank sum test. Logistic regression analysis was performed, and factors were considered significant if p<0.05. RESULTS: Stratifying 214 patients with coexisting IBD and sinusitis, 176 patients had IBD first and 38 patients had sinusitis first. Multivariable analysis of factors associated with subsequent disease with matched controls determined that duration of disease, UC, steroid exposure ever, and younger age of IBD diagnosis were associated with subsequent sinusitis in patients with IBD; steroid exposure ever and duration of sinusitis were significantly associated with subsequent IBD in patients with sinusitis. CONCLUSIONS: This study suggests that IBD maintenance therapies are not associated with increased risk of sinusitis, as proposed by adverse events in clinical trial data; rather, UC diagnosis and duration of disease may be more influential in sinusitis development. While further studies are necessary, this study also demonstrates that sinusitis precedes IBD in some patients, probing its biological association with IBD and possible classification as an extraintestinal manifestation.

Daily Aspirin Use Does Not Impact Clinical Outcomes in Patients With Inflammatory Bowel Disease.

BACKGROUND: Although several studies have associated the use of nonsteroidal anti-inflammatory drugs with disease flares in patients with inflammatory bowel disease (IBD), little is known about the impact of daily aspirin use on clinical outcomes in patients with IBD. METHODS: We conducted a retrospective analysis of a prospectively collected registry of patients with IBD from May 2008 to June 2015. Patients with any disease activity with daily aspirin use were matched 1:4 to controls by age, sex, disease, disease location, and presence of cardiac comorbidity. Patients with at least 18 months of follow-up were included in the final analysis. The primary outcomes of interest were having an IBD-related hospitalization, IBD-related surgery, and requiring corticosteroids during the follow-up period. RESULTS: A total of 764 patients with IBD were included in the analysis, of which 174 patients were taking aspirin. There was no statistical difference in age, gender, diagnosis (Crohn's disease vs ulcerative colitis), disease duration, Charlson Comorbidity Index, smoking status, medication usage, or baseline C-reactive protein between groups. After controlling for covariables and length of follow-up in the entire population, aspirin use was not associated with a risk of being hospitalized for an IBD-related complication (odds ratio [OR], 1.46; P = 0.10), corticosteroid use (OR, 0.99; P = 0.70), or having an IBD-related surgery (OR, 0.99; P = 0.96). CONCLUSION: In this single-center analysis, aspirin use did not impact major clinical outcomes in patients with IBD. Although the effect of aspirin use on mucosal inflammation was not directly assessed in this study, these findings support the safety of daily aspirin use in this population.

Real-World Experience With Proactive Therapeutic Drug Monitoring During Infliximab Reintroduction.

Background: Interruptions in infliximab therapy are associated with the development of antibodies to infliximab (ATI), infusion reactions (IRs), and loss of response. Despite these challenges, recent observational studies suggest that reinitiating infliximab after a drug holiday can be safe and effective. We assessed the utility of our protocol for restarting infliximab using early serum infliximab and ATI measurements. Methods: A retrospective cohort study of patients restarted on infliximab after at least a 6-month drug holiday. The cohort was divided into 2 groups: a "therapeutic drug monitoring (TDM) group," those who had serum infliximab and ATI measured 1-3 weeks after first reinduction dose, and a "non-TDM group." Outcomes included results of TDM, occurrence of immediate IR (IIR) and delayed hypersensitivity reactions, and medication persistence at 14 weeks and 1 year. Results: About 76 patients were included: 49 in the TDM group and 27 in the non-TDM group. Of 76, 67 (88%) patients tolerated the first reinduction dose without IR. Formation of ATI was seen in 17 of 49 (35%) patients and was associated with longer drug holidays. Most did not experience IR during the entire therapy course-in 26 of 32 (81%) without ATI and 20 of 27 (74%) in the non-TDM group. Infliximab persistence at 14 weeks and 1 year was 76% and 57% for the cohort, respectively. Conclusion: Infliximab can be safely and effectively restarted after a drug holiday. We suggest performing TDM with a drug-tolerant assay 1-3 weeks after the first reinduction infusion as a means to identify patients at risk for severe IIR at the second dose.

Impact of Angiotensin II Signaling Blockade on Clinical Outcomes in Patients with Inflammatory Bowel Disease.

BACKGROUND: Preclinical data demonstrate that activation of the renin-angiotensin system (RAS) contributes to mucosal inflammation, and RAS inhibition by angiotensin-converting-enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improves colitis in animal models. Less is known regarding the effects of RAS inhibition on clinical outcomes in inflammatory bowel disease (IBD) patients. AIM: Evaluate the impact of ACEI and ARB on clinical outcomes in IBD. METHODS: Rates of IBD-related hospitalizations, operations, and corticosteroid use were evaluated retrospectively in two groups. First, 111 IBD patients taking an ACEI or ARB were compared to nonusers matched 1:1 based on sex, age, diagnosis, disease location, and hypertension diagnosis. Second, outcomes in a cohort of 130 IBD patients were compared prior to and during ACEI/ARB exposure. RESULTS: Compared to matched controls, all IBD patients together with ACEI/ARB exposure had fewer hospitalizations (OR 0.26, p < 0.01), operations (OR 0.08, p = 0.02), and corticosteroid prescriptions (OR 0.5, p = 0.01). Comparing outcomes before and during ACEI/ARB use, there were no differences in hospitalizations, operations, or corticosteroid use for all IBD patients together, but patients with UC had increased hospitalizations (0.08 pre- vs. 0.16 during ACEI/ARB exposure, p = 0.03) and decreased corticosteroid use (0.24 pre-ACEI/ARB vs. 0.12 during ACEI/ARB exposure, p < 0.01) during ACEI/ARB use. CONCLUSIONS: IBD patients with ACEI/ARB exposure had fewer hospitalizations, operations, and corticosteroid use compared to matched controls. No differences in outcomes were observed in individuals on ACEI/ARB therapy when compared to a period of time prior to medication exposure.

Zinc Deficiency is Associated with Poor Clinical Outcomes in Patients with Inflammatory Bowel Disease.

BACKGROUND: Zinc plays a pivotal role in wound repair, tissue regeneration, and the immune response. Although zinc deficiency is common in patients with inflammatory bowel disease (IBD), the impact of low serum zinc levels on disease course is not known. METHODS: Patients enrolled in a prospectively collected IBD registry with at least 2 serum zinc measurements were included in the analysis. Using a logistic regression model, rates of IBD-related surgeries, IBD-related hospitalizations, and IBD-related complications were evaluated after a diagnosis of zinc deficiency (serum concentration <0.66 µg/mL) compared with those with normal zinc concentrations. In patients who were zinc deficient, outcomes were also analyzed between those who had normalization of zinc levels within 12 months and those who remained deficient. RESULTS: A total of 773 patients with Crohn's disease (CD) and 223 with ulcerative colitis (UC) were included in the analysis. After adjusting for covariates, zinc deficiency was associated with an increased risk of subsequent hospitalizations, surgeries, and disease-related complications in patients with CD and UC (CD: hospitalizations, odds ratio 1.44, 95% confidence interval [1.02-2.04]; surgeries, 2.05 [1.38-3.05]; complications, 1.50 [1.04-2.15]; UC: hospitalizations, 2.14 [1.07-4.29]; surgeries, 1.64 [0.59-4.52]; complications, 1.97 [0.94-4.11]). Normalization of zinc was associated with improvement in these outcomes in patients with both CD and UC. CONCLUSIONS: Patients with IBD with serum zinc deficiency are more likely to have adverse disease-specific outcomes. As these outcomes improve with normalization of zinc, the results from this study support the role for close monitoring and replacement of zinc in patients with IBD.