Satimai Aniwan

Antibiotic Use and New-Onset Inflammatory Bowel Disease in Olmsted County, Minnesota: A Population-Based Case-Control Study

Background and AimsnSeveral studies have suggested significant associations between environmental factors and the risk of developing inflammatory bowel disease [IBD]. However, data supporting the role of antibiotics are conflicting. The aim of this study was to evaluate the association between antibiotic use and new-onset IBD.nnnMethodsnWe conducted a population-based case-control study using the Rochester Epidemiology Project of Olmsted County, Minnesota. We identified 736 county residents diagnosed with IBD between 1980 and 2010 who were matched to 1472 controls, based on age, sex and date of IBD diagnosis. Data on antibiotic use between 3 months and 5 years before IBD diagnosis were collected. Logistic regression models were used to estimate associations between antibiotic use and IBD, and were expressed as adjusted odds ratio [AOR] with 95% confidence interval [CI].nnnResultsnAntibiotic use occurred in 455 IBD cases [61.8%] and 495 controls [33.6%] [p < 0.001]. In multivariate analysis, there were statistically significant associations between antibiotic use and new-onset IBD [AOR, 2.93; 95% CI, 2.40-3.58], Crohns disease [CD] [AOR, 3.01; 2.27-4.00] and ulcerative colitis [UC] [AOR, 2.94; 95% CI, 2.23-3.88]. A cumulative duration of antibiotic use ≥ 30 days had the strongest AOR [6.01; 95% CI, 4.34-8.45]. AOR for those receiving antibiotics under the age of 18 years was 4.27 [95% CI, 2.39-7.91], 2.97 for age 18-60 years [2.36-3.75] and 2.72 for age > 60 years [1.60-4.67].nnnConclusionsnThis population-based case-control study suggests a strong association between antibiotic use and the risk of both new-onset CD and new-onset UC. The risk was increased among all age-onset IBD.

Epidemiology, Natural History, and Risk Stratification of Crohn's Disease

Crohns disease (CD) is a chronic condition that can result in significant morbidity and disability. By studying the association between demographics and initial clinical features and subsequent natural history, one may be able to stratify patients by their risks of clinical relapse, hospitalization, and surgery. Understanding the potential environmental risk factors and natural history of CD in a given patient guides the physician when counseling the patient and selecting a treatment strategy. In this review, updated data regarding the incidence and prevalence of CD, important environmental risk factors, natural history of the disease, and important prognostic factors are discussed.

Advances in the use of biologics and other novel drugs for managing inflammatory bowel disease

For the ultimate aim of preventing intestinal disability in inflammatory bowel disease (IBD), the treatment goal has moved from symptom control towards inflammation control (i.e., deep remission). Furthermore, the concept of treat-to-target has been adopted to assist in treatment escalation and better control. Although deep remission is possible with current biologics, there are still unmet needs in IBD management. Biosimilars of several biologics will be an increasingly common option in the near future. In this review, we review the current status of novel drugs for IBD, focusing on recent phase 2 and 3 randomized controlled trials, and address the issues of biosimilars. Recent studies of the treat-to-target strategy and therapeutic drug monitoring are summarized.

Overall and Cause-Specific Mortality of Inflammatory Bowel Disease in Olmsted County, Minnesota, From 1970 Through 2016

Objective: To determine the mortality of Crohn disease (CD) and ulcerative colitis (UC) and temporal trends in mortality. Patients and Methods: All 895 residents of Olmsted County, Minnesota, first diagnosed as having inflammatory bowel disease (IBD) (411 with CD and 484 with UC) from January 1, 1970, through December 31, 2010, were followed through June 30, 2016. Standardized mortality ratios (SMRs) were computed—expected rates were derived from the US 2010 background population. To determine overall and cause‐specific mortality, each patient with IBD was matched with 5 county residents, and Cox regression analysis was used to assess time to death. Results: A total of 895 patients with IBD and 4475 patients without IBD were included. Seventy‐four patients with CD died compared with 59.2 expected (SMR, 1.25; 95% CI, 0.98‐1.57), and 77 patients with UC died compared with 108.1 expected (SMR, 0.71; 95% CI, 0.56‐0.89). In CD, the risk of dying was significantly associated with diagnosis from 1970 through 1979 (SMR, 1.90; 95% CI, 1.24‐2.78). Of those diagnosed after 1980, the risk of dying in patients with CD was similar to the US background population. In UC, the risk of dying was less than expected in all periods of diagnosis. In the Cox regression analysis, overall mortality was not significantly higher in CD (hazard ratio [HR], 1.26; 95% CI, 0.97‐1.63) or UC (HR, 0.89; 95% CI, 0.70‐1.14) compared with the comparison cohort. The risk of dying of digestive diseases (HR, 3.70; 95% CI, 1.24‐11.0) and respiratory diseases (HR, 2.72; 95% CI, 1.36‐5.44) was increased in CD but not UC. Conclusion: In this cohort, overall mortality in patients with CD diagnosed after 1980 did not differ from that in the US background population. Overall mortality in patients with UC diagnosed from 1970 through 2010 was lower than the expected mortality.

Update on the Natural Course of Fistulizing Perianal Crohn’s Disease in a Population-Based Cohort

BACKGROUNDnThis study sought to re-estimate the cumulative incidence of perianal or rectovaginal fistulas and the associated proctectomy rate in the prebiologic era vs the biologic era using a population-based cohort of Crohns disease (CD) patients.nnnMETHODSnThe medical records of 414 residents of Olmsted County, Minnesota, who were diagnosed with CD between 1970 and 2010 were reviewed. The cumulative incidence of perianal or rectovaginal fistulas from time of CD diagnosis and the cumulative rate of proctectomy from date of first perianal or rectovaginal fistula diagnosis were estimated using the Kaplan-Meier method.nnnRESULTSnEighty-five patients (20.5%) diagnosed with CD between 1970 and 2010 had at least 1 perianal or rectovaginal fistula episode between January 1, 1970, and June 30, 2016. The cumulative incidence of perianal or rectovaginal fistulas was 18% after 10 years, 23% after 20 years, and 24% after 30-40 years from CD diagnosis. The cumulative incidence of perianal or rectovaginal fistulas was significantly lower in patients diagnosed in 1998 or after than in patients diagnosed before 1998 (P = 0.03, log-rank). Among 85 patients developing perianal or rectovaginal fistulas, 16 patients (18.8%) underwent proctectomy for the treatment of perianal or rectovaginal fistulas during follow-up.nnnCONCLUSIONSnIn a population-based inception cohort of CD, one-fifth of patients were diagnosed with at least 1 perianal or rectovaginal fistula. The cumulative probability of perianal or rectovaginal fistulizing disease has decreased over time.

Vedolizumab Drug Level Correlation With Clinical Remission, Biomarker Normalization, and Mucosal Healing in Inflammatory Bowel Disease

BACKGROUND/AIMSnThe clinical utility of vedolizumab (VDZ) trough levels (VTLs) in inflammatory bowel disease (IBD) is not well defined. The aims of this study are to determine the median VTLs and frequency of detected antibodies, the correlation of VTLs with C-reactive protein (CRP) and mucosal healing (MH), and the change in clinical management based on VTLs.nnnMETHODSnA cross-sectional study of IBD patients treated with VDZ with VTLs checked between July 1, 2016, and March 1, 2017, was conducted. Mucosal healing was defined as absence of mucosal ulcers in Crohns disease (CD) and Mayo endoscopic score ≤1 for ulcerative colitis (UC). Normal CRP was defined as ≤8 mg/L.nnnRESULTSnA total of 171 patients (62% CD, 31% UC, 7% indeterminate colitis) were included. Median VTLs was 15.3 ug/mL (range, 0-60), and 1 patient had detectable antibodies to VDZ. Patients with a normal CRP had a median VTLs of 17.3 ug/mL vs 10.7 ug/mL in high CRP patients (P = 0.046). This was noted in CD (20.3 vs 10.4 ug/mL; P = 0.005) but not in UC patients (14.4 vs 20.8; P = 0.72). Mucosal healing was achieved in 35% of patients (37 of 105); among these, median VTLs was 13.7 ug/mL vs 16.1 ug/mL in patients who did not achieve MH (P = 0.64). Vedolizumab trough levels resulted in a change in clinical management in 73%.nnnCONCLUSIONSnOur cohort showed a low rate of immunogenicity to VDZ and an association between VTLs and CRP in CD but not in UC patients. No relationship between VTLs and MH was detected. Vedolizumab trough level measurements altered management in approximately three fourths of patients.

Increased Risk of Acute Myocardial Infarction and Heart Failure in Patients With Inflammatory Bowel Diseases

Background & Aims There are conflicting data as to whether inflammatory bowel diseases (IBDs) increase risk for cardiovascular disease. We sought to examine the risk of acute myocardial infarction (AMI) and heart failure in patients with IBD. Methods We identified patients diagnosed with IBD in Olmsted County, Minnesota, from 1980 through 2010 (n = 736). For each patient, 2 individuals without IBD (controls, n = 1472) were randomly selected, matched for age, sex, and index date of disease diagnosis. Primary outcomes were AMI and heart failure. Cox proportional hazards analysis was used to estimate the risk of AMI and heart failure. Results After adjustments for traditional cardiovascular disease risk factors, IBD associated independently with increased risk of AMI (adjusted hazard ratio [aHR], 2.82; 95% CI, 1.98–4.04) and heart failure (aHR, 2.03; 95% CI, 1.36–3.03). The relative risk of AMI was significantly increased in patients with Crohn’s disease (aHR vs controls, 2.89; 95% CI, 1.65–5.13) or ulcerative colitis (aHR vs controls, 2.70; 1.69–4.35). The relative risk of AMI was increased among users of systemic corticosteroids (aHR vs controls, 5.08; 95% CI, 3.00–8.81) and nonusers (aHR vs controls, 1.79; 95% CI, 1.08–2.98). The relative risk of heart failure was significantly increased among patients with ulcerative colitis (aHR, 2.06; 95% CI, 1.18–3.65), but not Crohn’s disease. The relative risk of heart failure was increased among users of systemic corticosteroids (aHR, 2.51; 95% CI, 1.93–4.57), but not nonusers. Conclusions In a population‐based cohort study, we found that despite a lower prevalence of traditional risk factors for AMI and heart failure, patients with IBD are at increased risk for these cardiovascular disorders.

Retrospective Analysis of Safety of Vedolizumab in Patients With Inflammatory Bowel Diseases

BACKGROUND & AIMSnThere are few real-world data on the safety of vedolizumab for treatment of Crohns disease (CD) or ulcerative colitis (UC). We quantified rates and identified factors significantly associated with infectious and non-infectious adverse events in clinical practice.nnnMETHODSnWe performed a retrospective review of data from a multicenter consortium database (from May 2014 through June 2017). Infectious and non-infectious adverse events were defined as those requiring antibiotics, hospitalization, vedolizumab discontinuation, or resulting in death. Rates were quantified as proportions and events per 100 patient years of exposure (PYE) or follow up (PYF). We performed multivariable logistic regression analyses to identify factors significantly associated with events and reported as odds ratios (OR) with 95% CIs.nnnRESULTSnOur analysis comprised 1087 patients (650 with CD and 437 with UC; 55% female; median age, 37 years) with 861 PYE and 955 PYF. Infections were observed in 68 patients (6.3%; 7.9 per 100 PYE, 7.1 per 100 PYF); gastrointestinal infections (nxa0= 31, 2.4 per 100 PYE, 2.2 per 100 PYF) and respiratory infections (nxa0= 14, 1.6 per 100 PYE, 1.5 per 100 PYF) were the most common. Arthralgias were the most common non-infectious adverse events (nxa0= 31, 2.9%; 3.6 per 100 PYE). Two patients developed malignancies (squamous cell skin cancer and colorectal cancer; 0.23 per 100 PYE, 0.21 per 100 PYF). Active smoker status (OR, 3.39) and number of concomitant immunosuppressive agents (corticosteroids or immunomodulators; OR, 1.72 per agent) used were independently associated with infections.nnnCONCLUSIONnIn a retrospective cohort study of patients with IBD, we found vedolizumab to be well tolerated with an overall favorable safety profile. Active smoking and concomitant use of immunosuppressive agents were independently associated with infections.