Immunosuppression for management of Crohn's disease

We read with interest the study by Reena Khanna and colleagues describing early combined immunosuppression (ECI) for the management of Crohn's disease (REACT trial). The authors aimed to compare the effectiveness of ECI treatment (an anti-TNF drug with antimetabolite treatment) with a conventional step-up approach in a real-life setting

Photosensitivity to Ultraviolet Light in Patients with Inflammatory Bowel Disease Newly Initiating Immunosuppressive Therapy

To the Editor: We read with interest the article by Kopylov et al, particularly with respect to the increased risk of nonmelanoma skin cancer (NMSC) seen in patients with inflammatory bowel disease (IBD) on thiopurines. Previous studies have also shown that patients with IBD with previous and ongoing exposure to thiopurines are at increased risk. Importantly, unlike lymphoma risk,4 the risk of NMSC persists even after discontinuation of thiopurines, suggesting a mechanism of nonreversible DNA damage

Patients With Pouchitis Demonstrate a Significant Cost Burden in the First Two Years After Ileal Pouch-Anal Anastomosis

Pouchitis, the most common long-term complication after colectomy with IPAA for UC, can lead to increased health-care costs and diminished quality of life. In this study, we aimed to compare the total costs among patients diagnosed with pouchitis in the first 2 years after an IPAA to those among patients who were not diagnosed with pouchitis, using a large administrative claims database. Additionally, we aimed to investigate the specific drivers of cost among patients with an IPAA during the two-year study period, including inpatient hospitalizations, Emergency Department (ED) visits, and pharmacy-related costs

Incidence, Risk Factors, and Outcomes of Pouchitis and Pouch-Related Complications in Patients With Ulcerative Colitis

Background & Aims: Acute pouchitis is the most common non-surgical complication after restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We used validated case-finding definitions for pouchitis to search administrative claims data and determine the incidence of pouchitis in the first 2 years after IPAA. Methods: We identified all patients who underwent proctocolectomy with IPAA for UC in the IQVIA Legacy PharMetrics Adjudicated Claims Database, from January 1, 2007 through June 1, 2016. The primary outcome was the development of pouchitis within 2 years after IPAA. Secondary outcomes included isolated acute vs recurrent pouchitis, immunosuppressive therapy, further surgery, and admission to the hospital. Results: Among 594 patients, the cumulative incidence of pouchitis within 2 years of IPAA was 48% (95% CI, 44%–52%). The cumulative incidence of isolated acute pouchitis was 29% (95% CI, 26%–33%). Compared to patients with isolated acute pouchitis, patients who received a diagnosis of recurrent pouchitis (cumulative incidence, 19%: 95% CI, 16%–22%) demonstrated increased outpatient visits, emergency department visits, and inpatient admissions (all P < .001). Patients who developed pouchitis were more likely to have a history of primary sclerosing cholangitis (adjusted odds ratio [aOR], 3.94; 95% CI, 1.05–14.8) and anti-tumor necrosis factor alpha therapy prior to colectomy (aOR 1.63; 95% CI, 1.09–2.45). Among patients with pouchitis, the cumulative frequency of new immunosuppressive therapy was 40% (95% CI, 35%–46%) and the cumulative incidence of pouch excision was 1.0% (95% CI, 0.4%–3.0%). The cumulative incidence of a new diagnosis of Crohn's disease after IPAA for UC was 9.0% (95% CI, 7.2%–11%). Conclusions: In a geographically diverse population, 48% of patients with UC developed pouchitis within the first 2 years after IPAA. Patients with pouchitis had greater use of healthcare resources, indicating a significant burden of disease

Decreasing Colectomy Rate for Ulcerative Colitis in the United States Between 2007 and 2016: A Time Trend Analysis

BACKGROUND: Improved treatment approaches for ulcerative colitis (UC), including novel medications, might reduce the need for colectomy. We performed a retrospective cohort study of adult patients (age 18-64) with UC in the United States to examine time trends for colectomy and biologic use from 2007 to 2016. METHODS: We estimated quarterly rates for colectomy and biologic use using the IQVIA Legacy PharMetrics Adjudicated Claims Database. We used interrupted time series methods with segmented regression to assess time trends with 95% confidence intervals (CIs) for biologic use and colectomy before and after the emergence of newly available biologic therapies in 2014. RESULTS: Among 93,930 patients with UC, 2275 (2.4%) underwent colectomy from 2007 to 2016. Biologic use rates increased significantly from 2007 to 2016, from 131 per 1000 person-years in 2007 (95% CI, 121 to 140) to 589 per 1000 person-years in 2016 (95% CI, 575 to 604; P < 0.001). Colectomy rates decreased significantly between 2007 and 2016, from 7.8 per 1000 person-years (95% CI, 7.4 to 8.2) to 4.2 per 1000 person-years in 2016 (95% CI, 3.2 to 5.1; P < 0.001). An interruption in 2014 was associated with a positive trend deflection for biologic use (+72 treatments per 1000 person-years per year (95% CI, 61 to 83) and a negative trend deflection for colectomy (-0.76 per 1000 person-years per year; 95% CI, -1.47 to -0.05). CONCLUSIONS: Among commercially insured patients in the United States from 2007 to 2016, biologic use rates increased, colectomy rates decreased, and both trends were impacted by the interruption in 2014. These findings suggest that new biologic therapies may have contributed to decreased colectomy rates

Asians Have More Perianal Crohn Disease and Ocular Manifestations Compared with White Americans

Background: Inflammatory bowel disease (IBD) is increasing in Asians. We sought to better understand differences in IBD between Asians and whites in the United States (US). Methods: We used data from the Sinai-Helmsley Alliance for Research Excellence cohort to assess disease characteristics for US-born Asians, Asian immigrants, and whites. We used bivariate analyses to describe clinical characteristics by race. We used logistic regression to determine baseline odds of immunosuppression and binomial regression to estimate risk ratios for worsening disease at follow-up. Results: We included 5,223 whites, 35 US-born Asians, and 81 Asian immigrants. Crohn disease (CD) was present in 64% of whites, 40% of US-born Asians, and 51% of Asian immigrants. At baseline, 58% of whites, 62% of US-born Asians, and 67% of Asian immigrants were in remission by disease activity index score (p = 0.238). There were no significant differences in CD location and behavior or ulcerative colitis extent. Asians had significantly more perianal disease than whites (33 vs. 18%, p = 0.007). Asians were more likely to have ocular manifestations than whites (3.4 vs. 0.7%, p = 0.022). Asians were also significantly less likely to be depressed than whites (25 vs. 35%, p = 0.022). Adjusting for confounders, Asians had half the odds of being treated with biologics compared with whites (OR: 0.45, 95% CI: 0.30-0.67). Adjusting for disease behavior and remission status, there were no differences in IBD-related surgery or hospitalization, new biologic or steroid prescription, or relapse rates between Asians and whites at follow-up. Conclusion: Asians are more likely to have perianal disease and ocular extraintestinal manifestations. After controlling for confounders, Asians were less likely to be treated with biologic agents. Despite this, there were no significant differences in outcomes over time between Asians and whites. Differences in disease phenotypes in Asians may reflect differences in genetics

The Cumulative Incidence of Pouchitis in Pediatric Patients With Ulcerative Colitis

Background: Despite highly effective therapies, many children develop medically refractory ulcerative colitis (UC) and undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). We sought to determine the incidence, risk, and burden of pouchitis in the first 2 years following the final stage of IPAA in pediatric UC patients. Methods: Within the IQVIA Legacy PharMetrics Adjudicated Claims Database, we identified pediatric patients with UC who underwent proctocolectomy with IPAA between January 1, 2007, and June 30, 2015. We utilized International Classification of Diseases-Ninth Revision-Clinical Modification or International Classification of Diseases-Tenth Revision-Clinical Modification codes to identify patients with UC and Current Procedural Terminology codes to identify colectomy and IPAA. Continuous variables were compared using t tests and Wilcoxon rank sum testing, while categorical variables were compared using chi-square testing. Results: A total of 68 patients with an IPAA were identified. In the first 2 years following IPAA, the cumulative incidence of pouchitis was 54%. Patients with pouchitis required more outpatient visits in the first 2 years after IPAA (mean 21.8 vs 10.2; P =. 006) and were more likely to be hospitalized compared with patients without pouchitis (46% vs 23%; P =. 045). Patients with pouchitis also demonstrated higher mean total costs in year 1 and year 2 ($27 489 vs$8032 [P =. 001] and $27 699 vs$6058 [P =. 003], respectively). Conclusions: Our findings confirm the high incidence of pouchitis demonstrated in earlier single-center studies of pediatric patients undergoing proctocolectomy with IPAA for UC. Identification of risk factors for pouchitis would be useful to optimize early intervention

Transmural Inflammation, Ileitis, and Granulomas at the Time of Proctocolectomy in Patients with Ulcerative Colitis Do Not Predict Future Development of Pouchitis

Background: The most common complication following ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is pouchitis. Our study aimed to investigate the relationship between histopathologic findings of ileitis, granuloma, or transmural inflammation on the colectomy specimen of patients with clinically and endoscopically diagnosed UC and the development of pouchitis within the first 2 years after IPAA. Methods: We performed a retrospective cohort study evaluating patients undergoing colectomy with IPAA for UC between January 1, 2004 and December 31, 2016. Bivariate analyses were conducted to evaluate the relationship between clinical factors and the development of pouchitis. We performed multivariate logistic regression to evaluate the relationship between histologic, clinical, and demographic factors at the time of colectomy and subsequent development of pouchitis. Results: Among 626 patients, pouchitis occurred in 246 (39%). Patients with primary sclerosing cholangitis were more likely to develop pouchitis (adjusted odds ratio [aOR] 2.81, 95% confidence interval [CI] 1.02-7.72), as were patients with a family history of inflammatory bowel disease (aOR 1.75, 95% CI 1.11-2.77). Histologic findings of ileitis, granuloma, or transmural inflammation were not associated with an increased odds of developing pouchitis (aOR 0.70, 95% CI 0.45-1.08). Discussion/Conclusion: Patients with ileitis, granulomas, or transmural inflammation at the time of colectomy were not at greater risk for development of pouchitis in the 2 years after IPAA. These pathological findings should not preclude IPAA for UC

Pouch-Related Symptoms and Quality of Life in Patients with Ileal Pouch-Anal Anastomosis

Background: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the standard surgical treatment for the majority of patients with inflammatory bowel disease (IBD) who require colectomy. We evaluated the prevalence of pouch-related symptoms among the Crohn's and Colitis Foundation of America Partners cohort and the effect of pouch-related symptoms on Patient-Reported Outcome Measurement Information System measures. Methods: We performed analyses nested in the Crohn's and Colitis Foundation of America Partners cohort. We used bivariate analyses to compare demographics and medication use among patients with ulcerative colitis or indeterminate colitis and pouch-related symptoms and those with IPAA without symptoms. We also compared Patient-Reported Outcome Measurement Information System domains (measured in T-scores) and short IBD questionnaire quality of life scales between symptomatic pouch patients (over the past 6 mo) and those without symptoms. Results: Among 243 patients reporting a history of IPAA, 199 (82%) reported a history of pouch symptoms. Patients with recent pouch symptoms demonstrated higher mean T-scores in pain interference (53.0 versus 45.3; P < 0.001), depression (51.0 versus 46.4; P = 0.002), and fatigue (56.3 versus 47.0; P < 0.001). Symptomatic pouch patients reported lower mean scores in social role satisfaction (47.4 versus 54.6) and short IBD questionnaire (4.8 versus 5.8) (both P < 0.001). These differences were all clinically meaningful. Conclusions: In a large sample of patients with IBD, nearly all patients with IPAA reported a history of pouch symptoms. Patients experiencing symptoms within the 6 months before the survey assessment demonstrated clinically meaningful decrements in patient-reported outcomes in multiple domains of physical and psychosocial functioning

Creation of a Case-Finding Definition for Identifying Patients With Acute Pouchitis in Administrative Claims Data

Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4–6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis