Patient Resource Spotlight: Biosimilars: What You Should Know Webpage.

Professional Members of the Crohn's & Colitis Foundation are gastroenterologists, residents, fellows, advanced practice providers, nurses, and other healthcare professionals, just like you. They join to support research, to access professional and patient IBD education, and to establish themselves as IBD subject matter experts. Crohn's & Colitis Foundation Professional Members are the first to know about new patient resources, just like this one.

The Development and Initial Findings of A Study of a Prospective Adult Research Cohort with Inflammatory Bowel Disease (SPARC IBD).

BACKGROUND: Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. METHODS: We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. RESULTS: Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn's disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. CONCLUSION: The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.

Presence of Irritable Bowel Syndrome Symptoms in Quiescent Inflammatory Bowel Disease Is Associated with High Rate of Anxiety and Depression.

BACKGROUND: Inflammatory bowel disease (IBD; Crohn's disease, CD and Ulcerative colitis, UC) and irritable bowel syndrome (IBS) have overlapping symptoms. Few prevalence studies of IBS in quiescent IBD have used colonoscopy with histology to confirm inactive disease. The aims were (1) to determine the percentage of IBD patients in deep remission whose persistent IBS-like symptoms (IBD/IBS+) would cause them to be classified as having active disease, based on the calculation of Harvey Bradshaw Index (HBI) or UC disease activity index (UCDAI); (2) to identify demographic and disease characteristics that are associated with IBD/IBS+. METHODS: This was a prospective study at a single tertiary care IBD center. 96/112 patients with colonoscopy and histology confirmed quiescent disease consented and completed Rome III criteria for IBS Survey, and the hospital anxiety and depression scale (HADS). Other demographic and disease specific data were collected. RESULTS: 36% (28/77) and 37% (7/19) of CD and UC patients, respectively, met diagnostic criteria for IBS. Significantly higher HBI/UCDAI scores (p = 0.005) and low short inflammatory bowel disease questionnaire (SIBDQ) scores (p ≤ 0.0001) were seen in IBD/IBS+ patients. 29% of patients in deep remission were mis-categorized by HBI/UCDAI as having active disease when they fulfilled Rome III criteria for IBS. Psychiatric diagnosis (OR 3.53 95% CI 1.2-10.2) and earlier onset of IBD (OR 1.056 95% CI 1.015-1.096) were associated with IBD/IBS+. Patients fulfilling IBS criteria had higher hospital anxiety and depression scale (HADS). CONCLUSION: IBD/IBS+ affect scoring of IBD disease activity scales and become less useful in guiding treatment plans.

Advanced Age Does Not Negatively Impact Health-Related Quality of Life in Inflammatory Bowel Disease.

BACKGROUND: Health-related quality of life (HRQoL) is significantly impacted in patients with inflammatory bowel disease (IBD). Many studies have assessed HRQoL in patients of all ages, and few focus on the elderly. AIM: To determine the influence of advanced age (> 65 years) and age at diagnosis on patients with IBD. METHODS: This is a retrospective study of prospectively collected data from a single IBD tertiary referral center. Patients had disease activity indices [Harvey-Bradshaw index (HBI), Ulcerative Colitis Disease Activity Index (UCDAI), and Short Inflammatory Bowel Disease Questionnaire (SIBDQ)] recorded during every clinic visit. Three groups of patients: > 65 years, 41-64 years, and < 40 years with > 5 SIBDQ entries were included. Influence of disease type, disease duration, extent of involvement, and comorbidities such as cardiovascular (CV) disease, pulmonary disease, diabetes mellitus (DM), and psychological disorders were noted as confounders. Statistical analysis was performed using ANOVA, Pearson correlation, and logistic regression model. RESULTS: Disease severity indices significantly affected SIBDQ score in both Crohn's disease (CD) and ulcerative colitis (UC) (p < 0.001 for HBI in CD, p < 0.001 UCDAI in UC). Disease extent (p = 0.011) and psychological disorders (p < 0.001) significantly affected SIBDQ score in CD. Chronological age, age at diagnosis, disease duration, number of clinic visits, CV disease, pulmonary disease, and DM were not significant predictors of SIBDQ score (p > 0.05). CONCLUSIONS: HRQoL was negatively influenced by disease extent and psychological disorders in CD but not in UC patients. Advanced age was not a predictor of poor HRQoL in both CD and UC.

White Paper AGA: The Impact of Mental and Psychosocial Factors on the Care of Patients With Inflammatory Bowel Disease.

Patients with chronic medically complex disorders like inflammatory bowel diseases (BD) often have mental health and psychosocial comorbid conditions. There is growing recognition that factors other than disease pathophysiology impact patients' health and wellbeing. Provision of care that encompasses medical care plus psychosocial, environmental and behavioral interventions to improve health has been termed "whole person care" and may result in achieving highest health value. There now are multiple methods to survey patients and stratify their psychosocial, mental health and environmental risk. Such survey methods are applicable to all types of IBD programs including those at academic medical centers, independent health systems and those based within independent community practice. Once a practice determines that a patient has psychosocial needs, a variety of resources are available for referral or co-management as outlined in this paper. Included in this white paper are examples of psychosocial care that is integrated into IBD practices plus innovative methods that provide remote patient management.

Dyssynergic defecation: a treatable cause of persistent symptoms when inflammatory bowel disease is in remission.

BACKGROUND: Introduction of biologic agents in inflammatory bowel disease (IBD) has increased the likelihood of disease remission. Despite resolution of active inflammation, a subset of IBD patients report persistent defecatory symptoms. AIM: To evaluate a group of patients with inflammatory bowel disease with suspected functional defecatory disorders, by use of anorectal manometric testing and subsequent biofeedback therapy. METHODS: A group of IBD patients with persistent defecatory problems despite clinical improvement were included in this study. These patients had no evidence of left-sided disease. Endoscopic and radiographic study findings and timing in relation to the manometry study were recorded. Anorectal manometry was performed by the standard protocol and included rectal sensory assessment, ability to expel a balloon, and pressure dynamics with simulated defecation. RESULTS: Thirty IBD patients (Crohn's 23 patients; ulcerative colitis six patients) presented with defecatory disorders including constipation (67%) increased stooling (10%), and rectal urgency and/or incontinence and rectal pain (6%). All but one patient had anorectal manometric criteria of dyssynergia (presence of anismus motor pattern and inability to expel the balloon). Of the patients who completed biofeedback therapy, 30% had a clinically significant (≥7-point) improvement in SIBDQ score, with a reduction in health-care utilization after a six-month period (p=0.02). CONCLUSIONS: Despite remission, some inflammatory bowel disease patients have persistent defecatory symptoms. Defecatory symptoms may not be predictive of an underlying inflammatory disorder. Lack of inflammatory activity and absence of left-sided disease should prompt investigation of functional disorders. Anorectal manometric testing and biofeedback therapy for patients with a diagnosis of dyssynergia may be a useful therapy.

Surgical outcomes in the elderly with inflammatory bowel disease are similar to those in the younger population.

BACKGROUND: Inflammatory bowel disease (IBD) has a bimodal distribution with approximately 15 % of patients manifesting after age 65. Previous reports suggest an increased risk of surgical complications in the elderly. AIM: To compare surgical outcomes in elderly IBD patients (≥ 65 years at the time of surgery) to matched younger IBD cohorts. METHODS: This was a retrospective cohort study at a single academic center of patients who underwent surgery for IBD. Forty-two elderly patients (≥ 65 years) were matched at least 1:1 (median 1:5) to patients in each of three control groups [18-35 years (n = 71); 36-49 years (n = 62); 50-64 years (n = 58)] according to gender, disease type/location, and type of surgery. Postoperative complications were compared. Patient characteristics were used in multivariate risk models. Analysis was performed using ordinary logistic regression. RESULTS: Twenty ileal or ileocolonic resections, 12 partial or total colectomies, four stricturoplasties, and six laparoscopic partial or total colectomies were performed in the elderly group. The post-operative complication rate was not statistically different between the elderly and younger cohorts (38 % vs. 39 % vs. 40 % vs. 48 % in the 18-35, 36-49, 50-64, and ≥ 65 years groups, respectively, p = 0.26). The only significant risk factors for complication were Charlson comorbidity index (p = 0.0002), preoperative hemoglobin (p = 0.0065), total parenteral nutrition use (p = 0.024), and failed medical therapy (as the indication for surgery) (p = <0.0001). CONCLUSIONS: The surgical complication rate among elderly and younger IBD patients was similar. Advanced age by itself should not be considered a risk factor for adverse operative outcome.

Impact of pregnancy on health-related quality of life of patients with inflammatory bowel disease.

OBJECTIVE: To examine the impact of pregnancy on health-related quality of life (HRQoL) of women with inflammatory bowel disease (IBD). METHODS: This was a retrospective study in a tertiary referral center and included women with ≥2 short inflammatory bowel disease questionnaire (SIBDQ) scores obtained during their pregnancy. Regression models were used to identify independent factors influencing SIBDQ scores and changes of SIBDQ scores at different time points. RESULTS: A total of 32 women (23 CD, 9 UC) with a mean age at pregnancy of 29.4 years and a mean disease duration of 7.8 years were included in the study. The mean pre-pregnancy SIBDQ score in our cohort was 49, which was significantly lower than the values during (55, P < 0.001) and post-pregnancy (53, P = 0.01). The score during pregnancy directly correlated with the pre-pregnancy SIBDQ score (correlation co-efficient 0.50, P = 0.003). Half of the patients had a ≥7-point increase in SIBDQ scores during pregnancy. Change in SIBDQ scores during pregnancy was inversely related to the pre-pregnancy score (-0.47, 95% CI -0.75 to -0.20) and changes in disease activity during pregnancy (-1.80, 95% CI -0.75 to -0.20). CONCLUSIONS: Half of the pregnant women with IBD in our cohort experienced improvement in their HRQoL. Pre-pregnancy HRQoL is predictive of HRQoL during pregnancy, supporting the need for optimizing disease activity prior to conception.

QuantiFERON TB gold testing for tuberculosis screening in an inflammatory bowel disease cohort in the United States.

BACKGROUND: Reactivation of latent Mycobacterium tuberculosis (TB) is a rare, yet devastating infectious complication associated with anti-tumor necrosis factor alpha (TNF-α) therapy. We evaluated the performance of the QuantiFERON TB Gold test (QFT-G) for TB screening in a cohort of inflammatory bowel disease (IBD) patients in the United States. METHODS: We performed a retrospective, observational study of patients initiated and/or maintained on an anti-TNF-α agent in a single IBD referral center and recorded the frequency and the test results of QFT-G testing and the rate of TB reactivation. RESULTS: 512 QFT-G tests were done in 340 patients. Five patients (1.5%) had a positive, nine (2.7%) indeterminate, and 326 patients (95.8%) had a negative QFT-G. After a mean follow-up of 17 months there was one case of TB reactivation (0.3%). The use of immunosuppressive therapy or anti-TNF therapy at the time of testing did not affect the results of the QFT-G testing. Test-retest had substantial concordance (κ = 0.72). 25% of patients (n = 85) had TST testing. Concordance between the TST and QFT-G was found to be moderate (κ = 0.4152, P = 0.0041). CONCLUSIONS: Most patients with negative QFT-G tolerated anti-TNF therapy with no evidence of TB reactivation. Concomitant use of immunosuppressive therapy or anti-TNF did not seem to affect QFT-G results. One patient had an indeterminate QFT-G while on infliximab and later developed miliary TB. Concordance with TST is moderate.

Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?

BACKGROUND: Impairment of health-related quality of life (HRQoL) is an important concern in inflammatory bowel disease (IBD; ulcerative colitis [UC], Crohn's disease [CD]). Between 2%-10% of patients with IBD have primary sclerosing cholangitis (PSC). There has been limited examination of the disease-specific HRQoL in this population compared to non-PSC IBD controls. METHODS: This was a retrospective, case-control study performed at a tertiary referral center. Cases comprised 26 patients with a known diagnosis of PSC and IBD (17 UC, 9 CD). Three random controls were selected for each case after matching for IBD type, gender, age, and duration of disease. Disease-specific HRQoL was measured using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ). Disease activity for CD was measured using the Harvey-Bradshaw index (HB) and using the UC activity index for UC. Independent predictors of HRQoL were identified. RESULTS: There was no significant difference in the age, gender distribution, or disease duration between PSC-IBD and controls. There was no difference in use of immunomodulators or biologics between the 2 groups. Mean SIBDQ score was comparable between PSC-IBD patients (54.5) and controls (54.1), both for UC and CD. Likewise, the disease activity scores were also similar (2.8 versus 3.1, P = 0.35). On multivariate analysis, higher disease activity score (-1.33, 95% confidence interval [CI] 95% CI -1.85 to -0.82) and shorter disease duration were predictive of lower HRQoL. Coexisting PSC did not influence IBD-related HRQoL. There was a higher proportion of permanent work disability in PSC-IBD (7.7%) compared to controls (0%). CONCLUSIONS: PSC does not seem to influence disease-specific HRQoL in our patients with IBD but is associated with a higher rate of work disability.

Upper esophageal sphincter and gastroesophageal junction pressure changes act to prevent gastroesophageal and esophagopharyngeal reflux during apneic episodes in patients with obstructive sleep apnea.

BACKGROUND: Gastroesophageal reflux (GER) is thought to be induced by decreasing intraesophageal pressure during obstructive sleep apnea (OSA). However, pressure changes in the upper esophageal sphincter (UES) and gastroesophageal junction (GEJ) pressure during OSA events have not been measured. The aim of this study was to determine UES and GEJ pressure change during OSA and characterize the GER and esophagopharyngeal reflux (EPR) events during sleep. METHODS: We studied 15 controls, nine patients with GER disease (GERD) and without OSA, six patients with OSA and without GERD, and 11 patients with both OSA and GERD for 6 to 8 h postprandially during sleep. We concurrently recorded the following: (1) UES, GEJ, esophageal body (ESO), and gastric pressures by high-resolution manometry; (2) pharyngeal and esophageal reflux events by impedance and pH recordings; and (3) sleep stages and respiratory events using polysomnography. End-inspiration UES, GEJ, ESO, and gastric pressures over intervals of OSA were averaged in patients with OSA and compared with average values for randomly selected 10-s intervals during sleep in controls and patients with GERD. RESULTS: ESO pressures decreased during OSA events. However, end-inspiratory UES and GEJ pressures progressively increased during OSA, and at the end of OSA events were significantly higher than at the beginning (P < .01). The prevalence of GER and EPR events during sleep in patients with OSA and GERD did not differ from those in controls, patients with GERD and without OSA, and patients with OSA and without GERD. CONCLUSIONS: Despite a decrease in ESO pressure during OSA events, compensatory changes in UES and GEJ pressures prevent reflux.

Terminating motor events for TLESR are influenced by the presence and distribution of refluxate.

Transient lower esophageal sphincter relaxation (TLESR) is frequently associated with reflux events and terminates with a primary or secondary peristaltic wave. However, it is unclear whether the presence and properties of the refluxate affect TLESR-termination events. The aims of this study were to determine the pattern of terminating esophageal motor activity after TLESR in healthy subjects and factors affecting the type of terminating motor event. Fifteen healthy subjects (7 men, age 18-56) were studied. High-resolution manometry and impedance/pH monitoring were performed simultaneously in supine position for 2 h after subjects took a 1,000-kcal meal (Awake Study). This procedure was repeated during the night under polysomnographic recording for 6-8 h after consuming a 1,000-kcal meal (Sleep Study). We categorized three types of TLESR-terminating motor events, primary peristalsis (PP), full secondary contraction (FSC), which propagated the entire esophagus, and partial secondary contractions (PSC), which started distal to the upper esophageal sphincter. Overall, 289 TLESR events were found. The percentages of TLESR events terminated by PP, FSC, and PSC were 22%, 14%, and 64%, respectively. TLESR events terminated by PP were less likely to be accompanied by reflux events. TLESR events terminated by FSC were significantly more likely to have evidence for proximal esophageal reflux and esophago-pharyngeal reflux. Findings were similar in awake and sleep states. We concluded that, in healthy recumbent subjects, the most common TLESR-termination event is a secondary contraction, rather than PP. Presence and distribution of the refluxate is a major influence on the type of terminating contraction.

Manometric evidence for a phonation-induced UES contractile reflex.

The mechanism against entry of gastric content into the pharynx during high-intensity vocalization such as seen among professional singers is not known. We hypothesized that phonation-induced upper esophageal sphincter (UES) contraction enhances the pressure barrier against entry of gastroesophageal contents into pharynx. To determine and compare the effect of phonation on luminal pressures of the esophagus and its sphincters, we studied 17 healthy volunteers (7 male, 10 female) by concurrent high-resolution manometry and voice analysis. We tested high- and low-pitch vowel sounds. Findings were verified in six subjects by UES manometry using a water-perfused sleeve device. Eight of the volunteers (2 male, 6 female) had concurrent video fluoroscopy with high-resolution manometry and voice recording. Fluoroscopic images were analyzed for laryngeal movement. To define the sex-based effect, subgroup analysis was performed. All tested phonation frequencies and intensities induced a significant increase in UES pressure (UESP) compared with prephonation pressure. The magnitude of the UESP increase was significantly higher than that of the distal esophagus, the lower esophageal sphincter (LES), and the stomach. Concurrent videofluoroscopy did not show posterior laryngeal movement during phonation, eliminating a purely mechanical cause for phonation-induced UESP increase. Subgroup analysis demonstrated phonation-induced UESP increases in males that were significantly greater than those of females. Phonation induces a significant increase in UESP, suggesting the existence of a phonation-induced UES contractile reflex. UESP increase due to this reflex is significantly higher than that of the distal esophagus, LES, and stomach. The phonation-induced UESP increase is influenced by sex.

Expression of nonclassical class I molecules by intestinal epithelial cells.

It is well recognized that the nature of the immune response is different in the intestinal tract than in peripheral lymphoid organs. The immunologic tone of the gut-associated lymphoid tissue is one of suppression rather than active immunity, distinguishing pathogens from normal flora. Failure to control mucosal immune responses may lead to inflammatory diseases such as Crohn's disease (CD) and ulcerative colitis (UC) and celiac disease. It has been suggested that this normally immunosuppressed state may relate to unique antigen-presenting cells and unique T-cell populations. The intestinal epithelial cell (IEC) has been proposed to act as a nonprofessional antigen-presenting cell (APC). Previous studies have suggested that antigens presented by IECs result in the activation a CD8(+) regulatory T-cell subset in a nonclassical MHC I molecule restricted manner. We therefore analyzed the expression of nonclassical MHC I molecules by normal IECs and compared this to those expressed by inflammatory bowel disease (IBD) IECs. Normal surface IEC from the colon and, to a much lesser extent, the small bowel express nonclassical MHC I molecules on their surface. In contrast, mRNA is expressed in all intestinal epithelial cells. Surface IEC express CD1d, MICA/B, and HLA-E protein. In contrast, crypt IECs express less or no nonclassical MHC I molecules but do express mRNA for these molecules. Furthermore, the regulation of expression of distinct nonclassical class I molecules is different depending on the molecule analyzed. Interestingly, IECs derived from patients with UC fail to express any nonclassical MHC I molecules (protein and HLA-E mRNA). IECs from CD patients express HLA-E and MICA/B comparable to that seen in normal controls but fail to express CD1d. Thus, in UC there may be a failure to activate any nonclassical MHC I molecule restricted regulatory T cells that may result in unopposed active inflammatory responses. In CD only the CD1d-regulated T cells would be affected.

Adequacy of colonoscopic biopsy specimens for molecular analysis: a comparative study with colectomy tissue.

Molecular analyses of tumors are increasingly useful for prognosis and for guiding therapy. Colonoscopic biopsy provides the first source of tissue for most cases of colorectal carcinoma and therefore might become an important source for molecular analyses. We have addressed the question whether molecular analyses of colonoscopic biopsy yield results similar to the findings from the surgical specimen. Further, we analyzed 2 separate areas of the colectomy specimen to assess tumor heterogeneity. We evaluated 3 samples from each of 67 patients for point mutations in the KRAS gene, loss of heterozygosity (LOH) at the Adenomatous Polyposis Coli (APC) and Deleted in Colon Cancer (DCC) genes and for microsatellite instability (MSI) using polymerase chain reaction based techniques. The average time interval between biopsy and surgery was 2.2+/-0.15 weeks. Lesions were from all colon segments and all surgical stages. The degree of agreement between the biopsy and surgical sites was high for APC LOH, MSI, and KRAS mutations (kappa=0.85, 1.00, and 0.93, respectively) but less so for DCC LOH (kappa=0.62). Colonoscopic biopsies are an acceptable source of neoplastic DNA for studies of KRAS, APC LOH, and MSI, but less so for DCC LOH, primarily resulting from technical considerations.