Search

Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population. Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD. This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes. 212 cases were identified—108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p

Background Prior research demonstrates Crohn’s disease patients often do well in pregnancy; however, less is known about the risk of flare in the postpartum period. Methods A retrospective chart review was conducted at a tertiary care inflammatory bowel disease center. All pregnant women with Crohn’s disease who were followed in the postpartum period, defined as 6 months after delivery, were included. Statistical analysis included χ 2 analysis, Wilcoxon rank sum test, and logistic regression analysis. The primary outcome of interest was rate of flare in the postpartum period. Results There were 105 patients included in the study, with a majority (68%) on biologic medication during pregnancy. Thirty-one patients (30%) had a postpartum flare at a median of 9 weeks (range 2–24 weeks). Twenty-five patients (81%) had their postpartum flare managed in the outpatient setting with medications (only 4 of these patients required prednisone). 6 of 31 patients (19%) were hospitalized at a median of 4 weeks (range 2–26 weeks) after delivery, requiring intravenous corticosteroids or surgery. In multivariable regression, there was no significant increase in risk of postpartum flare with increasing maternal age, flare during pregnancy, or steroid or biologic use during pregnancy. Smoking during pregnancy increased risk of postpartum flare (odds ratio, 16.2 [1.72–152.94], P Conclusion In a cohort of Crohn’s disease patients, 30% experienced a postpartum flare despite being on medical therapy, but most were able to be managed in the outpatient setting.

Background This study evaluated synchronous audiovisual telehealth and audio-only visits for patients with inflammatory bowel disease (IBD) to determine frequency of successful telehealth visits and determine what factors increase the likelihood of completion. Methods Data were collected from March to July 2020 in a tertiary care adult IBD clinic that was transitioned to a fully telehealth model. A protocol for telehealth was implemented. A retrospective analysis was performed using electronic medical record (EMR) data. All patients were scheduled for video telehealth. If this failed, providers attempted to conduct the visit as audio only. Results Between March and July 2020, 2571 telehealth visits were scheduled for adult patients with IBD. Of these, 2498 (99%) were successfully completed by video or phone. Sixty percent were female, and the median age was 41 years. Eighty six percent of the population was white, 8% black, 2% other, and 4% were missing. Seventy-five percent had commercial insurance, 15% had Medicare, 5% had Medicaid, and 5% had other insurance. No significant factors were found for an attempted but completely failed visit. Using a multivariate logistic regression model, increasing age (odds ratio, 1.80; 95% CI, 1.55–2.08; P Conclusions There is a high success rate for telehealth within an IBD population with defined clinic protocols. Certain patient characteristics such as age, race, and health insurance type increase the risk of failure of a video visit.

Background A Functional Medicine program was developed at an inflammatory bowel disease (IBD) center with the goal of integrating strategies to address modifiable lifestyle factors and to complete a 6-week elimination diet under the direction of a trained Functional Medicine dietitian and Functional Medicine providers. Methods From January 2019 to November 2019, patients with controlled, but persistent, symptoms from IBD were offered enrollment. Each of the 5 visits incorporated an educational session focused on nutrition followed by a session focusing on modifiable lifestyle factors. The patients were placed on a supervised 6-week elimination diet. At each visit, patients completed the SIBDQ (Short Inflammatory Bowel Disease Questionnaire), FSS (Fatigue Severity Scale), PSQI (The Pittsburgh Sleep Quality Index), and MSQ (Medical Symptoms Questionnaire). Statistical analysis was performed using the Wilcoxon matched pairs signed-rank test. Results Nineteen patients enrolled (2 men: 1 ulcerative colitis [UC], 1 Crohn’s disease [CD]; 17 women: 3 UC, 14 CD). 15 patients completed all modules. There was improvement in all patient-reported outcomes (PROs) (FSS, P < .001; PSQI, P < .001; SIBDQ, P < .001; MSQ, P < .001). Every patient who completed the last session demonstrated weight loss. Conclusions The psychoemotional roots to immune disease states, particularly IBD, are complicated and often not addressed in traditional care. We are just beginning to understand the impact of nutrition, sleep, stress, movement, and relationships on IBD. In this cohort, utilizing Functional Medicine as an adjunct to traditional care resulted in improvement in all PROs.

While the pathogenesis of inflammatory bowel disease (IBD) is incompletely understood, disruption of epithelial integrity is suspected to play a prominent role in disease initiation and progression. Currently, there is no convenient way to measure this in vivo. Our aim is to determine whether a mucosal integrity (MI) testing device that has been used to measure MI in the esophagus can also be used to measure barrier function in the colon during colonoscopy. Mucosal integrity testing was measured in patients with IBD (n = 17) and controls (n = 7) during colonoscopy. During the procedure, an MI catheter was passed down the working channel of the colonoscope and placed along the mucosal wall to measure MI in the rectum, left, transverse, and right colon. In patients with IBD, MI measurements and biopsies were taken in areas which appeared inflamed when present. We then determined if there was a significant difference in MI between patients with IBD and controls. MI was significantly higher in the rectum of patients with IBD (CD and UC combined) versus control colons [767 (618–991) vs. 531 (418–604) ohms, P

Background Tofacitinib has been approved for moderate-to-severe ulcerative colitis and studied in Crohn’s disease. Understanding medication adherence to oral medications in severe disease is essential. Methods We retrospectively reviewed adherence and real-world outcomes of inflammatory bowel disease patients who initiated tofacitinib at a single care center. Adherence was measured by proportion of days covered. Results Sixty-three patients were identified. All patients failed at least one prior biologic therapy. Mean proportion of days covered was 95.7% for ulcerative colitis and 93.1% for Crohn’s disease. Significant clinical and endoscopic response was seen. Conclusion Adherence was high in a cohort with highly refractory disease.

Background In inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), nonadherence to biologic therapy increases risk of disease flare. The aim of this study was to identify risk factors for nonadherence. Methods This was a single-center retrospective study evaluating patients with IBD treated at a tertiary care center and prescribed self-injectable biologic therapy using the center’s specialty pharmacy. Adherence was defined using medication possession ratio (MPR). Nonadherence was defined as MPR Results Four hundred sixty patients (n = 393 with CD and n = 67 with UC) were evaluated with mean MPR (interquartile range) equaling 0.89 (0.48–1). Overall, 69% of patients were adherent (defined as MPR ≥0.86), 66% of patients with CD and 87% of patients with UC. In univariate analysis, several factors increased risk of nonadherence: CD diagnosis, insurance type, psychiatric history, smoking, prior biologic use, and narcotic use (P < 0.05). In multivariable analysis, Medicaid insurance (odds ratio [OR], 5.5; 95% confidence interval [CI], 1.85–15.6) and CD diagnosis (OR, 2.8; 95% CI, 1.3–6.0) increased risk of nonadherence. In CD, as the number of risk factors increased (narcotic use, psychiatric history, prior biologic use, and smoking), the probability of nonadherence increased. Adherence was 72% in patients with 0–1 risk factors, decreasing to 62%, 61%, and 42% in patients with 2, 3, and 4 risk factors, respectively (P < 0.05). Conclusions This study identified risk factors for nonadherence to biologic therapy. In patients with CD, the probability of nonadherence increased as the number of risk factors increased.

Background and Objectives The safety of inflammatory bowel disease medications during lactation is of significant relevance to women of childbearing potential. Available data regarding the transfer of biologic agents for inflammatory bowel disease via breast milk are limited to case reports. The objective of this prospective postmarketing lactation study was to assess vedolizumab concentrations in breast milk from lactating vedolizumab-treated women with inflammatory bowel disease. Methods Breast milk was serially collected throughout the dosing interval from 11 patients receiving established intravenous vedolizumab 300-mg maintenance therapy every 8, 6, or 4 weeks. Maternal safety was also assessed. Results Vedolizumab was detectable in ~90% of milk samples collected from all patients. Following the day 1 dose, vedolizumab milk concentrations increased with a median of 3–4 days to peak concentration, and subsequently decreased exponentially. For the nine patients receiving vedolizumab every 8 weeks, the average relative infant dose was 20.9%. Using a mean trough serum concentration of 11.2 µg/mL from historical studies, the ratio of mean vedolizumab milk-to-serum concentration was ~ 0.4 to 2.2%, consistent with published data on vedolizumab and other monoclonal antibody therapeutics for inflammatory bowel disease. The maternal safety profile was similar to that observed in previous vedolizumab studies. Published vedolizumab studies also showed no adverse findings for infants breastfed by vedolizumab-treated mothers. Conclusions Vedolizumab was present in human breast milk at a low level. The decision to use vedolizumab should balance the benefit of therapy to the mother and the potential risks to the infant. Trial Registration ClinicalTrials.gov, NCT02559713; registered 24 September, 2015.

Background The effectiveness and safety of gastroenterologist (GI)-lead treatment of iron deficiency anemia (IDA) in inflammatory bowel disease (IBD) have not been well-studied. Methods A retrospective chart review of patients with IBD, IDA, and evidence of treatment with iron at a tertiary IBD center was conducted. Results In 351 patients, hemoglobin and quality of life scores increased significantly after treatment with iron. Twelve of 341 patients treated with intravenous iron had an adverse effect. Twenty-seven patients required a hematology referral. Conclusion GIs should consider treating patients with IBD and IDA with intravenous iron as it is safe and effective., Lay Summary We reviewed records of patients with anemia and inflammatory bowel disease and found that gastroenterologists can effectively and safely treat anemia in these patients. This improved patients’ quality of life. Most patients did not need to see a separate specialist.

Vedolizumab is a monoclonal antibody used to treat inflammatory bowel disease (IBD). There is little known about the safety and comparative efficacy of this agent in the elderly population.Here, we present data on the safety and comparative efficacy of vedolizumab versus tumor necrosis factor α antagonists (anti-TNF) in elderly patients with IBD.This retrospective cohort study included IBD patients started on vedolizumab or anti-TNF at age 60 or older at a single tertiary IBD center. Safety was evaluated by assessing for the development of serious infection. The comparative needs for IBD-related surgery, IBD-related hospitalization, and drug discontinuation for any reason were obtained. Efficacy was assessed by comparing changes in endoscopic, histologic, and patient-report outcomes.212 cases were identified-108 patients treated with vedolizumab and 104 patients treated with anti-TNF. There were no significant differences between cohorts in serious infection, surgical intervention, or IBD-hospitalization-free survival (p = NS). Drug discontinuation survival was different between anti-TNF and vedolizumab (p = 0.02) with more patients remaining on vedolizumab at the time of last follow-up (51.9% vs. 25.9%). Endoscopic remission and response rates were higher in the vedolizumab versus anti-TNF group (65.7% vs. 45.2%, p = 0.02; 80.0% vs. 59.3%, p 0.001).In a cohort of IBD patients over age 60, vedolizumab showed no statistically significant differences in infection, hospitalization, or surgical intervention-free survival as compared to anti-TNF. Vedolizumab was discontinued less frequently than anti-TNF. Patients on vedolizumab had higher rates of endoscopic remission and response.

Telemedicine has shown promise in inflammatory bowel disease (IBD). The objective of this study was to compare disease activity and quality of life (QoL) in a 1 year randomized trial of IBD patients receiving telemedicine versus standard care. Patients with worsening symptoms in the prior 2 years were eligible for randomization to telemedicine (monitoring via texts EOW or weekly) or standard care. The primary outcomes were the differences in change in disease activity and QoL between the groups; change in health care utilization among groups was a secondary aim. 348 participants were enrolled (117 control group, 115 TELE-IBD EOW, and 116 TELE-IBD weekly). 259 (74.4%) completed the study. Age was 38.9 ± 12.3 years, 56.6% were women, 91.9% were Caucasian, 67.9% had Crohn’s disease (CD) and 42.5% had active disease at baseline. In CD, all groups experienced a decrease in disease activity (control −5.2 ± 5.0 to 3.7 ± 3.6, TELE-IBD EOW 4.7 ± 4.1 to 4.2 ± 3.9, and TELE-IBD weekly 4.2 ± 4.2 to 3.2 ± 3.4, p

Background Depression is common in patients with inflammatory bowel disease (IBD) and is known to be associated with poor adherence in the usual care setting. In the last decade, there has been an increase in the use of information technology (IT) for the delivery of IBD care, but the association between depressive symptoms (DS) and adherence to self-testing in this context is not known. We aimed to investigate this association among IBD patients managed via a text messaging-based telemedicine system. Methods This was a prospective study of participants in the 2 intervention arms of the Telemedicine for Patients with IBD (TELE-IBD) trial. Depressive symptoms were measured at baseline, and then participants received periodic text messages to initiate IBD-specific self-testing. Treatment plans were similarly conveyed, and adherence to self-testing was evaluated at the end of 1 year. Regression analyses were performed, and age-stratified models were constructed to evaluate for effect modification. Results Of the 193 study participants, 48% had DS at baseline. Overall, there was no significant association between DS and adherence to self-testing. However, upon stratification by age, adherence increased with depressive symptoms in those that were 40 years and younger (P = 0.02), but there was no association between depressive symptoms and adherence in the older group (P = 0.53). Conclusions Younger IBD patients with DS have high adherence when managed in a text messaging-based telemedicine program. Telemedicine interventions have the potential to improve health outcomes in this demographic-a group that is often thought to be difficult to manage due to nonadherence.

Background Effective treatments are available for patients with inflammatory bowel disease (IBD); however, suboptimal outcomes occur and are often linked to patients’ limited disease knowledge. The aim of this analysis was to determine if delivery of educational messages through a telemedicine system improves IBD knowledge. Methods TELEmedicine for Patients with IBD (TELE-IBD) was a randomized controlled trial with visits at baseline, 6 months, and 12 months; patient knowledge was a secondary aim of the study. Patients were randomized to receive TELE-IBD every other week (EOW), weekly (TELE-IBD W), or standard of care. Knowledge was assessed at each visit with the Crohn’s and Colitis Knowledge (CCKNOW) survey. The primary outcome was change in CCKNOW score over 1 year compared between the TELE-IBD and control groups. Results This analysis included 219 participants. Participants in the TELE-IBD arms had a greater improvement in CCKNOW score compared with standard care (TELE-IBD EOW +2.4 vs standard care +1.8, P = 0.03; TELE-IBD W +2.0 vs standard care +1.8, P = 0.35). Participants with lower baseline CCKNOW scores had a greater change in their score over time (P < 0.01). However, after adjusting for race, site, and baseline knowledge, there was no difference in CCKNOW score change between the control and telemedicine arms. Conclusions Telemedicine improves IBD-specific knowledge through text messaging, although the improvement is not additive with greater frequency of text messages. However, after adjustment for confounding variables, telemedicine is not superior to education given through standard visits at referral centers. Further research is needed to determine if revised systems with different modes of delivery and/or frequency of messages improve disease knowledge.

Background & Aims In women with inflammatory bowel diseases (IBDs), exposure to immunomodulator or biologic therapy has not been associated with adverse events during pregnancy or outcomes of newborns. We investigated whether exposure of patients to these agents during pregnancy affects serologic responses to vaccines in newborns. Methods We collected data from the Pregnancy in IBD and Neonatal Outcomes registry, which records outcomes of pregnant women with diagnosis of IBD receiving care at multiple centers in the United States, from 2007 through 2016. Serum samples collected from infants at least 7 months old were analyzed for titers of antibodies to Haemophilus influenzae B (HiB) or tetanus toxin; mothers completed a survey of vaccine practices and outcomes from July 2013 through October 2016. Umbilical cord blood samples from 33 infants were assayed for concentration of biologic agents. Vaccination response was compared between infants born to mothers exposed to biologic therapy (infliximab, adalimumab, certolizumab pegol, golimumab, natalizumab, vedolizumab, or ustekinumab—either as a single agent or in combination with an immunomodulator, at any time between conception and delivery) and infants born to unexposed mothers. Results A total of 179 women completed the vaccine survey (26 biologic unexposed, 153 exposed to a biologic agent). We found no significant difference in proportions of infants with protective antibody titers against HiB born to exposed mothers (n = 42, 71%) vs unexposed mothers (n = 8, 50%) ( P = .41). We also found no difference in the proportion of infants with protective antibody titers to tetanus toxoid born to exposed mothers (80%) vs unexposed mothers (75%) ( P = .66). The median concentration of infliximab in cord blood did not differ significantly between infants with vs without protective antibody titers to HiB ( P = .30) or tetanus toxoid ( P = .93). Mild reactions were observed in 7/40 infants who received rotavirus vaccine and whose mothers had been exposed to biologic therapies. Conclusions Vaccination of infants against HiB and tetanus toxin, based on antibody titers measured when infants were at least 7 months old, does not appear to be affected by in utero exposure to biologic therapy.

BACKGROUND Inflammatory bowel disease (IBD) is associated with altered body composition, such as low muscle mass, which affects clinical outcomes. Body composition changes in overweight patients with IBD are less understood. The study aim was to determine the prevalence of sarcopenic overweight and obese patients in a cohort of patients with IBD starting new anti-tumor necrosis factor-α therapy and examine differences in response. METHODS This is a retrospective review of patients with IBD starting a new anti-tumor necrosis factor-α medication that had computed tomography within 3 months of initiation. L3 vertebral slice was used for segmentation of body composition and identification of sarcopenia. CRP, ESR, Harvey Bradshaw Index, albumin, 25-OH vitamin D, and body mass index at anti-tumor necrosis factor-α initiation and at 6 months were collected. Outcomes included hospitalization, need for surgery, or new biological medication. RESULTS Ninety patients were studied. Forty-one of ninety (45%) were sarcopenic; of these, 17 (41.5%) had a normal body mass index and 8 (19.5%) were overweight/obese. More men were sarcopenic (68% versus 32%, P < 0.001). CRP was higher and albumin lower in sarcopenic subjects. Sarcopenia did not predict outcomes in the cohort but was the only significant predictor of need for surgery in overweight and obese subjects (P = 0.002). CONCLUSIONS Almost half of our cohort was sarcopenic. Most of these patients are normal or overweight and would not be identified as malnourished by traditional measures. Sarcopenia was a predictor of surgery in patients with a body mass index ≥ 25. Identification of sarcopenia has implications for medical nutrition therapy as typically efforts are focused on underweight patients.

Background Ustekinumab was approved for moderate and severe Crohn’s disease (CD) in 2016, but little is known about long-term outcomes. Methods A retrospective study evaluated all patients with CD treated with ustekinumab, including patients with reinduction. C-reactive protein (CRP), Harvey-Bradshaw Index (HBI), Short Inflammatory Bowel Disease (SIBDQ), and endoscopy outcomes were collected prospectively. Results Ninety-six patients received ustekinumab, resulting in improvement in CRP, HBI, and SIBDQ scores with 68% endoscopic improvement/remission. Thirty-four patients underwent reinduction, resulting in improved HBI and CRP. Conclusions Ustekinumab in refractory CD results in significant clinical and endoscopic improvement and reinduction may be a viable option to recapture response., Lay Summary This study shows that ustekinumab can be used to improve symptoms and disease markers in patients with severe Crohn disease who have failed prior medications. The study also demonstrates that reinduction can help regain response if needed.

Background Depression is common in patients with inflammatory bowel disease (IBD) and contributes to poor quality of life (QoL). The use of information technology for the remote management of patients with IBD is growing, but little is known about its impact on depressive symptoms (DS) and QoL. We aimed to evaluate the impact of telemedicine on DS and generic QoL in IBD patients. Methods We analyzed data from the Telemedicine for Patients with IBD (TELE-IBD) study. During this 12-month clinical trial, patients were randomized to receive text message-based telemedicine weekly (TELE-IBD W), every other week (TELE-IBD EOW), or to standard care. Depressive symptoms and QoL were assessed over time with the Mental Health Inventory 5 (MHI-5) and the Short Form 12 (SF-12), respectively. We compared the change in MHI-5 and SF-12 (with separate physical (PCS) and mental component summary (MCS) scores) between the study arms. Results A total of 217 participants were included in this analysis. After 1 year, there was no significant difference in the change in MHI-5 (TELE-IBD W +3.0 vs TELE-IBD EOW +0.7 vs standard care +3.4; P = 0.70), MCS (TELE-IBD W +1.4 vs TELE-IBD EOW +1.0 vs standard care +2.5; P = 0.89), and PCS scores (TELE-IBD W +0.4 vs TELE-IBD EOW +0.6 vs standard care +3.7; P = 0.06) between the groups. Conclusions Text message-based telemedicine does not improve DS or QoL when compared with standard care in IBD patients treated at tertiary referral centers. Further studies are needed to determine whether telemedicine improves DS or QoL in settings with few resources., Lay Summary This study showed that, in patients with inflammatory bowel disease, the use of information technology to deliver care via text messaging did not improve depressive symptoms or quality of life when compared with usual healthcare.

Introduction The need to rapidly implement telehealth at large scale during the COVID-19 pandemic led to many patients using telehealth for the first time. We assessed the effect of structured pre-visit preparatory telephone calls on success of telehealth visits and examined risk factors for unsuccessful visits. Methods A retrospective cohort study was carried out of 45,803 adult patients scheduled for a total of 64,447 telehealth appointments between March and July 2020 at an academic medical center. A subset of patients received a structured pre-visit phone call. Demographic factors and inclusion of a pre-visit call were analysed by logistic regression. Primary outcomes were non-completion of any visit and completion of phone-only versus audio-visual telehealth visits. Results A pre-visit telephone call to a subset of patients significantly increased the likelihood of a successful telehealth visit (OR 0.54; 95% CI: 0.48–0.60). Patients aged 18–30 years, those with non-commercial insurance or those of Black race were more likely to have incomplete visits. Compared to age 18–30, increasing age increased likelihood of a failed video visit: 31–50 years (OR 1.31; 95% CI: 1.13–1.51), 51–70 years (OR 2.98; 2.60–3.42) and >70 years (OR 4.16; 3.58–4.82). Those with non-commercial insurance and those of Black race (OR 1.8; 95% CI 1.67–1.92) were more likely to have a failed video visit. Discussion A structured pre-call to patients improved the likelihood of a successful video visit during widespread adoption of telehealth. Structured pre-calls to patients may be an important tool to help reduce gaps in utilization among groups.

The prevalence of depression is high in patients with Crohn’s Disease (CD). We examined the influence of affective-cognitive symptoms of depression on the risk of exacerbation of CD.

BackgroundStudies suggest that there is a temporal relationship between depression and Crohn’s disease (CD) activity. However, these studies assumed a unidirectional relationship and did not examine the possibility of reverse causality and the risk of a spurious association due to the overlap of symptoms underlying the depression–CD relationship. We evaluated the existence of reverse causality reflected in a possible bidirectional relationship between patient-reported CD activity and an affective–cognitive dimension of depression.MethodsWe studied 3307 adult volunteers with a self-reported diagnosis of CD who completed a baseline survey that included demographics, CD activity, and an affective–cognitive index of depression. Crohn’s disease status and the affective–cognitive index of depression were also measured 6 and 12 months after the baseline evaluation. We used structural equation models to evaluate whether the effect of depression on future CD activity is stronger than the effect of CD activity on future depression. We calculated the likelihood that each of these hypotheses is supported by the data and calculated the likelihood ratio to provide a relative measure of which hypothesis best accounts for the data.ResultsThe results of the informative hypothesis testing showed the most support for the hypothesis stating that an affective–cognitive dimension of depression is a stronger predictor of patient-reported CD activity than the converse.ConclusionsThe hypothesis that an affective–cognitive dimension of depression predicts patient-reported exacerbation of CD is 218 times more likely to account for the data than the converse.

INTRODUCTION: Limitations in inflammatory bowel disease (IBD) care necessitate greater patient activation and self-efficacy, measures associated with positive health outcomes. METHODS: We assessed change in patient activation and general self-efficacy from baseline to 12 months through our TELEmedicine for IBD trial, a multicenter, randomized controlled trial consisting of a web-based monitoring system that interacts with participants via text messaging. A total of 222 adults with IBD who had experienced an IBD flare within 2 years prior to the trial were randomized into either a control arm that received standard care (SC) or an intervention arm that completed self-testing through the TELE-IBD system every other week (EOW) or weekly (W). RESULTS: Changes in self-efficacy scores were not significantly different between control and experimental groups. Patient activation scores were significantly different between standard care and the TELE-IBD EOW group only (p = 0.03). CONCLUSIONS: Use of remote monitoring did not improve self-efficacy or patient activation compared to routine care.

BACKGROUND Managing patients with IBD who are refractory or have contraindications to standard therapies is challenging. Many will lose response, become intolerant to treatment, or develop infections with contraindication for immunosuppression. Therefore, alternative therapies, such as the use of intravenous immunoglobulin (IVIg), could be used to manage patients in these difficult cases. METHODS Data were extracted retrospectively from the electronic medical records at Vanderbilt University on patients with IBD who received IVIg (February 2011-June 2013). Patients were treated with IVIg 0.4 g·kg·d for 3 consecutive days and then 0.4 g/kg once monthly. The dose was increased to 0.4 g/kg biweekly for loss of response or partial response. Clinical response was defined as decreasing the Harvey-Bradshaw Index ≥3 points or improvement in C-reactive protein >25%. Clinical remission was defined as Harvey-Bradshaw Index score

Biomarkers are needed in inflammatory bowel disease (IBD) to help define disease activity and identify underlying pathogenic mechanisms. We hypothesized that serum metabolomics, which produces unique metabolite profiles, can aid in this search.The aim of this study was to characterize serum metabolomic profiles in patients with IBD, and to assess for differences between patients with ulcerative colitis (UC), Crohn's disease (CD), and non- IBD subjects.Serum samples from 20 UC, 20 CD, and 20 non-IBD control subjects were obtained along with patient characteristics, including medication use and clinical disease activity. Non-targeted metabolomic profiling was performed using ultra-high performance liquid chromatography/mass spectrometry (UPLC-MS/MS) optimized for basic or acidic species and hydrophilic interaction liquid chromatography (HILIC/UPLC-MS/MS).In total, 671 metabolites were identified. Comparing IBD and control subjects revealed 173 significantly altered metabolites (27 increased and 146 decreased). The majority of the alterations occurred in lipid-, amino acid-, and energy-related metabolites. Comparing only CD and control subjects revealed 286 significantly altered metabolites (54 increased and 232 decreased), whereas comparing UC and control subjects revealed only 5 significantly altered metabolites (all decreased). Hierarchal clustering using significant metabolites separated CD from UC and control subjects.We demonstrate that a number of lipid-, amino acid-, and tricarboxylic acid (TCA) cycle- related metabolites were significantly altered in IBD patients, more specifically in CD. Therefore, alterations in lipid and amino acid metabolism and energy homeostasis may play a key role in the pathogenesis of CD.

INTRODUCTION: Varenicline doubles cessation over nicotine replacement therapy (NRT) patch for “normal,” but not “slow,” nicotine metabolizers, as assessed by the nicotine metabolite ratio (NMR). Metabolism-informed care (MIC) could improve outcomes by matching normal metabolizers with non-nicotine medication (e.g., varenicline) and slow metabolizers with NRT patch. METHODS: We conducted a feasibility randomized controlled trial of MIC versus guideline based care (GBC) among 81 outpatient adult daily smokers with medical comorbidity. Participants reported perceptions of MIC, underwent blood draw for NMR, and received expert cessation counseling. For MIC participants, medication selection was informed by NMR result (normal (≥0.31) vs. slow (< 0.31)). The primary outcome was MIC feasibility, reflected by attitudes toward MIC and by match rates between NMR and medication. Secondary endpoints (cessation confidence, medication use, smoking status) were assessed over 6 months to inform future studies. RESULTS: Participants were median age 53 years, 46% female, 28% black, and ~90% endorsed MIC. Despite high varenicline prescription rates (~60%) in both arms, NMR-medication matching was higher in MIC (84%) versus GBC (58%) participants (p=0.02); unadjusted odds ratio (OR) 3.67, 95% confidence interval [1.33, 11.00; p-value=0.02]. Secondary endpoints were similar at 1, 3, and 6 months. CONCLUSIONS: MIC, an NMR-based precision approach to smoking cessation, was acceptable to 90% of smokers and improved NMR-medication match rates more than 3-fold compared to GBC, even with generally high use of varenicline. These data support the feasibility of MIC, which could maximize efficacy of smoking cessation medication while minimizing side effects and cost. IMPLICATIONS: Among treatment-seeking daily smokers with medical comorbidity, most viewed metabolism-informed care (MIC), guided by the nicotine metabolism ratio (NMR), favorably, and were willing to accept MIC-guided medication. Compared to GBC participants (58%), more MIC participants (84%) were prescribed NMR-matched medication (i.e., normal metabolizers received varenicline; slow metabolizers received NRT patch). MIC increased the odds of optimized matching between NMR and medication more than 3-fold over GBC. Because the number needed to treat (NNT) to help one normal metabolizer quit smoking is only 4.9 for varenicline versus 26 for patch, broad implementation of MIC will improve drug efficacy in normal metabolizers as well as minimize side effects in slow metabolizers.

Background Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD. Objectives The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD. Search methods We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index. Selection criteria Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention. Data collection and analysis Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria. Main results Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence). Authors' conclusions Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.

Noncompliance in use of anti-tumor necrosis factor (anti-TNF) therapy in patients with moderate-to-severe inflammatory bowel disease (IBD) can be a factor in medication failure. Few studies have evaluated the contribution of depressive symptoms to medication noncompliance in anti-TNF therapies. A retrospective chart review was performed in a single-center tertiary care IBD center for patients with Crohn’s disease and ulcerative colitis starting anti-TNF therapy over a 2-year period. Medication noncompliance was defined as interruption of medication (not filling anti-TNF prescription if injectable or not getting infliximab infusion for 30 days beyond needed date for continuation) due to patient-driven circumstances. Depressive symptoms were evaluated at baseline using the well-validated Patient Health Questionnaire-9 (PHQ-9), with PHQ-9 ≥ 10 indicative of at least moderate depressive symptoms. Statistical analysis was performed using Cox proportional hazards regression controlling for age, sex, psychiatric history, and disease. A total of 246 patients (75 with ulcerative colitis, 171 with Crohn’s disease) were started on anti-TNF therapy. Seventy-nine patients (32%) had a prior psychiatric diagnosis reported in the medical record. Thirty-three patients (13%) were noncompliant in follow-up. Sixty patients (24%) had at least moderate depressive symptoms at baseline (PHQ ≥ 10). Depressive symptoms at baseline were significantly associated with noncompliance in follow-up (hazards ratio 2.28, CI 1.1–4.6, p

Background The safety of inflammatory bowel disease (IBD) medications during lactation is of significant interest and relevance to female patients of childbearing potential. Available data regarding the safety and transfer of biologic agents via breast milk are limited to case reports. Vedolizumab has a well-established, positive benefit-risk profile in adult IBD patients. Literature data show that vedolizumab is detectable in human milk. Methods A prospective, postmarketing, phase 4, open-label, milk-only lactation study was conducted to assess vedolizumab concentrations in breast milk from lactating women with IBD who were on an established vedolizumab maintenance regimen (300 mg intravenous [IV] every 8 weeks [Q8W] or an alternative dose frequency). Maternal milk samples were serially collected throughout the dosing interval on Days 1 (predose and 1 h after the end of vedolizumab infusion), 4, 8, 15, 29, and 57 to allow the estimation of drug excreted in milk relative to the maternal dosage. Maternal safety data were also collected. Results A total of 11 patients were enrolled in the study. Vedolizumab was detectable in the majority of milk samples collected on Days 1 and 57, and in all samples collected at other time points. Following receipt of vedolizumab 300 mg IV on Day 1, the vedolizumab milk concentration increased with a median time to peak concentration (Cmax) of 3–4 days, and subsequently decreased exponentially. For the 9 patients on the Q8W regimen, median Cmax was 0.213 µg/ml (range, 0.098–0.561 µg/ml); the geometric mean daily infant dosage, calculated using average concentration over 8-week dosing interval (0.13 µg/ml), was 0.02 mg/kg/day with a corresponding geometric mean percentage of maternal dosage consumed in breast milk by infants of 21%. The maternal safety profile was acceptable and similar to that observed in previous adult studies. Leveraging the mean trough serum concentration of 11.2 µg/ml from historical studies of vedolizumab, the ratio of mean milk concentration (trough, 0.05 µg/ml; peak, 0.25 µg/ml) to serum concentration was approximately 0.4%-2.2%, which is consistent with published data for vedolizumab and comparable with several other monoclonal antibody therapeutics for IBD. Published vedolizumab studies also showed no increase in general or gastrointestinal tract infections in the infants exposed to vedolizumab in breast milk, and exposed infants reached their acceptable development milestones through up to 10 months of follow-up. Conclusion Vedolizumab was found to be present in human breastmilk at a low level. The impact of vedolizumab IV administration during breastfeeding is expected to be minimal.

Recent research suggests a relationship of inflammatory bowel disease (IBD) and depression. Our objective was to evaluate for improvement of depressive symptoms with treatment of IBD using immunosuppressive medications.A retrospective study of consecutive patients with IBD started on immunosuppressive agents [anti-tumor necrosis factor (anti-TNF) or immunomodulator therapy] was conducted. Patients were evaluated if disease activity indices using Harvey Bradshaw Index for Crohn's disease (CD) and Simple Clinical Colitis Disease Activity Index for ulcerative colitis (UC) and depressive indices using Patient Health Questionnaire-9 (PHQ-9) scores were obtained before and at least 30 days after initiation of therapy.Sixteen patients with UC and 53 patients with CD (all with active disease symptoms) were evaluated over a 60 day median follow-up evaluation (range 30, 140 days). Twenty-two patients started on immunomodulator therapy, and 47 patients started on anti-TNF therapy. Crohn's disease patients had significantly decreased PHQ-9 scores at follow-up [median 9 (range 3, 14) to 4 (1, 8)], with significant decreases only in those started on anti-TNF therapy. Changes in PHQ-9 and CRP were correlated (ρ = 0.38, p0.05). In patients with UC, PHQ-9 scores [5 (3, 9) to 2 (0, 5)] were significantly decreased. Percentage at risk of moderate to severe depression (PHQ-9 scores ≥10) was lower after treatment [Crohn's disease 51-18 % (p0.05), ulcerative colitis 18-0 %].Depressive scores decreased significantly in patients with IBD treated with immunosuppressive therapy and the number at risk for moderate to severe depression improved significantly.