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ObjectiveActive inflammatory bowel disease (IBD) during pregnancy may require the use of corticosteroids. The aim of this study was to investigate the impact of in utero corticosteroid exposure on adverse pregnancy outcomes, congenital malformations, infections and neurocognitive development among offspring of mothers with IBD.DesignUsing the prospective Pregnancy in Inflammatory Bowel Disease and Neonatal Outcomes registry, data were collected at each trimester, delivery; and in the 12 months post partum. Bivariate statistics and multivariate logistic regression models compared pregnancy outcomes by corticosteroid exposure.ResultsA total of 1490 mothers with IBD were enrolled, with 1431 live births recorded. Corticosteroid use was associated with increased risk of preterm birth, small for gestational age, low birth weight (LBW), intrauterine growth restriction and neonatal intensive care unit (NICU) admission. On adjusted multivariate models, corticosteroid use was associated with preterm birth (OR 1.79, 95% CI 1.18 to 2.73), LBW (OR 1.76, 95% CI 1.07 to 2.88) and NICU admission (OR 1.54, 95% CI 1.03 to 2.30). Late corticosteroid use (second and/or third trimester) was associated with serious infections at 9 and 12 months (4% vs 2% and 5% vs 2%, respectively, p=0.03 and p=0.001). There were five newborns with in utero corticosteroid exposure born with orofacial clefts versus one without corticosteroid exposure. Developmental milestones were similar across corticosteroid exposure groups.ConclusionIn this prospective pregnancy registry, offspring of women exposed to corticosteroids during pregnancy were more likely to have adverse pregnancy outcomes. This emphasises the importance of controlling disease activity before and during pregnancy with steroid-sparing therapy.

BACKGROUND Tofactinib is a JAK inhibitor that targets mainly JAK 1 and JAK3 approved to treat Ulcerative Colitis (UC) in 2018. The JAK inhibitor Upadacitinib (upa) was recently approved to treat UC in March 2022 and has increased selectivity for JAK1. The relative efficacy and safety of these two JAK inhibitors is not presently clear. An important clinical question is whether patients who have not responded or lost response to tofacitinib will have a reasonable likelihood of response with upadacitinib. AIM To determine whether patients previously exposed to tofacitinib would benefit from treatment with upa. METHODS We identified adult patients at our center with active UC who had previously been treated with tofacitinib who were started on upa in the spring of 2022. Pre- and post- upa characteristics were recorded including demographic information, prior treatments, hemoglobin (hgb), albumin (alb), C-reactive protein (CRP), and partial Mayo score (pMS). Primary end points evaluated were clinical response (decrease in pMS >2), and clinical remission (pMS < 2). Secondary endpoints included serious adverse events, steroid use at time of follow up, and normalization of CRP, hgb and alb. IRB approval was obtained for the study. RESULTS A total of 3 patients were identified. All patients were given upa 45 mg daily for 8 weeks followed by 30 mg daily for maintenance. Median follow up time was 10 weeks (range 10-11 weeks). All three patients achieved the primary endpoints of clinical response and remission with pMS values of 0 at time of follow up. Patients 1 and 2 were concurrently started on a prednisone taper when initiating upa and were no longer on prednisone at time of follow up. Patients 1 and 2 had normalization of their CRP values, patient 3 only had a pre-upa CRP value available and that was 0. See table 1 for data on hgb and alb levels. Patient 1 had a pre-upa endoscopic mayo score of 3, while patients 2 and 3 had pre-upa endoscopic mayo scores of 2. No patient had post-upa endoscopic evaluation at time of follow up. No patient had any serious adverse events. CONCLUSIONS In this small case-series, use of upadacitinib in patients previously treated with tofacitinib was safe and effective in achieving clinical remission.

INTRODUCTION Mirikizumab, an anti-IL23p19 antibody, has demonstrated safety and efficacy versus placebo across clinical remission, symptomatic remission, and endoscopic and histologic endpoints in patients with moderately-to-severely active ulcerative colitis (UC) in a Phase 3, double-blind, 12-week induction study (LUCENT-1/NCT03518086) and 40-week maintenance study (LUCENT-2/NCT03524092). Here, we examine the relationship between bowel urgency (BU) clinically meaningful improvement (CMI) and BU remission with rectal bleeding (RB) remission and stool frequency (SF) remission (Table 1 for definitions). METHODS Patients in LUCENT-1 (N=1281) were randomly assigned 3:1 to receive intravenous mirikizumab 300mg or placebo every four weeks (Q4W) for a total of 12 weeks. Patients who achieved clinical response to mirikizumab by Week 12 of LUCENT-1 (N=544) were re-randomized 2:1 to subcutaneous mirikizumab 200mg or placebo Q4W for 40 weeks in LUCENT-2 (maintenance study). Patients recorded their BU severity in the previous 24 hours using an 11-point Urgency Numeric Rating Scale (UNRS; 0=no urgency to 10=worst possible urgency) in an electronic daily diary. Weekly scores were averaged for patients with at least 4 of 7 days of complete diary data. BU remission was defined as UNRS score of 0 or 1, and BU CMI was defined as ≥3-point decrease in UNRS score compared to baseline. For patients who achieved clinical response at the end of induction, analyses were repeated for the end of maintenance at Week 40 (for 52 weeks of continuous treatment). Patients with UNRS RESULTS A total of 1087 patients reported a baseline UNRS score ≥3. Patients achieving BU CMI had significantly higher rates of RB remission and SF remission at both Week 12 and Week 40 compared with patients not achieving these outcomes (all p CONCLUSION A higher proportion of patients enrolled in LUCENT-1 and -2 who achieved BU CMI and BU remission achieved RB remission and SF remission. These results support that the symptom of bowel urgency is an important marker of UC disease activity that is related to and distinct from other commonly accepted symptoms of active UC.

BACKGROUND Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract often requiring long-term medical therapy. While adherence to IBD therapies is associated with improved clinical outcomes, overall adherence is poor with reports demonstrating adherence rates ranging from 40% to 80%. Consequently, there is a critical need to develop interventions that monitor adherence in-real time and identify reasons for non-adherence to support clinical teams in initiating effective interventions. Recently, electronic- and virtual-based platforms have been developed to routinely monitor adherence and guide appropriate interventions. A novel remote therapeutic monitoring (RTM) technology, the TapptTM digital health system, has been developed to monitor real-time medication adherence patterns through smart label technologies, capture patient reported outcomes (PROs) and barriers to care, and process patient data through algorithms that trigger personalized digital and human touchpoints between clinical visits. Such digital health solution enables care teams to proactively identify and mitigate nonadherence and worsening clinical outcomes. OBJECTIVE We propose a 12-month, multicenter, randomized, controlled trial to assess the effectiveness of TapptTM digital health system on adherence, clinical outcomes, and healthcare utilization among patients diagnosed with IBD starting a new oral or subcutaneous therapy. METHODS Specifically, we will (Aim 1) compare adherence as measured by the Medication Possession Ratio (MPR) in participants using the RTM compared to standard of care and (Aim 2) compare clinical outcomes and healthcare utilization in participants using the RTM compared to standard of care. RESULTS We anticipate starting recruitment in August 2022. CONCLUSIONS Effective medication adherence monitoring and intervention programs need to be cost-efficient, pose little to no burden to the patient, be unobtrusive, record reliable data in real-time, and provide actionable insights to the healthcare team. We anticipate the TapptTM digital health system to improve the MPR, clinical outcomes, and healthcare utilization compared to standard of care. CLINICALTRIAL NCT05316584

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Lay Summary Dysplasia surveillance practice varies widely among high-volume inflammatory bowel disease providers. We surveyed high-volume inflammatory bowel disease providers about practice patterns to detect dysplasia. Regular use of dye-based chromoendoscopy was reported by 20%, virtual chromoendoscopy by 27%, and random biopsies by 58%.

Background & Aims Despite highly effective therapies, many children develop medically refractory ulcerative colitis (UC) and undergo proctocolectomy with ileal pouch anal anastomosis (IPAA). There is little real world evidence regarding IPAA outcomes in pediatric UC patients. We sought to determine the risk of pouchitis, recurrent pouchitis, and change in diagnosis to Crohn’s disease (CD) within two years of IPAA surgery among pediatric patients with UC using a large, geographically diverse insurance claims database. Methods Within the IQVIA Legacy PharMetrics Adjudicated Claims Database, we identified pediatric patients (age Results A total of 68 patients with an IPAA with at least two years of continuous health plan enrollment following surgery were identified. Among all patients undergoing surgery, the median age was 15 years (interquartile range 11.5–16), with 29 (43%) female patients. In the first 2 years following IPAA, the cumulative incidence of pouchitis was 54%. Characteristics and prior medical treatments in patients without pouchitis and with ≥ one episode of pouchitis were similar (Table 1). The cumulative incidence of recurrent pouchitis during this period was 22%. The cumulative incidence of a new diagnosis of CD in the two years after IPAA for UC was 9%. Conclusions In a geographically diverse cohort from the United States, 54% of pediatric patients undergoing proctocolectomy with IPAA for UC developed pouchitis within the first two years after surgery. Furthermore, 9% had a change in diagnosis to CD. These data indicate that for many pediatric UC patients, surgery is non-curative and patients continue to have a substantial burden of illness. Future efforts should attempt to identify novel, actionable, predictors of pouchitis in this population.

Background The number of older adults with inflammatory bowel diseases (IBD) is increasing. Older adults with IBD are less likely to receive effective immunosuppression. We aimed to determine efficacy and safety of biologic therapies in older adults with IBD. Methods We conducted a retrospective cohort study using an active comparator, new user design in a 20% random sample from the 50 state Medicare claims database between May 2014 and December 2018. We included patients who initiated vedolizumab or an anti-tumor necrosis factor (TNF)-α agent (infliximab, adalimumab, golimumab or certolizumab) following 12-months of continuous enrollment in Medicare fee-for-service Parts A/B/D without either study drug. Patients were required to be ≥65 years old and have ≥2 international classification of disease (ICD) codes of Crohn’s disease (CD) or ulcerative colitis (UC). We excluded patients who received other biologic therapies and/or those who had ≥2 codes for other immunologic conditions. Pertinent co-variates included were age, sex, race Charlson Co-morbidity Index (CCI), predicted probability of frailty, healthcare utilization and baseline IBD medications. The outcomes of interest were hospitalizations, IBD-related surgery and new corticosteroid use ≥ 60 days after drug initiation. We described the study population, assessed health care utilization and use of other IBD medications. We estimated crude incidence rates and hazard ratios (HR) adjusted for the covariates using standardized mortality ratio (SMR) weights. Results We identified 488 vedolizumab users and 2,213 anti-TNF users. The median age was 72 years in the vedolizumab cohort and 71 years in the anti-TNF cohort; 12% of both cohorts were aged ≥80 years. Differences in the two cohorts existed with regards to sex, race, baseline healthcare utilization and IBD-related medications, but all the baseline differences were balanced by weighting measured by a standardized mean difference (SMD) Conclusions In this large, retrospective cohort study of older IBD patients who were new users of vedolizumab and anti-TNF agents, we found that older patients initiated on vedolizumab were significantly less likely to have an infection-related hospitalization. However, there were no significant differences in IBD-related hospitalizations, IBD-related surgery or corticosteroid use after biologic induction.

Background and Aims There are currently several recruitment challenges in randomized controlled trials (RCT) for inflammatory bowel disease (IBD) which prolong the drug approval process and affect the generalizability of study results. The purpose of this study is to characterize individuals who participate in IBD RCTs and identify factors which could influence future recruitment strategies. Methods We performed a cross-sectional study within the IBD Partners cohort comparing patients with current or prior participation in an interventional randomized controlled trial (RCT) of a medical therapy for IBD to those without any RCT participation. Bivariate statistics were used to compare RCT participation by IBD subtype and by other demographic and disease characteristics, and predictive modeling was used to identify factors predictive of RCT participation. We calculated the percent of the cohort that participated an in RCT during each calendar year from 2011–2018 and Clinicaltrials.gov was accessed to determine the number of active RCTs for IBD therapies per year during that same period. Results A total of 14,747 patients with IBD were included in the analysis and 1,116 (7.6%) reported RCT participation at any time. Demographic factors predictive of RCT participation (Table 1) included following at an academic institution (OR=1.8; 95%CI: 1.51–2.04) and age 36–75 (OR=1.6; 95%CI: 1.43–1.87). Patients with Crohn’s disease (CD) were more likely to participate than those with ulcerative colitis (UC) (OR=1.5; 95%CI: 1.35–1.77). Patients with more severe disease were more likely to participate, including those with prior IBD-related hospitalization (OR=2.6; 95%CI: 2.19–2.99), IBD-related surgery (OR=2.5; 95%CI: 2.24–2.87), biologic exposure (OR=3.2; 95%CI: 2.76–3.65), and “Poor” or worse quality of life (OR=1.7; 95%CI: 1.45–1.93). Steroid-free remission was associated with lower likelihood of RCT participation (OR=0.6; 95%CI: 0.53–0.70). While the number of active RCTs for IBD more than doubled between 2011 and 2018, RCT participation rates during that same time period decreased from 1.1% to 0.7% of the cohort (Figure 1). Conclusions RCT participation rates declined within this cohort between 2011–2018. Groups underrepresented in RCTs for IBD included younger patients, patients followed in community settings, and patients with more mild disease. The non-RCT group had mean sCDAI and SCCAI scores that did not meet remission thresholds, demonstrating populations in need of alternate therapies for whom clinical trials could be an option. Given anti-TNF exposure rates in this national cohort, studies should focus on anti-TNF failure populations. Investigators should make every effort to offer RCTs to all patients and network with community providers to increase awareness of RCTs.

Background While restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the preferred surgical approach in patients with medically refractory ulcerative colitis (UC) or UC-related dysplasia, a significant proportion of patients develop pouchitis and/or report decreased health related quality of life (HRQOL) at some point after IPAA. We designed this study to 1) evaluate the association between recently reported pouchitis and specific Patient-Reported Outcome Measurement Information System (PROMIS) domains (anxiety, depression, fatigue, pain interference, sleep disturbance, and social role satisfaction) and HRQOL as assessed by the Cleveland Global Quality of Life (CGQL) scale, and 2) describe the correlations between specific PROMIS domains and overall HRQOL. Methods IBD Partners is an internet-based cohort that collects patient reported survey data every 6 months. In patients who reported having an IPAA for UC, we performed cross sectional analyses to compare patient characteristics and patient reported outcomes among patients who reported pouchitis in the prior 6 months versus those without reported pouchitis. To identify the specific social, emotional, and physical domains most associated with HRQOL, we evaluated the correlations between PROMIS domains (measured in T-scores) and CGQL scores using Pearson’s test. Results Among 118 patients, 70 (59%) reported pouchitis in the prior 6 months. There were no significant differences in age, sex, race, or number of stages of IPAA between patients with and without recent pouchitis (Table 1). Patients with recent pouchitis were more likely to demonstrate higher levels of anxiety (53.8 vs. 48.5, p=0.005), depression (52.2 vs. 46.9, p=0.005), fatigue (55.8 vs. 47.8, p Conclusions Patients with recent pouchitis demonstrated a significant reduction in overall HRQOL as well as decrements in specific areas of social, emotional, and physical health. Among patients without pouchitis, strong correlations between multiple PROMIS domains and HRQOL were also demonstrated. These findings indicate that the PROMIS measures may be useful in assessing these areas of health that are clinically important after IPAA, allowing for tailored interventions in this population.

Background Individuals with IBD, comprised of Crohn’s disease (CD) and Ulcerative Colitis (UC), often have ongoing gastrointestinal symptoms that limit their ability to exercise. Importantly, exercise can help to maintain remission in individuals with IBD. Other positive health outcomes of exercise include improvement in quality of life, social and psychological well-being, weight maintenance, bone health, fatigue management and maintaining muscle mass and function. Unfortunately, many of the tools used to measure exercise are burdensome for clinical utility or are not applicable to the IBD population. The purpose of this secondary analysis was to determine if one question related to physical activity would capture exercise in adults with either UC or CD and those with active or inactive disease. Methods This study is a cross-sectional study using the data obtained from IBD Partners, an internet-based longitudinal cohort of adults ≥ 18 year of age living with IBD. This secondary analysis includes only those participants without a current ostomy or pouch, who completed demographic information, disease activity and exercise characteristics. Disease activity was measured via the simple clinical colitis activity index (SCCAI) for UC and the short Crohn’s disease activity index (sCDAI) for CD. Exercise was measured via the Godin Leisure -Time Activity Index (GLTA) questionnaire that assessed type of exercise and intensity for the past seven days. A separate measurement of physical activity included a single question: “How often did you participate in 1 or more physical activities of 20–30 minutes’ duration per session during your leisure time within the past 6 months?” measured via a 6-point ordered category item. Results A total of 8327 patients with IBD were included. Most (63%) of the participants had CD, and 54% were in remission. Majority of the participants were physically active based on GLTA scores (49.7%), and one question physical activity scores (62%; combined scores of 5 & 6). Polychoric correlation coefficient was computed, with a strong correlation between GLTA and the one question (r = 0.74, p < 0.001). Ordinal regression analysis between the one physical activity question and IBD type (UC vs CD) yielded higher odds of physical activity with UC (Odds ratio (OR)=1.2, 95% CI [1.11 -1.31], p < 0.0001). Similar results were noted with ordinal regression analysis between GLTA scores and UC;(OR=1.2, 95% CI [1.09 -1.3], p < 0.0001). Conclusions Both GLTA and the single question of physical activity were highly correlated. The ordinal regression results were comparable for both measures. Adoption of the single physical activity question may adequately reflect exercise status in IBD patients and reduce burden for clinical use. Further longitudinal studies are need to support the use of one question in measuring exercise in those with IBD.