Abstract Background Observational studies suggest non-white patients with inflammatory bowel disease (IBD) have worse clinical outcomes.1 There are limited data on whether race impacts response to biologic therapy. We therefore aimed to evaluate the efficacy of the tumor necrosis factor (TNF) antagonist golimumab comparing white to non-white participants, using individual participant level data from phase 2/3 randomized clinical trials of TNF antagonist therapy in ulcerative colitis (UC). Methods We conducted a pooled analysis of individual-level data from the induction and maintenance trials of golimumab in UC accessible through Yale University Open Data Access Project (YODA). There were insufficient non-white participants in infliximab studies accessible through YODA, precluding meaningful analysis. We analyzed patients in the placebo and treatment arms separately. Our primary outcome was clinical response and secondary outcomes were clinical remission and endoscopic healing according to clinical trial definitions. We compared white and non-white (defined as Black, Asian, or Other race) participants using multivariable logistic regression a priori adjusting for age, sex, treatment group, baseline Mayo score, immunomodulator and corticosteroid use. Effect estimates were expressed as adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Results A total of 1,006 participants were included in the induction trial (PURSUIT-SC; 18% non-white) and 783 participants in the maintenance trial (PURSUIT-M; 17% non-white). Non-white participants had significantly lower odds of week 6 clinical response (aOR 0.43, 95%CI 0.28–0.66), clinical remission (aOR 0.41, 95%CI 0.22–0.77) and endoscopic remission (aOR 0.48, 95%CI 0.30–0.74) compared to white participants (Figure). Non-white participants also had a lower adjusted odds of week 30 clinical response (aOR 0.64, 95%CI 0.40–1.01), clinical remission (aOR 0.45, 95%CI 0.28–0.74), and endoscopic remission (aOR 0.62, 95%CI 0.41–0.96). By week 54, the lower odds of these outcomes among non-whites were no longer statistically significant (Figure). Conclusion Non-white UC patients were less likely to achieve clinical response, clinical remission, and endoscopic healing with golimumab compared to white patients in these clinical trials. Further studies are needed to understand these differences and whether they are observed with other drugs or outside the context of clinical trials. Reference

Abstract Background Pivotal trials have shown that ustekinumab (UST) is effective in ulcerative colitis (UC). However, the population included in these trials do not always represent the cohort of patients treated in the “real world”. In this study, we aimed to describe the effectiveness and safety of UST in a clinical cohort of patients with UC Methods We performed a multi-center cohort study and included patients with active UC starting UST. Variables collected included demographics, previous and current UC medications, disease activity (measured using partial and endoscopic Mayo score [PMS and EMS]) at 8 weeks, 6 months and end of follow-up. We also abstracted UST drug level and anti-UST antibodies (AUA), albumin and C-reactive protein levels. Primary outcomes were clinical response at week 8 defined as a reduction of 3 points in the PMS or PMS<2. Secondary outcomes were clinical remission defined as a PMS <2 and endoscopic remission defined as a MES ≤1, and the development of an adverse event (AE) attributed to UST. Results Ninety-five patients were included with a median age of 42 years (IQR:32-57) and 53 (56%) were female. Median follow-up was 5 months (IQR:2.2-7.4). Only 4 (4.3%) were naïve to biologics or tofacitinib and 62 (66%) had previous exposure to at least 2 other biologics. No variables were found to be associated with response at week 8 (Figure 2). Those patients who responded at week 8 had higher median albumin levels vs those who did not (median of 4.4 [IQR: 4.1-4.6] vs 4.1 g/dL [IQR:3.8-4.3]; p=0.02). There were no differences in baseline CRP levels (1mg/dL [IQR:0.6-2.8] vs 0.6 mg/dL [0.3-1.5]; p=0.06). Among the 33 patients who had follow-up endoscopic assessment, 7 (21.2%) had achieved endoscopic remission and 4 (12%) achieved histologic remission. Median UST level was 4.1 mcg/ml (IQR:2.5-5.1) and no patients had detectable AUA. Five patients underwent colectomy (5.3%). Only 6 patients (6.6%) presented with an AE (all minor that included, rash, headaches, arthralgias and infection). Conclusion In a population enriched with refractory UC, UST was well tolerated and induce response and remission in a significant number of patients. The rate of response was lower in obese patients and those with extensive colitis but was not associated with previous exposure to biologics and/or tofacitinib. Larger studies with a longer follow-up are warranted. Figure 1: Rates of clinical response and remission in patients with UC receiving ustekinumab Figure 2: Association between several baseline characteristics and response to ustekinumab in UC

Background: Patients with IBD are ideal candidates for home-based remote monitoring care that is centered on enhanced symptom tracking and improved communication with care teams. The objective of this pragmatic randomized controlled trial is to determine the impact of the HealthPROMISE app in improving outcomes quality of care [QOC] and quality of life [QOL] as compared to a patient education app. Methods: Participants were randomized to either interventional (HealthPROMISE) or control (education app). All patients completed intake questionnaires assessing health literacy, disease severity, general health status, and demographic information. Patients in the HealthPROMISE arm were able to update their information and receive disease summary, QOC metrics and a graph trending QOL (SIBDQ) scores over time (https://clinicaltrials.gov/ct2/show/NCT02322307). Results: 320 patients were enrolled in the study at Mount Sinai Medical Center (MSMC) (see Table 1). Baseline assessment showed that fatigue and tension (anxiety) were the two most important drivers of poor quality of life. Patients with College Education reported less symptom burden (29.2 vs 36.8, range 10- 70; p<0.01) and better QOL (0.8 vs 0.7; p<0.01), an effect that remained significant in multivariable models. In a median follow up of 495 days (±135), the proportion of patients meeting all eligible QOC significantly increased in intervention group versus control group (increase of 38% versus 9%, p<0.01) (Fig. 1). Overall QOL started to improve among HealthPROMISE patients within 5 months and has consistently been above the control arm through a median interval of 495 days (Fig. 2). Table 1. Baseline characteristics of patients in the control and intervention arm Figure 1. Improvement in percentage of patients meeting eligible quality of care metrics in control (9%) versus Intervention (28%), p<0.01. Figure 2. Interim analysis showing improvement in symptom burden among intervention cohort (p<0.001). Conclusions: This is one of the first randomized controlled trials of app-based home monitoring in IBD patients. Fatigue and tension are the top two drivers of poor QOL among IBD patients. We found a significant improvement in QOC and QOL in intervention group. With a move towards value based care, digital medicine technology can play an effective role in tracking and managing patient population in IBD centers. Remote monitoring coordinators can help support proactive care without disrupting physicians' workflow.

Background: New evidence suggests that the GI tract of newborns starts to become colonised in utero.The source of these microbiota is of continued interest as the initial colonisation of bacteria is believed to play a crucial role in the development of the immune system.Yet, no data exist on the effect of IBD on gut microbiota of pregnant women and the bacteria they pass to their newborns.Methods: The MECONIUM Study is a prospective study aimed to investigate the role of IBD on pregnancy and baby's microbiome.Clinical data, stool, and saliva samples were collected from women with and without IBD during pregnancy.After delivery, serial stool samples were collected from the infants.The gut microbiota composition was evaluated using the 16s rRNA gene V3-V4 region.Results: In this pilot, 10 pregnant women (5 with IBD) and their 10 infants provided a total of 67 samples (mother 14 stool and 14 saliva, and infant 9 meconium and 30 stool samples collected at days 7, 14, 30, 60, and 90).All IBD cases were in remission throughout pregnancy.No mother was being treated with antibiotics or probiotics at the time of stool collection.Mean gestational age was 39.2 weeks.Five infants were born via C-section (3 from IBD mothers),

Background:Inflammatory Bowel Disease (IBD) is a chronic condition of the bowel that affects over 1.5 million people in the United States. The recurring nature of disease makes IBD patients' ideal candidates for patient-engaged care that is centered on enhanced self-management and improved doctor-patient communication. Thus the HealthPROMISE App was developed which is a unique cloud based PRO (patient reported outcomes) and decision support tool that empowers both patients and providers with a more comprehensive and continuous assessment. The App is implemented at 5 academic centers and undergoing pragmatic clinical trial at Mount Sinai Medical Center. Methods:Participants are being recruited after informed consent is obtained during face-face visits and are then randomized to either an interventional (i.e., HealthPROMISE) or control (i.e., education app) group. Patients in the HealthPROMISE arm are able to update their information and receive disease summary, quality metrics and a graph showing the trend of quality of life (SIBDQ) scores and resource utilization over time. Data is being collected in real time using the HealthPROMISE app from IBD patients at Mount Sinai and compared with paper-based surveys from patients at University of Pittsburgh Medical Center. SIBDQ scores are being generated and analyzed to look into psychosocial domains. Results:Of the 200 patients enrolled in the study at Mount Sinai Medical Centers, 102 were randomised to the intervention group and 98 to the control group (Females, 49.5%; White, 82.0%; Black, 11%; Hispanics, 9.5%; English as primary language, 96%; Everyday Computer Usage, 93%). When we analyzed the baseline data from both academic centers, we found striking similarity between prospectively collected data at UPMC on paper (n = 1543) with electronic data collected in real time from HealthPROMISE app in the last 5 months (N = 200). Both show fatigue and tension (anxiety) as major drivers of poor quality of life in more than 75% of patients with IBD. Overall, Psychosocial domains (Tension, Fatigue, Pain and Angry) were top 4 domains driving poor quality of life. Gastroenterology specific domains such as Bathroom issues and Weight maintenance were overall in good or fair control in majority of patients (>64%). In addition to comparative data between the 2 institutions, we will be presenting longitudinal data on overall quality of life and psychosocial domains among interventional patients in ongoing clinical trial. Conclusions:IBD patients need continuous assessment of psychosocial distress as they are the major contributing factors to poor quality of life. Interventions focused on improving stress and fatigue will be required to improve patients' well being and quality of life.

We read with interest the article by Ullman et al.1Ullman T Croog V Harpaz N Sachar D Itzkowitz S Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.Gastroenterology. 2003; 125: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar concerning the progression of flat low-grade dysplasia to advanced neoplasia in patients with long-standing ulcerative colitis.1Ullman T Croog V Harpaz N Sachar D Itzkowitz S Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.Gastroenterology. 2003; 125: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar The authors found that 7 of 46 patients with ulcerative colitis (UC) having at surveillance colonoscopy low-grade dysplasia in flat mucosa (LGDf) developed a colorectal cancer (CRC). They concluded that a finding of LGDf patients with long-standing UC should be followed by early colectomy. The results of Ullman et al.1Ullman T Croog V Harpaz N Sachar D Itzkowitz S Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.Gastroenterology. 2003; 125: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar are at variance with recent reports in the literature. Lim et al.2Lim C Dixon M Vail A Forman D Lynch A Axon A Ten year follow up of ulcerative colitis with and without low grade dysplasia.Gut. 2003; 52: 1127-1132Crossref PubMed Scopus (209) Google Scholar followed-up 30 patients with intact colon having long-standing UC and at least one histological diagnosis of LGD in flat mucosa. After 10 years, high-grade dysplasia (HGD) or CRC developed in 3 of 29 UCLGDf (10%) and in 4 of 97 UC controls (4.0%). That study did not show a statistically significant difference between the 2 groups. It should be pointed out that in the study by Lim et al. work sections were re-coded and sent to 5 well-known specialists in gastrointestinal pathology in the U.K. for histological evaluation. A consensus diagnosis-that is, at least 3 of 5 pathologists agreeing-was reached in only 38% of the cases. They concluded that agreement in LGD diagnosis between pathologists was uniformly poor, and therefore not sufficiently reliable to justify prophylactic colectomy. In a previous work,2Lim C Dixon M Vail A Forman D Lynch A Axon A Ten year follow up of ulcerative colitis with and without low grade dysplasia.Gut. 2003; 52: 1127-1132Crossref PubMed Scopus (209) Google Scholar we studied 60 patients with LGD in flat mucosa in at least one follow-up colonoscopy. Mean follow-up time from the initial colonoscopy with LGDf was 10 ± 6 (range, 1–22) years, with a mean time from onset of disease to discovery of LGDf of 17 ± 11 years (range, 1–55 years). LGDf was present in more than one biopsy in 37 (62%) of 60 patients at index colonoscopy. LGDf was again detected in 1.8 (1–6) subsequent colonoscopies in 73% (n = 44) of the 60 UC patients. Although LGDf occurred at several colonic levels and at repeated colonoscopies in 73% of the patients, no progression to HGD was found during the 10 years (mean) of surveillance, except in 2 cases developing DALM at follow-up. None of our patients showed HGD in flat mucosa. Thirteen patients were subjected to colectomy (7 for dysplasia, 6 for therapy failure): dysplasia was confirmed in 5 of these patients. We concluded that colectomy in cases with single or repeated LGD in flat mucosa does not appear to be justified.2Lim C Dixon M Vail A Forman D Lynch A Axon A Ten year follow up of ulcerative colitis with and without low grade dysplasia.Gut. 2003; 52: 1127-1132Crossref PubMed Scopus (209) Google Scholar In that work,3Befrits R Ljung T Jaramillo E Rubio C.A Low-grade dysplasia in extensive, long-standing inflammatory bowel disease a follow-up study.Dis Colon Rectum. 2002; 45: 615-620Crossref PubMed Scopus (160) Google Scholar and in similarity to Ullman et al.1Ullman T Croog V Harpaz N Sachar D Itzkowitz S Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.Gastroenterology. 2003; 125: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar report, only one pathologist reviewed all the slides with LGDf, and biopsy specimens were not subjected to a retrospective, blinded re-analysis. So why have those studies reached such contradictory results, namely that LGDf in UC should be followed by early colectomy,1Ullman T Croog V Harpaz N Sachar D Itzkowitz S Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.Gastroenterology. 2003; 125: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar vs. that colectomy in UC having single or repeated LGDf does not appear to be justified?3Befrits R Ljung T Jaramillo E Rubio C.A Low-grade dysplasia in extensive, long-standing inflammatory bowel disease a follow-up study.Dis Colon Rectum. 2002; 45: 615-620Crossref PubMed Scopus (160) Google Scholar Despite that all gastrointestinal pathologists use the criteria of the IBD Morphologic Study Group in diagnosing LGD, LGD in UC appears to be a collecting group of epithelial derangements with different biologic properties, as deduced from DNA studies of LGD4Befrits R Hammarberg C Rubio C.A Jaramillo E Tribukait B DNA aneuploidy and histologic dysplasia in long-standing ulcerative colitis. A 10-year follow-up study.Dis Colon Rectum. 1994; 37: 313-319Crossref PubMed Scopus (68) Google Scholar in patients with long-standing UC. But if that is the case, why is the more aggressive “side” of LGDf more frequent in American1Ullman T Croog V Harpaz N Sachar D Itzkowitz S Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis.Gastroenterology. 2003; 125: 1311-1319Abstract Full Text Full Text PDF PubMed Scopus (341) Google Scholar than in European2Lim C Dixon M Vail A Forman D Lynch A Axon A Ten year follow up of ulcerative colitis with and without low grade dysplasia.Gut. 2003; 52: 1127-1132Crossref PubMed Scopus (209) Google Scholar, 3Befrits R Ljung T Jaramillo E Rubio C.A Low-grade dysplasia in extensive, long-standing inflammatory bowel disease a follow-up study.Dis Colon Rectum. 2002; 45: 615-620Crossref PubMed Scopus (160) Google Scholar patients? Are there true transatlantic differences in the virulence of LGDf or is it just an histopathological controversy?