Rubin, David T.

Abstract Background Recommendations regarding signs and symptoms that should prompt referral of patients with inflammatory bowel disease (IBD) to an IBD specialist for a consultation could serve to improve the quality of care for these patients. Our aim was to develop a consult care pathway consisting of clinical features related to IBD that should prompt appropriate consultation. Methods A scoping literature review was performed to identify clinical features that should prompt consultation with an IBD specialist. A panel of 11 experts was convened over 4 meetings to develop a consult care pathway using the RAND/UCLA Appropriateness Method. Items identified via scoping review were ranked and were divided into major and minor criteria. Additionally, a literature and panel review was conducted assessing potential barriers and facilitators to implementing the consult care pathway. Results Of 43 features assessed, 13 were included in the care pathway as major criteria and 15 were included as minor criteria. Experts agreed that stratification into major criteria and minor criteria was appropriate and that 1 major or 2 or more minor criteria should be required to consider consultation. The greatest barrier to implementation was considered to be organizational resource allocation, while endorsements by national gastroenterology and general medicine societies were considered to be the strongest facilitator. Conclusions This novel referral care pathway identifies key criteria that could be used to triage patients with IBD who would benefit from IBD specialist consultation. Future research will be required to validate these findings and assess the impact of implementing this pathway in routine IBD-related care.

AbstractBackgroundThe safety of a third dose of SARS-CoV-2 mRNA vaccination in patients with inflammatory bowel disease is unknown.MethodsWe compared symptoms following a third SARS-CoV-2 mRNA vaccine dose with symptoms after the second dose in IBD.ResultsThe study group included 594 patients (70% female, 58% BNT162b2). Overall, 41% reported symptoms after a third dose. Symptom frequency and severity were lower after the third dose relative to the second dose for every organ system, except for gastrointestinal symptoms which were marginally worse.ConclusionThe frequency and severity of symptoms after a third mRNA vaccine dose are generally similar or milder than after a second dose for most organ systems.

Abstract Background Ozanimod was approved by the FDA to treat patients (pts) with moderately to severely active Ulcerative Colitis (UC) based on the results from the 52-week (wk) phase 3 True North (TN) study. We sought to evaluate long-term efficacy and safety of ozanimod. Methods We examined data from an interim analysis of pts in the TN parent study who entered the ongoing TN open-label extension (OLE). Pts entered the TN OLE from the phase 3 TN study if they were non-responders at the end of induction, lost response during maintenance, or completed maintenance treatment, or from the phase 2 Touchstone OLE if they remained at study closure and received once-daily oral ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg). Clinical remission, clinical response, endoscopic improvement, and corticosteroid (CS)-free remission were evaluated at Wks 46, 94, and 142 in the TN OLE for all pts who entered the OLE from the TN parent study, and in the subset of pts in clinical response at the OLE entry. The data were analysed in the intent-to-treat population using observed cases (OC), which used the number of pts remaining in the study at the corresponding time point, and non-responder imputation (NRI), which used the number of pts remaining in the study at the corresponding time point and those who withdrew before the time point but would have reached the time point if they had stayed. Treatment-emergent adverse events were evaluated from the pooled phase 2 and phase 3 UC studies. Results A total of 823 pts from TN entered the TN OLE; as of the cut-off date (Sept 30, 2020), 64% completed Wk 46, 34% completed Wk 94, and 14% completed Wk 142 of the OLE. The most common reason for discontinuation was lack of efficacy (21%). Baseline demographics were similar as in the TN study. A total of 261 pts were in clinical response at the time of OLE entry. OC analyses showed that the percentage of pts achieving clinical remission, clinical response, endoscopic improvement, and CS-free remission was maintained over time (Table). Efficacy in the responders was higher compared to the total population and was comparable within the endpoints at Wks 46 and 94. Using the more conservative NRI analysis, the proportion of pts achieving each endpoint was lower than in the OC; however, after 94 wks of OLE treatment, 34% of all pts and 55% of the responders still maintained clinical response. No new safety signals were seen with longer-term ozanimod use in the 1158 pts in the pooled population. Conclusion UC pts from the phase 3 TN study demonstrated maintenance of response with long-term ozanimod treatment. These data reflect approximately 2 years of additional ozanimod treatment, with no new safety signals identified.

Abstract Background The oral, selective Janus kinase inhibitor upadacitinib (UPA) has demonstrated efficacy as induction and maintenance therapy in patients with moderately to severely active Ulcerative Colitis (UC) in a Phase 3 clinical programme comprising two identical induction trials (U-ACHIEVE Induction [NCT02819635] and U-ACCOMPLISH [NCT03653026]) and a maintenance study (U-ACHIEVE Maintenance). This analysis assessed the impact of baseline corticosteroid (CS) use on the efficacy and safety of UPA in patients in these trials. Methods Patients were randomised 2:1 to UPA 45 mg once daily (QD) or placebo (PBO) for 8 weeks. Patients who achieved a clinical response at Week 8 were re-randomised 1:1:1 to UPA 15 mg QD, UPA 30 mg QD or PBO for 52 weeks. Here, we report induction and maintenance endpoints and safety data stratified by baseline CS use. Results Baseline demographics and disease characteristics were generally well balanced across treatment groups, regardless of baseline CS use. Clinical remission rates among patients receiving UPA 45 mg induction therapy did not differ by baseline CS use (Figure 1A). In the induction period, rates of treatment-emergent adverse events of special interest (AESI), including serious and opportunistic infections, were increased in the UPA 45 mg plus baseline CS group compared with the PBO and UPA without baseline CS groups (Table 1). In the maintenance study, CS tapering was mandated. CS-free remission at Week 52 (defined as clinical remission, per Adapted Mayo Score, and CS free for ≥90 days immediately prior to Week 52) was significantly increased with UPA 30 and 15 mg compared with PBO (both p<0.001; Figure 1B). Among patients receiving UPA maintenance, rates of treatment-emergent AESIs in the baseline CS versus no baseline CS groups were 33% versus 39% and 27% versus 35% in the UPA 30 mg and UPA 15 mg groups, respectively. Malignancy, major adverse cardiovascular events, venous thromboembolic events, and serious and opportunistic infections were reported infrequently in patients receiving UPA (Table 1). Conclusion This post hoc analysis suggests that, in patients with moderately to severely active UC, UPA is superior to PBO in conferring CS-free remission. Baseline CS use was not associated with any apparent efficacy benefit and carried a potential increased safety risk. These results suggest that achieving early disease control with UPA and without CS use is an optimal treatment strategy for this population.

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

INTRODUCTION: The purpose of this study was to find out whether dissemination of gastroenterology and hepatology (GI) research on social media networks correlates with citation count at 5 years. METHODS: We correlated the Altmetric Attention Score with Web of Science citation counts at 5 years for scholarly work published in the 10 highest impact factor GI journals in 2014. RESULTS: In 4,026 analyzed items, the correlation ( r ) between Altmetric Attention Score and citations at 5 years was 0.62 ( P < 0.001), representing strong correlation. Twitter was the platform with the strongest correlation with citations. DISCUSSION: Social media attention garnered by GI scholarly work strongly correlates with the number of citations at 5 years.

BACKGROUND: Cross-sectional studies in ulcerative colitis (UC) have shown at best a moderate association between histologic and clinical measures of disease activity, but few longitudinal studies have evaluated this relationship. As endoscopy and histology are both independent predictors of clinical outcomes in UC, there remains a need to assess these measures in parallel to demonstrate clinical benefit. HICKORY (NCT02100696) is an ongoing Phase 3 study evaluating etrolizumab in anti-tumor necrosis factor (aTNF)–experienced patients with moderate-to-severe UC. The correlation between histologic changes and established disease activity measures at end of induction (week 14) was assessed using data from the open-label induction (OLI) cohort of HICKORY. METHODS: Study analysis is based on data from patients in the OLI cohort who received ≥1 dose of etrolizumab 105 mg subcutaneously every 4 weeks during the 14-week induction phase. Baseline and week 14 biopsies were scored by 1 of 4 central readers using the Nancy histologic index (NHI) and the Robarts histopathology index (RHI) in patients who had active baseline histology (NHI >1 and RHI >3) and complete scoring at week 14 (n = 97). Binary week 14 histologic outcomes were characterized by presence or absence of neutrophils (NHI ≤1 or RHI ≤3 and Geboes subgrades 2B.0/3.0). Mayo Clinic score (MCS) endoscopic subscore (ES) was used to assess endoscopy. Pairwise associations were quantified by Spearman correlation (ρ; for correlation between change from baseline scores) and Cohen kappa coefficients (κ; for agreement among week 14 outcomes). ΔNHI and ΔRHI were compared to determine presence of a minimum clinically important difference (MCID) in MCS (∆MCS ≥3 from baseline). RESULTS: At week 14, 22% (21/97), 23% (22/97), and 8% (8/97) of patients achieved resolution of neutrophilic inflammation based on either NHI or RHI/Geboes, endoscopic improvement (ES ≤ 1), and endoscopic remission (ES = 0), respectively. Among patients with endoscopic improvement and endoscopic remission, neutrophilic resolution was achieved in 55% (12/22) and 75% (6/8) of patients, respectively. ΔNHI and ΔRHI were highly correlated (ρ = 0.91). There was weak to no association between ΔNHI/ΔRHI/ΔES and Δfecal calprotectin (ρ = –0.02 to 0.38), ΔC-reactive protein (ρ = 0.03 to 0.07), Δalbumin (ρ = –0.19 to –0.10), Δhemoglobin (ρ = –0.22 to –0.19), and Δsegmented neutrophils in the blood (ρ = –0.06 to 0.01). Weak correlations were observed between ΔNHI/ΔRHI and ΔES (ρ = 0.26–0.27), Δrectal bleeding (ρ = 0.24–0.28), and Δstool frequency (ρ = 0.40–0.42). Correlations between NHI, RHI/Geboes, and ES with symptomatic outcomes were weak (κ = 0.28–0.45). Difference in the mean grouped by achievement of ΔMCS ≥3 suggests MCIDs in ΔNHI and ΔRHI of 1.2 and 8.6, respectively. CONCLUSION(S): The analysis showed weak to moderate agreement between changes in histologic scores and changes in endoscopic scores, and weak to no agreement between changes in histologic scores and changes in laboratory results at week 14. There was a weak correlation between histologic scores and symptoms at the end of induction. MCID results suggest that both the NHI and RHI appear to effectively evaluate neutrophilic resolution, making the changes in score more clinically interpretable.