Stool Frequency Score Research Articles

METHODS TO DERIVE A MODIFIED MAYO SCORE FROM ELECTRONIC HEALTH RECORDS DATA

Abstract BACKGROUND The modified Mayo Score (MMS), which consists of stool frequency, rectal bleeding, and endoscopic subscores, is the most commonly used method for measuring disease activity in Ulcerative Colitis (UC) patients. It is a standard outcome measure in clinical trials, and is recommended as a clinical trial endpoint by the US Food and Drug Administration. Each component has a score from 0-3; the total MMS ranges from 0 to 9. MMS is infrequently recorded in routine care, in part because it requires an endoscopic assessment. Real world data, including electronic health record (EHR) databases, are useful for studying longitudinal disease and treatment outcomes, but most EHR databases do not include Mayo scores. Building off the methods described by Rudrapatna et al., 2021, we calculated a derived MMS using data elements available in EHRs. METHODS Data were derived from the OM1 PremiOM UC Dataset (OM1, Boston, MA), a multisource real-world database with linked healthcare claims and EHR data on US patients with UC (2013-present). Each of the three subscores was extracted from clinical notes and endoscopy reports, either by automated natural language processing methods or by abstraction by a trained medical abstractor. Rectal bleeding and stool frequency scores occurring within 4 months before or up to 1 month after the endoscopic score were combined to calculate a MMS. Multiple MMSs could be calculated for each patient, but each component score could contribute to only one MMS. RESULTS Among 12,849 UC patients, only 38 had a full Mayo score recorded in their notes, and 1 had a modified Mayo recorded. After applying the above algorithm, we were able to calculate a derived MMS for 739 patients. 220 patients had > 1 score available. Figure 1 shows the distribution of derived MMSs. Patients with a MMS were younger and more likely to be Asian, more likely to be treated with biologic therapies and less likely to be treated with mesalamine compared with those who could not have a MMS calculated (Table 1). CONCLUSIONS A derived MMS can be calculated from data that may be recorded in the medical record. Further work to validate these measures against a gold standard should be considered, but was not feasible in the OM1 dataset due to the paucity of observed Mayo scores in EHR data. Increased emphasis on standardized collection of relevant information in EHR systems would further improve the availability of derived MMSs. The population for which a MMS can be derived may have more severe disease and more frequent interactions with the healthcare system as evidenced by higher proportion of patients prescribed biologic therapies. MMSs can be derived and used to describe UC patients and could potentially be used to study longitudinal changes in patient disease status and treatment effectiveness in settings where observed scores are not available.

Reconstructive techniques following low anterior resection for carcinoma of the rectum: meta-analysis.

Multiple trials have compared reconstruction techniques used following the resection of distal rectal cancers, including straight colorectal anastomosis (SCA), colonic J pouch (CJP), side-to-end anastomosis (SEA), and transverse coloplasty (TCP). The latest meta-analysis on the subject concluded that all the reservoir techniques produce equally good surgical and functional outcomes compared with SCA. Numerous trials have been published in this regard subsequently. Hence, a network analysis (NMA) was performed to rank these techniques. A literature search of MEDLINE, Embase, and the Cochrane Library from their inception until April 2021 was conducted to identify randomized trials. Functional and surgical outcome data were pooled. ORs and standardized mean differences (MDs) were used as pooled effect size measures. A frequentist NMA model was used. Thirty-two trials met the eligibility criteria comprising 3072 patients. CJP showed better functional outcomes, such as low stool frequency and better incontinence score, both in the short term (stool frequency, MD -2.06, P < 0.001; incontinence, MD -1.17, P = 0.007) and intermediate term (stool frequency, MD -0.81, P = 0.021; incontinence MD -0.56, P = 0.083). Patients with an SEA (long-term OR 4.37; P = 0.030) or TCP (long-term OR 5.79; P < 0.001) used more antidiarrheal medications constantly. The urgency and sensation of incomplete evacuation favoured CJP in the short term. TCP was associated with a higher risk of anastomotic leakage (OR 12.85; P < 0.001) and stricture (OR 3.21; P = 0.012). Because of its better functional outcomes, CJP should be the reconstruction technique of choice. TCP showed increased anastomotic leak and stricture rates, warranting judicious use.

Milan Ultrasound Criteria Predict Relapse of Ulcerative Colitis in Remission

Introduction: Bowel ultrasound is a noninvasive alternative to endoscopy for assessing the disease activity of ulcerative colitis; however, it is unclear whether bowel ultrasound can predict subsequent relapse from remission. Materials and Methods: A retrospective cohort study enrolled patients with ulcerative colitis who underwent bowel ultrasound between July 2018 and July 2021 during clinical remission (patient-reported outcome-2 ≤1 and no rectal bleeding) for at least 3 months and were followed up for 1 year. Ultrasonographic findings (bowel wall thickness, bowel wall flow, bowel wall stratification, and enlarged lymph nodes), Milan ultrasound criteria, Mayo endoscopic subscore, C-reactive protein, and fecal calprotectin levels and their association with subsequent clinical relapse were assessed. Relapse was defined as rectal bleeding score ≥1, stool frequency score ≥2, or treatment intensification for symptoms. Results: 31% of the patients (18/58) relapsed within 1 year. No single ultrasonographic finding predicted relapse, whereas Milan ultrasound criteria >6.2 (p = 0.019), Mayo endoscopic subscore ≥1 (p = 0.013), and fecal calprotectin ≥250 μg/g (p = 0.040) were associated with a shorter time to relapse in the log-rank test. Milan ultrasound criteria >6.2 (hazard ratio 3.22; 95% confidence interval 1.14–9.08, p = 0.027) and Mayo endoscopic subscore ≥1 (hazard ratio 8.70; 95% confidence interval 1.11–68.1, p = 0.039) showed a higher risk of relapse according to a Cox proportional hazards model. Conclusion: Bowel ultrasound can predict subsequent clinical relapse from remission in patients with ulcerative colitis using the Milan ultrasound criteria.

Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial

Etrolizumab as induction and maintenance therapy in patients with moderately to severely active Crohn's disease (BERGAMOT): a randomised, placebo-controlled, double-blind, phase 3 trial

Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study.

Clinical studies of using probiotics for managing ulcerative colitis (UC) in Jordan are rare. Therefore, we aimed to evaluate the effect of probiotic supplementation on the clinical disease activity and biochemical parameters in patients with mild-to-moderately active UC. thirty mild-to-moderate ulcerative colitis patients were included and randomly assigned to participate in a double-blinded randomized study to receive the treatment (3×1010 of probiotic capsules [containing nine Lactobacillus and five Bifidobacterium species], or a placebo), and included in the intention-to-treat analysis. Only 24 completed the study and were included in the per-protocol analysis. Both groups were compared in terms of clinical disease activity and biochemical parameters at the beginning and the end of the study. Registered under ClinicalTrials.gov Identifier no. NCT04223479. There was a significant induction of remission in the probiotic group presented by improvement in the partial mayo score (PMS). Probiotic group had significantly lower stool frequency (0.00±0.00 vs. 1.17±1.19), global assessment (0.42±0.51 vs. 1.00±0.74, p=0.035), and total PMS score (1.33±0.49 vs. 3.42±1.78). In terms of mean and percent of change in post-to pre-treatment values, there was a significant reduction in C-reactive protein, and an increase in hemoglobin, hematocrit, and RBC levels in the probiotic group (p<0.05). Additionally, there was a significant reduction in the IgA level and an increase in IL-10 levels among the probiotic group compared to the placebo group (p=0.039). The use of probiotic therapy had significantly induced remission in UC patients, this was evidenced by the improvement in the Partial Mayo score. Furthermore, probiotic therapy had an appropriate effect on changes in hemoglobin, hematocrit, C-reactive protein, IgA, and IL-10 levels. This study was registered at ClinicalTrials.gov with the number NCT04223479.

S876 Efficacy of Deucravacitinib, an Oral, Selective, TYK2 Inhibitor, in Patients With Moderately to Severely Active Ulcerative Colitis and Prior Exposure to Biologic Therapy: Subanalysis From the Phase 2 LATTICE-UC Study

Introduction: Deucravacitinib (DEUC) is an oral, selective, allosteric inhibitor of tyrosine kinase 2 (TYK2), which mediates signaling of key cytokines in UC pathogenesis. In a phase 2 trial of DEUC in moderate to severe active UC, the primary endpoint was not met; however, a treatment effect was observed in patients with prior exposure to ≥1 biologic agent. Methods: LATTICE-UC (NCT03934216), a double-blind phase 2 trial, randomized patients with moderate to severe active UC (modified Mayo score [MMS] 5-9 with endoscopic score [MES] ≥2, rectal bleeding score [RBS] ≥1, stool frequency score [SFS] ≥2) 2:1 to DEUC 6 mg or placebo (PBO) twice daily (BID). This post-hoc analysis in biologic-exposed patients assessed clinical remission (MMS ≤2, with SFS ≤1, RBS=0, MES ≤1); clinical response (decrease from baseline [BL] in MMS ≥2 points and ≥30% with decrease in RBS ≥1 point or absolute RBS ≤1); endoscopic improvement (MES ≤1); and change from BL (CFB) in symptomatic Mayo score (RBS + SFS). Colonic tissue transcriptomes were assessed via bulk RNA sequencing in a subset of biologic-exposed patients (DEUC n=17; PBO n=9). Differential expression with limma-voom and pathway enrichment analysis via Gene Set Enrichment Analysis were performed. Results: Of 131 patients randomized, 48 (36.6%) were biologic-exposed (DEUC, 32/88 [36.4%]; PBO, 16/43 [37.2%]). At week 12, higher response rates were seen in patients receiving DEUC vs PBO in clinical remission (16.1% vs 0.0%), clinical response (29.0% vs 12.5%), and endoscopic improvement (25.8% vs 12.5%). Greater mean CFB in symptomatic Mayo score was observed at week 12 with DEUC (-2.1) vs PBO (-0.1) (Table). Type I interferon (IFN)‒regulated genes (IRG) were significantly reduced in colonic tissues at week 12 compared to BL in DEUC (FDR < 0.1) but not in PBO. Pathway enrichment analysis confirmed that the IFN pathway was down-regulated with DEUC treatment. In patients receiving DEUC who achieved clinical response at week 12, IRG expression was reduced compared with nonresponders; similar trends were seen in clinical remitters and in endoscopic improvers. Conclusion: Biologic-exposed patients treated with DEUC had greater improvements in clinical outcomes compared to PBO and had greater decreases in colonic IRG. The biomarker decreases were associated with clinical response or remission, suggesting inhibition of TYK2 pathways may be beneficial for UC. These results provide evidence the target was engaged and suggest a higher dose may have greater efficacy. Table 1. - Clinical Endpoints at Week 12 in Bio-Exposed Patients Endpoint Deucravacitinib6 mg BID (n = 31) Placebo (n = 16) Clinical remission response rate, mean 16.1% 0.0% Clinical response rate, mean 29.0% 12.5% Endoscopic improvement response rate, mean 25.8% 12.5% Symptomatic Mayo score, mean change from baseline (a) -2.1% -0.1 Table: (a) n for deucravacitinib and placebo is 16 and 9, respectively. BID, twice daily.

S761 Association Between Absolute Lymphocyte Count and Ozanimod Efficacy/Safety in Patients With Moderate/Severe Ulcerative Colitis: Results From the Phase 3 True North Study

Introduction: Ozanimod (OZA) is approved in the USA and EU for treatment (tx) of moderate/severe UC. OZA binding internalizes S1P1 receptors, reducing egress of lymphocyte subsets into circulation. OZA was approved in this patient (pt) population based on results of the phase 3 True North (TN) study (NCT02435992). Methods: We evaluated association between absolute lymphocyte count (ALC) and OZA efficacy/safety during TN’s induction period (IP) and maintenance period (MP). Pts were randomized to double-blind (DB) OZA 0.92 mg or placebo (PBO) or open-label (OL) OZA during 10-week (W) IP. Pts with clinical response to OZA at W10 were rerandomized to DB OZA or PBO for MP through W52. Rectal bleeding (RB), stool frequency (SF), composite Mayo, Physician’s Global Assessment (PGA), and endoscopy scores were assessed at baseline and as clinical outcomes at W10 and W52. Efficacy endpoints (EPs; clinical remission, clinical response, endoscopic improvement, mucosal healing, and histologic remission) were assessed at W10 and W52. Tx-emergent adverse events (TEAEs) and ALC were evaluated at baseline and W5, W10, W18, W28, W40, and W52. Results: During IP, 645 pts received DB OZA (n=429) or PBO (n=216) and 367 received OL OZA; for MP, 230 and 227 OZA-treated pts were rerandomized to OZA and PBO, respectively. Baseline ALC was not significantly correlated with clinical outcome at W10 or W52 as measured by changes from baseline RB, SF, Mayo, PGA, and endoscopy scores in pts on OZA or PBO. Baseline ALC was not predictive or prognostic for W10 and W52 responses based on the efficacy EPs. Reductions from baseline in mean ALC occurred by W5 with OZA and were significantly greater with OZA (53-54%) vs PBO (2.3%; P< .001). ALC plateaued by W10 and was maintained through W52 in pts on continuous OZA. ALC returned to PBO levels by W52 in pts who switched to PBO during MP. Change in ALC at W10 was generally not significantly correlated with changes in clinical outcomes at W10 or W52. Change in ALC at W5 was not predictive of W10 response; change in ALC at W10 was not predictive of W52 response. Reductions from baseline in ALC at all weeks were similar in OZA-treated pts with/without ≥1 TEAE and with/without infection TEAEs. Conclusion: ALC reductions occurring with OZA were reversed upon tx discontinuation and were not associated with TEAEs. Baseline ALC and ALC reductions were not predictive or prognostic for response. These findings support ALC as a pharmacodynamic biomarker but not as a prognostic or predictive biomarker.

Clinical study on sequential treatment of severe diarrhea irritable bowel syndrome with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.

ObjectiveTo study the effect of precision probiotic strains transplantation capsules on diarrhea irritable bowel syndrome compared with fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules.MethodsTwo patients with severe irritable bowel syndrome were treated with precision probiotic strains transplantation capsules, fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules in sequence. IBS-SSS, IBS-QoL, GSRS, stool frequency, stool character, degree of abdominal pain, GAD-7, and PHQ9 scores of patients at 0, 2, 4, 6, 8, 10, and 12 weeks of treatment were monitored and recorded, and stool samples were collected for metagenomics and metabolomics.ResultsIt was found that the IBS-SSS score of patient case 1 decreased by 175 points and that of patient case 2 decreased by 100 points after treatment of precision probiotic strains transplantation capsules. There was no significant decrease after fecal microbiota transplantation capsules and live combined bacillus subtilis and enterococcus faecium capsules were used. At the same time, compared with fecal microbiota transplantation and live combined bacillus subtilis and enterococcus faecium capsules, the IBS QoL, stool frequency, stool character, degree of abdominal pain and GAD-7 score of patient case 1 improved more significantly by the precision probiotic strains transplantation capsules. And the stool frequency and stool character score of patient case 2 decreased more significantly. Intestinal microbiota also improved more significantly after the precise capsule transplantation treatment. And we found Eubacterium_ Eligens showed the same change trend in the treatment of two patients, which may play a role in the treatment.Conclusionprecision probiotic strains transplantation capsules is more beneficial to improve the intestinal microbiota of patients than microbiota transplantation capsule and live combined bacillus subtilis and enterococcus faecium capsules, so as to better alleviate clinical symptoms. This study provides a more perfect and convenient therapeutic drugs for the treatment of IBS.

End of induction patient reported outcomes predict clinical remission and endoscopic improvement with vedolizumab and adalimumab in ulcerative colitis

Background Patient-reported outcomes (PROs) are increasingly emphasized as endpoints in clinical trials of ulcerative colitis (UC). However, the prognostic value of early improvement in PROs for long-term outcomes remains unclear. Methods This was a post-hoc analysis of 611 vedolizumab-treated or adalimumab-treated patients in the VARSITY trial (Clinicaltrial.gov: NCT02497469). Stool frequency (SF) and rectal bleeding score (RBS) as reported in the Mayo score at post-induction (week 6 and 14) was assessed for their association with one-year endoscopic improvement (EI), defined as Mayo endoscopic subscore <2; histo-endoscopic mucosal improvement (HEMI), defined as EI and Geboes highest grade <3.2, clinical remission (CR), defined as total Mayo score ≤2; and PRO-2 remission, defined as RBS of 0 and SF ≤1. Multivariable logistic regression models adjusted for confounders assessed the relationships between post-induction PROs and outcomes of interest at one-year. Results Patients with severe SF at week 6 were significantly less likely to achieve one-year EI compared to those with non-severe SF [aOR 0.40 (95% CI: 0.24–0.68), p < .001]. Absence of rectal bleeding at week 6 was associated with greater odds of achieving EI at one-year [aOR 2.21 (95% CI: 1.58–3.09), p < .001]. These findings were consistent across comparisons at week 14. Similar findings were observed for the outcomes of one-year HEMI, CR and PRO-2 remission. No difference was observed between the modified partial Mayo score and modified PRO-2 score. Conclusions Post-induction PROs strongly predict the odds of CR and EI in UC and simplified evaluations can be used to assess early response to UC therapies.

Upadacitinib: The New Jak Inhibitor in Town

Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicenter, double-blind, randomized trials. Lancet. 2022;399:2113–2128. Upadacitinib is an oral small molecule that has preferential inhibition of JAK1 that also inhibits JAK2, JAK3, and tyrosine kinase. Danese et al performed 3 phase III multicenter, double-blind, randomized trials assessing the efficacy and safety of upadacitinib as induction and maintenance therapy in patients with moderate to severe active ulcerative colitis. The 2 induction studies were UC1 and UC2, with each randomizing in a 2:1 ratio over 300 patients to upadacitinib 45 mg every other day, and over 150 patients to placebo. Patients who had a clinical response after 8 weeks of upadacitinib were eligible to enter UC3 (a maintenance study), where approximately 150 patients were each randomized to either upadacitinib 15 mg or 30 mg every other day or placebo for 52 weeks. The primary end points were clinical remission defined by an adapted Mayo score of ≤2, with a stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and an endoscopic subscore of ≤1 without friability. Secondary end points included improvements in endoscopic score, endoscopic remission, clinical response, histological improvement, bowel urgency, abdominal pain, inflammatory bowel disease questionnaire scores, mucosal healing and change in baseline in the Functional Assessment of Chronic Illness therapy score. Significantly more patients achieved clinical remission with upadacitinib 45 mg compared with placebo at 8 weeks (26% vs 5%, Δ 21% in UC1; 33% vs 4%, Δ 29% in UC2). In UC3, upadacitinib 15 mg and 30 mg was significantly superior to placebo in maintaining clinical remission at 52 weeks (42% and 52% vs 12%, Δ31% and Δ39%, respectively). All secondary end points were achieved in UC3 in the 15-mg and 30-mg groups compared with placebo. Upadacitinib showed similar safety and withdrawal profiles when compared with placebo. Events of cancer, adjudicated major adverse cardiac events, or venous thromboembolism were reported infrequently. There were no treatment-related deaths. The study limitations include the lack of data beyond 52 weeks. It also did not allow any dose optimization or de-escalation, and hence the benefits of these strategies remain unknown. Despite these limitations, upadacitinib demonstrated a positive efficacy and safety profile and could be an effective treatment option for patients with moderately to severely active ulcerative colitis. Excitingly, phase III trials have also reported positive signals for upadacitinib in achieving both induction and maintenance in patients with Crohn’s disease (Gastroenterology 2020;158:2123–2138) and hence real-world and long-term data will be paramount to help position this drug appropriately. This study highlights the potential of selective JAK inhibition and provides signals that optimizing JAK selectivity may culminate in more efficacious and safe drugs in inflammatory bowel disease.

Exocrine Pancreatic Insufficiency is Undiagnosed in Some Patients with Diarrhea-Predominant Irritable Bowel Syndrome Using the Rome IV Criteria.

Irritable bowel syndrome (IBS) is one of the most frequent disorders in clinical practice, with a mean 7.6-10.8% worldwide prevalence. A study showed that 6.1% of patients with diarrhea-predominant IBS (IBS-D) had severe exocrine pancreatic insufficiency (EPI). We aimed to identify the prevalence of EPI based on fecal elastase stool testing (Fel-1) in IBS-D and the clinical characteristics that may predict the diagnosis of EPI. Patients aged > 18years presenting to tertiary hospital outpatient clinics with IBS-D completed validated questionnaires and gave a stool sample where Fel-1 concentration was measured. Patients with Fel-1 < 100µg/g represented EPI and > 100 to < 200µg/g underwent testing for pancreatic pathology with laboratory and endoscopic ultrasound (EUS) evaluation. One hundred forty patients (mean age 60years, females 75.7%) were studied. EPI was found in 5% (95% CI 2.2-10.4), and pancreatic steatosis was the main EUS finding (71%). Dyspepsia was an independent factor associated with EPI (OR 34.7; 95% CI 4.95-366.37, p = 0.0007). After pancreatic enzyme replacement therapy (PERT), patients showed a significant improvement in the Bristol stool scale (p < 0.0001), bowel movements per day (p < 0.005), distension score (0.0009), pain score (0.0277) and IBS severity (0.0034). EPI is present in 5% of patients who fulfill Rome IV criteria for D-IBS, and dyspepsia was an independent symptom strongly associated with EPI. Pancreatic steatosis was the main endoscopic ultrasound finding. After PERT therapy, patients had significantly improved stool frequency, stool consistency, abdominal pain, distension and IBS severity score.

Risankizumab as maintenance therapy for moderately to severely active Crohn's disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial

There is a great unmet need for new therapeutics with novel mechanisms of action for patients with Crohn's disease. The ADVANCE and MOTIVATE studies showed that intravenous risankizumab, a selective p19 anti-interleukin (IL)-23 antibody, was efficacious and well tolerated as induction therapy. Here, we report the efficacy and safety of subcutaneous risankizumab as maintenance therapy. FORTIFY is a phase 3, multicentre, randomised, double-blind, placebo-controlled, maintenance withdrawal study across 273 clinical centres in 44 countries across North and South America, Europe, Oceania, Africa, and the Asia-Pacific region that enrolled participants with clinical response to risankizumab in the ADVANCE or MOTIVATE induction studies. Patients in ADVANCE or MOTIVATE were aged 16-80 years with moderately to severely active Crohn's disease. Patients in the FORTIFY substudy 1 were randomly assigned again (1:1:1) to receive either subcutaneous risankizumab 180 mg, subcutaneous risankizumab 360 mg, or withdrawal from risankizumab to receive subcutaneous placebo (herein referred to as withdrawal [subcutaneous placebo]). Treatment was given every 8 weeks. Patients were stratified by induction dose, post-induction endoscopic response, and clinical remission status. Patients, investigators, and study personnel were masked to treatment assignments. Week 52 co-primary endpoints were clinical remission (Crohn's disease activity index [CDAI] in the US protocol, or stool frequency and abdominal pain score in the non-US protocol) and endoscopic response in patients who received at least one dose of study drug during the 52-week maintenance period. Safety was assessed in patients receiving at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03105102. 712 patients were initially assessed and, between April 9, 2018, and April 24, 2020, 542 patients were randomly assigned to either the risankizumab 180 mg group (n=179), the risankizumab 360 mg group (n=179), or the placebo group (n=184). Greater clinical remission and endoscopic response rates were reached with 360 mg risankizumab versus placebo (CDAI clinical remission was reached in 74 (52%) of 141 patients vs 67 (41%) of 164 patients, adjusted difference 15% [95% CI 5-24]; stool frequency and abdominal pain score clinical remission was reached in 73 (52%) of 141 vs 65 (40%) of 164, adjusted difference 15% [5-25]; endoscopic response 66 (47%) of 141 patients vs 36 (22%) of 164 patients, adjusted difference 28% [19-37]). Higher rates of CDAI clinical remission and endoscopic response (but not stool frequency and abdominal pain score clinical remission [p=0·124]) were also reached with risankizumab 180 mg versus withdrawal (subcutaneous placebo; CDAI clinical remission reached in 87 [55%] of 157 patients, adjusted difference 15% [95% CI 5-24]; endoscopic response 74 [47%] of 157, adjusted difference 26% [17-35]). Results for more stringent endoscopic and composite endpoints and inflammatory biomarkers were consistent with a dose-response relationship. Maintenance treatment was well tolerated. Adverse event rates were similar among groups, and the most frequently reported adverse events in all treatment groups were worsening Crohn's disease, arthralgia, and headache. Subcutaneous risankizumab is a safe and efficacious treatment for maintenance of remission in patients with moderately to severely active Crohn's disease and offers a new therapeutic option for a broad range of patients by meeting endpoints that might change the future course of disease. AbbVie.

Risankizumab as induction therapy for Crohn's disease: results from the phase 3 ADVANCE and MOTIVATE induction trials

Risankizumab, an interleukin (IL)-23 p19 inhibitor, was evaluated for safety and efficacy as induction therapy in patients with moderately to severely active Crohn's disease. ADVANCE and MOTIVATE were randomised, double-masked, placebo-controlled, phase 3 induction studies. Eligible patients aged 16-80 years with moderately to severely active Crohn's disease, previously showing intolerance or inadequate response to one or more approved biologics or conventional therapy (ADVANCE) or to biologics (MOTIVATE), were randomly assigned to receive a single dose of intravenous risankizumab (600 mg or 1200 mg) or placebo (2:2:1 in ADVANCE, 1:1:1 in MOTIVATE) at weeks 0, 4, and 8. We used interactive response technology for random assignment, with stratification by number of previous failed biologics, corticosteroid use at baseline, and Simple Endoscopic Score for Crohn's disease (SES-CD). All patients and study personnel (excluding pharmacists who prepared intravenous solutions) were masked to treatment allocation throughout the study. Coprimary endpoints were clinical remission (defined by Crohn's disease activity index [CDAI] or patient-reported outcome criteria [average daily stool frequency and abdominal pain score]) and endoscopic response at week 12. The intention-to-treat population (all eligible patients who received at least one dose of study drug in the 12-week induction period) was analysed for efficacy outcomes. Safety was assessed in all patients who received at least one dose of study drug. Both trials were registered on ClinicalTrials.gov, NCT03105128 (ADVANCE) and NCT03104413 (MOTIVATE), and are now complete. Participants were enrolled between May 10, 2017, and Aug 24, 2020 (ADVANCE trial), and Dec 18, 2017 and Sept 9, 2020 (MOTIVATE trial). In ADVANCE, 931 patients were assigned to either risankizumab 600 mg (n=373), risankizumab 1200 mg (n=372), or placebo (n=186). In MOTIVATE, 618 patients were assigned to risankizumab 600 mg (n=206), risankizumab 1200 mg (n=205), or placebo (n=207). The primary analysis population comprised 850 participants in ADVANCE and 569 participants in MOTIVATE. All coprimary endpoints at week 12 were met in both trials with both doses of risankizumab (p values ≤0·0001). In ADVANCE, CDAI clinical remission rate was 45% (adjusted difference 21%, 95% CI 12-29; 152/336) with risankizumab 600 mg and 42% (17%, 8-25; 141/339) with risankizumab 1200 mg versus 25% (43/175) with placebo; stool frequency and abdominal pain score clinical remission rate was 43% (22%, 14-30; 146/336) with risankizumab 600 mg and 41% (19%, 11-27; 139/339) with risankizumab 1200 mg versus 22% (38/175) with placebo; and endoscopic response rate was 40% (28%, 21-35; 135/336) with risankizumab 600 mg and 32% (20%, 14-27; 109/339) with risankizumab 1200 mg versus 12% (21/175) with placebo. In MOTIVATE, CDAI clinical remission rate was 42% (22%, 13-31; 80/191) with risankizumab 600 mg and 40% (21%, 12-29; 77/191) with risankizumab 1200 mg versus 20% (37/187) with placebo; stool frequency and abdominal pain score clinical remission rate was 35% (15%, 6-24; 66/191) with risankizumab 600 mg and 40% (20%, 12-29; 76/191) with risankizumab 1200 mg versus 19% (36/187) with placebo; and endoscopic response rate was 29% (18%, 10-25; 55/191) with risankizumab 600 mg and 34% (23%, 15-31; 65/191) with risankizumab 1200 mg versus 11% (21/187) with placebo. The overall incidence of treatment-emergent adverse events was similar among the treatment groups in both trials. Three deaths occurred during induction (two in the placebo group [ADVANCE] and one in the risankizumab 1200 mg group [MOTIVATE]). The death in the risankizumab-treated patient was deemed unrelated to the study drug. Risankizumab was effective and well tolerated as induction therapy in patients with moderately to severely active Crohn's disease. AbbVie.

Factors associated with the prescription of probiotics in patients with inflammatory bowel disease: a cross-sectional study.

Commensal bacteria play an important role in the pathogenesis of inflammatory bowel disease (IBD) and probiotics have been used as treatment options. We aimed to explore the current use of probiotics and factors associated with their prescription in patients with IBD. This cross-sectional study was conducted on a single hospital-based cohort. Patients were eligible if they were ≥18 years old, visited the IBD clinic as an outpatient more than twice during the study period, and had a confirmed diagnosis of IBD. Patients were divided into two groups based on the prescription of probiotics. Clinical assessments were compared between the two groups. In total, 217 patients were enrolled in this study. In patients with Crohn disease (CD), moderate or severe abdominal pain; prior use of methotrexate (MTX), iron, thiopurines, or biologics; history of IBD-related surgery; and stool frequency were independently associated with the prescription of probiotics. In patients with ulcerative colitis (UC), moderate or severe abdominal pain, hematochezia, stool frequency, and moderate or severe physician global assessment score were independently associated with the prescription of probiotics. Increased disease activity may be associated with fewer prescriptions of probiotics in patients with IBD. However, physicians prescribed probiotics to control symptoms, such as abdominal pain and increased stool frequency in patients with UC and CD, and hematochezia in patients with UC. Additionally, the use of MTX and iron, and a history of IBD-related surgeries were associated with more frequent probiotic prescriptions in patients with CD.

Patient-reported continuous clinical response to golimumab in adults with moderately to severely active ulcerative colitis: results from GO OBSERVE, a real-world European observational study.

In PURSUIT, golimumab (GLM) was efficacious in patients with moderate-to-severe ulcerative colitis (UC). We assessed whether remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores is an effective real-world outcome measure for assessing maintenance of GLM-induced clinical response. This was a 54-week prospective, observational cohort study conducted at 43 European outpatient clinics in adults with moderate-to-severe UC who were biologic naïve or had received a maximum of one other biological therapy. Patients were treated according to European GLM UC label/local practice. Clinical response (based on partial or full Mayo score) was assessed at week 6, 10, or 14 of induction, depending on local practice. Investigators remotely monitored scores every 4 weeks. The primary endpoint was the proportion of induction responders in patient-reported continuous clinical response (pCCR) at week 54, defined as absence of UC flare based on combined patient-reported Mayo stool frequency and rectal bleeding scores every 4 weeks and full or partial Mayo score. A key secondary endpoint was the proportion of induction responders in clinical remission at week 54. Among 109 patients, 37 (34.0%) received at least two GLM induction doses and completed induction in clinical response (induction responders). At week 54, 15/37 (40.5%) induction responders were in pCCR, and 21/37 (56.8%) were in clinical remission. In daily clinical practice, regular remote monitoring of combined patient-reported Mayo stool frequency and rectal bleeding scores appears to be a meaningful real-world outcome measure for monitoring maintenance of GLM-induced clinical response in UC.

A Double-Blind, Randomized Intervention Study on the Effect of a Whey Protein Concentrate on E. coli-Induced Diarrhea in a Human Infection Model.

Infectious diseases are a major cause of morbidity and mortality worldwide. Nutritional interventions may enhance resistance to infectious diseases or help to reduce clinical symptoms. Here, we investigated whether a whey protein concentrate (WPC) could decrease diarrheagenic Escherichia coli-induced changes in reported stool frequency and gastrointestinal complaints in a double-blind, parallel 4-week intervention study. Subjects were randomly assigned to a whey hydrolysate placebo group, a low-dose WPC group or a high-dose WPC group. After 2 weeks of consumption, subjects (n = 121) were orally infected with a high dose of live but attenuated diarrheagenic E. coli (strain E1392/75-2A; 1E10 colony-forming units). Subjects recorded information on stool consistency and the frequency and severity of symptoms in an online diary. The primary outcome parameters were a change in stool frequency (stools per day) and a change in Gastrointestinal Symptom Rating Scale (GSRS) diarrhea score between the first and second days after infection. Neither dose of the whey protein concentrate in the dietary treatment affected the E. coli-induced increase in stool frequency or GSRS diarrhea score compared to placebo treatment. The composition of the microbiota shifted between the start of the study and after two weeks of consumption of the products, but no differences between the intervention groups were observed, possibly due to dietary guidelines that subjects had to adhere to during the study. In conclusion, consumption of the whey protein concentrate by healthy adults did not reduce diarrhea scores in an E. coli infection model compared to a whey hydrolysate placebo control.

P335 Utility of Intestinal Ultrasound in Monitoring Disease Activity in Ulcerative Colitis Patients Treated with Biologics

Abstract Background Given the invasive nature and high cost of frequent and repeated endoscopies needed to monitor UC, search for non-invasive diagnostic alternative is warranted. Intestinal ultrasound is a cost-effective, well-tolerated, non-invasive and readily available „point-of-care“ tool for the management of patients with Crohn’s disease. The role and widespread use of IUS for UC is still limited. We aimed to evaluate association between UC disease activity assessed by IUS on one hand and standard clinical, biochemical, and endoscopic parameters on the other one. Methods A single center, noninterventional retrospective chart review of adult UC patients treated with biologics at a tertiary center was performed. Routine clinical (stool frequency score – SFS, and rectal bleeding score – RBS), biochemical (FC), endoscopic (Mayo Endoscopic Subscore - MES), and IUS parameters (bowel wall thickness - BWT and colonic wall hyperemia assessed by colour Doppler imaging - CDS) were assessed before initiating biologics. Normal distribution was assessed using Shapiro-Wilk tests. Spearman correlation coefficients were calculated and ROC analysis was carried out. Results Total of, 44 patients (50% females, mean age, 37.4 ±, 14.05 years) with predominantly extensive UC (75%) were analysed. Positive correlation was observed between combination of BWT and level of CDS with SFS (rs = 0.68, p &amp;lt;, 0.01, N = 33) as well as with RBS (rs = 0.44, p &amp;lt;, 0.01, N = 34). Moreover FC values were in positive correlation with BWT (rs = 0.54, p &amp;lt;, 0.01, N = 36), levels of CDS (rs = 0.66, p &amp;lt;, 0.01, N = 33) and combination of BWT coupled with level of CDS (rs = 0.7, p &amp;lt;, 0.01, N = 33). In case of clinical active UC (SFS, 2/3 + RBS, 2/3 + FC &amp;gt;150 mg/g) correlation coefficient between FC level and BWT coupled with level of CDS rises to rs = 0.72, p &amp;lt;, 0.01, N = 30. Positive correlation of CDS with MES (rs = 0.65, p &amp;lt;, 0.01, N = 16) as well as between combination of BWT + level of CDS with MES (rs = 0.6, p &amp;lt;, 0.02, N = 16) was observed. Interestingly, positive correlation between BWT and MES didn′t reach statistical significance (rs = 0.42, p = 0.1, N = 16). The area under the curve (AUC) for the FC values and disease activity (defined as SFS, 2/3 + RBS, 2/3 + BWT &amp;gt;4 mm + presence of CDS) was, 0.96 (SE:, 0.03;, 95% CI, 0.89–0.99, p&amp;lt;0.01). FC values &amp;gt;134 mg/g were associated with active disease (sensitivity, 89.3%, specificity, 87.5%). Conclusion Results of this study show a good correlation between IUS and clinical, biochemical and endoscopic parameters of UC disease severity. IUS as a monitoring tool can be helpful in estimation of UC disease activity and can guide daily management of patients treated with biologics.

DOP43 Rapidity of ozanimod-induced symptomatic response and remission in patients with moderately to severely active Ulcerative Colitis: Results from the induction period of True North

Abstract Background Ozanimod, a sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in the US for the treatment of moderately to severely active ulcerative colitis (UC). In the pivotal phase 3 True North randomised controlled trial in moderate-to-severe UC, significantly more patients (pts) achieved clinical response and remission with ozanimod vs placebo (PBO) at week (wk) 10 of the induction period. Here, we report the rapidity of ozanimod-induced symptomatic response and remission in pts from True North (NCT02435992). Methods In True North, pts were randomised to once-daily ozanimod 0.92 mg (equivalent to ozanimod HCl 1 mg) or PBO (Cohort 1) or received open-label ozanimod (Cohort 2) during induction. This analysis evaluated symptomatic response (defined as ≥1 point and ≥30% decrease from baseline in adapted partial Mayo score and ≥1 point decrease from baseline in rectal bleeding score [RBS] or absolute RBS ≤1) and symptomatic remission (defined as RBS of 0 and stool frequency score [SFS] ≤1 point and ≥1 point decrease from baseline at each study visit from wk 2 through 10. Results During induction, 645 pts were randomised to ozanimod (n=429) or PBO (n=216) in Cohort 1, and 367 pts received open-label ozanimod in Cohort 2. Baseline demographics and clinical characteristics were well balanced across groups. Differences in symptomatic response were observed between ozanimod and PBO recipients in Cohort 1 as early as 2 wk after ozanimod initiation (1 wk post-titration) for the overall population (36.1% vs 26.4%; difference: 9.6% [95% CI, 2.1–17.0]; Figure 1) and tumour necrosis factor inhibitor (TNFi)-naïve pts (38.5%, n=301 vs 29.1%, n=151; difference: 9.4% [95% CI, 0.2–18.5]), and as early as 4 wk for TNFi-exposed pts (42.2%, n=128 vs 27.7%, n=65; difference: 15.8% [95% CI, 1.8–29.8]). Differences in symptomatic remission were observed between ozanimod and PBO recipients in Cohort 1 as early as 5 wk after ozanimod initiation (4 wk post-titration) for the overall population (26.3% vs 16.7%; difference: 8.6% [95% CI, 1.8–15.4] Figure 2), as early as 4 wk for TNFi-naïve pts (27.2% vs 17.9%; difference: 9.4% [95% CI, 1.5–17.4]), and as early as 8 wk for TNFi-exposed pts (22.7% vs 12.3%; difference: 11.7% [95% CI, 1.3–22.1]). Rates of symptomatic response and remission in pts receiving open-label ozanimod (Cohort 2) were similar to those in pts receiving randomised ozanimod (Cohort 1). Conclusion In the overall population, ozanimod was associated with higher rates of symptomatic response and remission vs PBO as early as 2 and 5 wk, respectively, after treatment initiation. Both clinical endpoints were more rapidly achieved in TNFi-naïve vs TNFi-exposed pts.

Clinical Efficacy of Probiotic Therapy on Bowel-Related Symptoms in Patients with Ulcerative Colitis during Endoscopic Remission: An Observational Study.

Background A substantial percentage of patients with ulcerative colitis (UC) have irritable bowel syndrome- (IBS-) like symptoms despite adequate treatment and endoscopic remission. In this study, we evaluated the clinical efficacy of probiotic therapy for residual IBS-like symptoms in patients with UC in endoscopic remission. Methods We conducted a multicenter, observational study between April 2018 and December 2020 across two university hospitals in Korea. Patients with UC whose IBS-like symptoms persisted during endoscopic remission were included in this study. Endoscopic remission was defined as a Mayo endoscopic score ≤ 1, and IBS-like symptoms were defined as those meeting the ROME-IV diagnostic criteria. A Biotop capsule® (Lactobacillus acidophilus, 75 mg; Clostridium butyricum TO-A, 25 mg; Bacillus mesentericus TO-A, 25 mg; and Streptococcus faecalis T-110, 5 mg) was administered three times daily for one month. All patients completed bowel-related symptom questionnaires and short inflammatory bowel disease questionnaires (SIBDQs) at the start and end of the 4-week treatment period. Results A total of 43 patients were enrolled and analyzed. Statistically significant improvements from baseline were observed at the end of the 4-week treatment. The total SIBDQ score improved from 50.6 to 53.6 (P = 0.005). SIBDQ scores of bowel function (P = 0.018), systemic function (P = 0.040), and social function (P = 0.005) improved. Stool frequency and Bristol stool scale scores improved after probiotic therapy (P < 0.05). Conclusion This study showed that probiotic administration improved bowel-related symptoms and quality of life in patients with UC whose IBS-like symptoms persisted during endoscopic remission. As this is an observational study and has no placebo-controlled arm, further prospective randomized controlled trials are needed to confirm these results.

P484 Remote monitoring allows an individualized approach and showed excellent usability at the infusion unit

Abstract Background Given the high impact on health-related quality of life (HRQoL), IBD patients may benefit from continued monitoring by specialized caregivers. Patient-reported outcomes (PRO) can be collected through telemedicine in a reliable way, allowing to monitor patients even in between hospital visits and supporting patient-physician interaction. The aim of this study was to implement an electronic questionnaire into routine clinical practice and to explore its added value. Methods Since May 2020, all IBD patients visiting the infusion unit of our tertiary referral centre (+/- 130 patients/week) receive an electronic questionnaire one week prior to their visit. Questions about disease activity are included through the two-component PRO (PRO2), and about HRQoL in form of the IBD Disk, which visually shows the impact of disease on ten different health domains over time (lower scores seen in quiescent disease). Based on PRO2 scores, clinical remission was defined as a liquid stool frequency ≤1 and an abdominal pain score ≤1 in patients with Crohn’s disease (CD), and as a stool frequency score ≤1 and no rectal bleeding in patients with ulcerative colitis (UC). We evaluated PROs and participation rate, and the System Usability Scale (SUS) was used to evaluate usability of the new system. Results In Jan-Feb 2021, a total of 447 unique IBD patients completed the full questionnaire at least once [48.0% participation rate, 62.9% CD, 53.0% male, median age (IQR) 46.5 (33.8–56.8) years, 94,9% on biologic therapy, 61.5% in clinical remission, Figure 1]. No association was found between sex, age (group) or IBD type and adherence to the questionnaire. Median (IQR) IBD Disk scores were significantly lower for remitters versus non-remitters [11 (3–25) vs. 40 (21–59), p&amp;lt;0.001]. The most affected health dimension in all patients regardless of remission state was energy with differences for remitters [median (IQR) 2 (0–5)] and non-remitters [median (IQR) 6 (3–8)]. Whereas all ten health dimensions of the IBD Disk were highly correlated with disease activity (p&amp;lt;0.001, Figure 2), no correlation was found with disease type, sex, age (group) or type of biologic therapy. In Feb 2021, 375 patients of the same cohort were randomly invited to complete the SUS. A median (IQR) SUS score of 85 (71.25–91.25) was found, indicating excellent usability of the new system (n=113). Conclusion The results show high correlation between disease activity and the impact on HRQoL, especially energy levels. Based on these PROs a more individualized approach at the infusion unit could be installed. This system is currently also implemented for IBD patients who do not visit the infusion unit but receive oral or subcutaneous therapy or no maintenance therapy.