Clinical Activity Index Research Articles

P562 Real world effectiveness and safety of ozanimod: One-year follow-up from a large tertiary center

Abstract Background Ozanimod is a first in class sphingosine-1-phosphate receptor modulator approved by the FDA for moderately-to-severely active ulcerative colitis (UC). Real world data describing use of ozanimod are limited. We provide one-year follow up results of our patient cohort treated with ozanimod. Methods This prospective, observational cohort study includes consecutive patients who initiated ozanimod at our center. We collected demographic, clinical, and laboratory data. Clinical disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI). Clinical response was defined as a decrease in ≥3 points in SCCAI from baseline with only patients with clinically active disease included in the analysis, and clinical remission was defined as an SCCAI score of ≤ 2. Results 47 patients have initiated ozanimod therapy at our center: 45 patients with ulcerative colitis (UC), 1 patient with Crohn’s colitis and 1 patient with lymphocytic colitis. Only patients with UC were included in the effectiveness analysis. Demographics are in Table 1: in the UC cohort, the mean age was 40.6 ±16.6 years, mean disease duration was 9.6 ±9.2 years, 26 (58%) were male, 23 (51%) had extensive colitis, and 34 (76%) had previous advanced therapy exposure. 19 had baseline endoscopy with a mean Mayo endoscopic score of 2.6 ±0.5. Clinical response, remission, and corticosteroid free remission (CSFR) rates at weeks 2, 4, 10, 24, and 52 are in Figure 1. At week 10, follow-up was available for 41 patients: 18 patients (55%) achieved clinical response, 24 (59%) clinical remission, and 22 (54%) achieved CSFR. At week 52, follow-up was available for 30 patients: 5 (17%) achieved clinical response, 5 (17%) clinical remission, and 4 (13%) achieved CSFR. There were no significant differences between advanced therapy naïve and experienced patients, including when stratified by the number of previous advanced therapies or prior use of vedolizumab (Figures 2A+B and 3). Patients with a > 75% reduction in absolute lymphocytes had numerically greater induction clinical response and remission rates (80% vs 54%, p=0.4 and 75% vs 53%, p=0.4, respectively). 13 patients experienced adverse events (AEs): hypertension (n=2), transient nausea (n=2), fatigue (n=3), dry skin (n=2), transient liver enzyme elevation (n=2) and transient headache (n=3). Two AEs required discontinuation – hypertensive crisis in a patient with a prior dx of hypertension, and fatigue. There were no episodes of symptomatic bradycardia. Conclusion We present one-year real world follow-up of ozanimod in a largely treatment-refractory cohort of patients with UC, and describe modest one-year effectiveness and a safety profile that is not different from that described in the clinical trials.

P560 Curcumin-QingDai combination for patients with active ulcerative colitis: A randomized double-blinded placebo-controlled trial

Abstract Background The herbal extracts Curcumin and QingDai (QD, Indigo) were previously shown to be effective in mild-moderate and in moderate-severe ulcerative colitis (UC), respectively. We evaluated the efficacy and safety of a combination of curcumin-QingDai (CurQD) in patients with active UC. Methods This was a two parts trial. Part 1 was an open label study of 4 weeks CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a modified Mayo endoscopic sub-score≥2. Part 2 was a placebo-controlled trial conducted in two centers in Israel and Greece, that randomized active UC patients at a 2:1 ratio to either enteric-coated CurQD 3gr/day or an identical placebo for eight weeks. The co-primary outcome at week 8 was clinical response (reduction in SCCAI of ≥3 points) and an objective evidence of response (Mayo endoscopic subscore improvement of ≥1 or 50% calprotectin reduction from baseline). Responding patients continued either curcumin or placebo alone for additional 8 weeks as maintenance treatment. Expression of Cyp1A1 in rectal mucosa was assessed as a measure of aryl-hydrocarbon receptor (AhR) pathway activation. Curcumin purity, and indigo and indirubin content in CurQD were confirmed by LC-MS/MS. Results There were 59 patients enrolled in the two study parts. In efficacy analysis of part 1, 7/10 responded including 3/10 who achieved clinical remission. For part 2, 95 patients were screened and 42 were included and randomized (48.8% biologics and/or immuno-modulators experienced, 36.6% biologics-experienced). The co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (p=0.033). Clinical response was observed in 85.7% versus 30.7% (p<0.001), 50% calprotectin-reduction in 46.4% versus 15.4% (p=0.08) and endoscopic improvement in 75% versus 20% (p=0.036), in the CurQD and placebo groups, respectively. The overall rate of adverse events was comparable between the groups. Among week-8 responders to CurQD, additional 8 weeks of treatment with curcumin alone resulted in 93%, 80% and 40% with maintained clinical response, clinical remission and clinical-biomarker response, respectively, at week 16. CurQD treatment uniquely resulted in activation of the AhR pathway, as gauged by a signficantly up-regulated expression of CYP1A1 in the rectal mucosa, which was not observed among patients receiving placebo, 5ASA or biologic drugs. Conclusion In this randomized controlled trial, combination CurQD was found to be effective for inducing remission in active UC patients. Induction of AhR may merit further study as a potential treatment target in active UC

P444 A systematic literature review (SLR) of real-world studies of advanced therapies in moderate-to-severe ulcerative colitis (UC): study, patient and clinical characteristics, and outcomes assessed

Abstract Background Variability in real-world (RW) study designs is often seen as a limitation for drawing conclusions. With more RW studies assessing effectiveness and safety of advanced therapies (ATs) in patients (pts) with moderate to severe UC, there is a need to better understand the study characteristics, clinical characteristics, treatments (Tx), and outcomes. Methods We conducted a SLR as per methodology described by Cochrane Collaboration and PRISMA guidelines, using Embase®, MEDLINE®, and MEDLINE®-In Process databases to find RW studies assessing biologics [bio] (adalimumab, golimumab, infliximab, vedolizumab/VEDO, and ustekinumab) or small molecules (filgotinib/FIL, ozanimod/OZA, and tofacitinib/TOFA) for adults with UC. Only products approved at the time of search were included. Studies published in English as full papers (Jan-2005–Feb-2022)or conference abstracts (Jan-2019–Feb-2022) were included. Studies with <30 pts or with only bio-naïve pts were excluded. Results From 3930 search results, 139 studies were included. Of these, 75% were published between 2019–2022; 64% were retrospective observational; and 53% were from 5 countries (Italy, US, Spain, UK, and Belgium). The median age of pts across studies was 26–55 years and male proportion ranged 25%–73% (Fig 1). 13% of studies had only bio-exposed pts, 63% had >50% pts bio-exposed and 28% presented sub-analysis for bio-exposed pts. Most studies (87%) were single arm; VEDO (41%) was the most evaluated Tx, followed by TOFA (20%). No studies were found for FIL or OZA. Clinical remission (CR; 69%), clinical response (69%), and steroid-free CR (46%) were commonly reported outcomes, whereas histologic (6%) and sustained remission (4%), and patient-reported outcomes (PROs; 5%) were uncommon (Fig 2). In studies reporting CR, Partial Mayo Score (PMS) or Full Mayo Score ≤2 alone or combined with rectal bleeding and stool frequency subscore ≤1 were commonly used definitions, followed by PMS ≤1 and Simple Colitis Clinical Activity Index ≤2. Most studies assessed outcomes within 52 weeks (76%). Any adverse event (AE; 46%), colectomy (46%), withdrawal due to AE (37%), and infections (24%) were frequently reported safety events. Only up to 12% of studies reported data on MACE, malignancies and VTE. Conclusion More than half of RW studies in moderate to severe UC originated from five countries with VEDO and TOFA being the most frequently assessed ATs. Comparative studies were limited. Several definitions of CR were used to describe effectiveness, and few studies assessed PROs and effectiveness beyond 1 year. Inconsistent reporting of safety events was identified. Future research should consider these findings when designing a study.

EFFICIENCY OF DUAL THERAPY WITH VEDOLIZUMAB AND TOFACITINIB IN REFRACTORY ULCERATIVE COLITIS PATIENTS – SINGLE CENTRE EXPERIENCE

Abstract INTRODUCTION Despite significant impact biological treatment had on prospects of patients with ulcerative colitis, there is still a substantial proportion of patients with either secondary loss of response or primary non-response to multiple drugs. Beside dose optimization and selection of drugs with different mechanism of action, combination of two different targeted molecules has been proposed in cases where inflammatory activity cannot get under control. This case series provide promising results of vedolizumab in combination with tofacitinib in treatment resistent UC patients. METHODS Patients with complicated refractory or acute severe colitis, in whom combined treatment with vedolizumab and tofacitinib based on shared clinical decision was started, were included. Data on demographics, treatment details, persistence and disease activity including laboratory markers, clinical activity index (partial Mayo score) during regular visits every 2 months up to one year after treatment initiation were collected. Currently available data were analyzed at 6 months of treatment. Endoscopic disease activity before and 2-6 months after dual therapy start was evaluated. RESULTS In total, 21 ulcerative colitis patients who were started on vedolizumab and tofacitinib dual therapy between October 2020 and September 2022 were included. Tofacitinib dose was 10mg bid in all patients and all patients on vedolizumab maintenance treatment had intensified dosing regimen. Mean patients age was 36.4±8.1 years, 47.6% were males and 52.4% females. Mean disease duration at baseline was 7.5±5.8 years. All patients had advanced disease including 61.9% with extensive colitis and 38.1% with left-sided colitis. At least 2 previous biologics in monotherapy were used in 85.7% of patients. Mean pMayo score at baseline was 5.6±1.9 and decreased to 0.5±0.9 at 6 months (p=0.0020). Initial fecal calprotectin in the cohort was 1829±2520µg/g vs. 225±257µg/g at 6 months (p=0.0068) and mean CRP changed from 11.4±17.1 to 5.4±7.2mg/l (p=ns). Endoscopic Mayo score before dual treatment initiation averaged 2.8±0.5 indicating mostly severe disease activity and decreased to 1.4±1.2 during follow-up endoscopy (p=0.0005) with half of the patients having only no to mild activity (eMayo 0-1). Up to now, dual therapy had to be terminated in 7 patients – 4 patients failed on the treatment, 1 refused to continue with dual therapy, 1 patient experienced adverse event (liver lesion) and 1 was discontinued for reimbursement reasons. CONCLUSION In the presented small cohort of patients, however, with refractory and complicated ulcerative colitis in whom other modalities were depleted or colectomy was considered, combined vedolizumab and tofacitinib treatment has proven to be very efficient with half of the patients reaching mucosal healing after 6 months and without raising significant safety concerns.

CURCUMIN-QINGDAI COMBINATION FOR PATIENTS WITH ACTIVE ULCERATIVE COLITIS: A RANDOMIZED DOUBLE-BLINDED PLACEBO-CONTROLLED CLINICAL TRIAL

Abstract BACKGROUND The herbal extracts Curcumin and QingDai were previously shown to be effective in mild-moderate and in moderate-severe ulcerative colitis (UC), respectively. We evaluated the efficacy and safety of a combination of curcumin-QingDai (CurQD) in patients with active UC. METHODS This was a two parts trial. Part 1 was an open label study of 4 weeks CurQD in patients with active UC, defined by a Simple Clinical Colitis Activity Index (SCCAI) score ≥5 and a modified Mayo endoscopic sub-score≥2. Part 2 was a placebo-controlled trial conducted in two centers in Israel and Greece, that randomized active UC patients at a 2:1 ratio to either enteric-coated CurQD 3gr/day or an identical placebo for eight weeks. The co-primary outcome at week 8 was clinical response (reduction in SCCAI of ≥3 points) and an objective evidence of response (Mayo endoscopic subscore improvement of ≥1 or 50% calprotectin reduction from baseline). Responding patients continued either Curcumin or placebo alone for additional 8 weeks as maintenance treatment. Expression of Cyp1A1 in rectal mucosa was assessed as a measure of aryl-hydrocarbon receptor (AhR) pathway activation. Curcumin purity, and indigo and indirubin content in CurQD were confirmed by LC-MS/MS. RESULTS 59 patients were enrolled in the two study parts. In efficacy analysis of part 1, 7/10 responded including 3/10 who achieved clinical remission. For part 2, 95 patients were screened and 42 were included and randomized. The co-primary outcome was achieved in 43% and 8% of CurQD and placebo patients, respectively (p=0.033). Clinical response was observed in 85.7% versus 30.7% (p<0.001), 50% calprotectin-reduction in 46.4% versus 15.4% (p=0.08) and endoscopic improvement in 75% versus 20% (p=0.036), in the CurQD and placebo groups, respectively. The overall rate of adverse events was comparable between the groups. Among week-8 responders to CurQD, additional 8 weeks of treatment with curcumin alone resulted in 93%, 80% and 40% with maintained clinical response, clinical remission and clinic-biomarker response, respectively, at week 16. CurQD treatment uniquely resulted in activation of the AhR pathway, as gauged by up-regulated expression of CYP1A1 in the rectal mucosa, which was not observed among patients receiving placebo, nor was it observed in patients responding to 5ASA or biologic drugs. CONCLUSION In this randomized controlled trial, combination CurQD was found to be effective for inducing remission in active UC patients. Induction of AhR may merit further study as a potential treatment target in active UC.

QINGDAI (QD) FOR PATIENTS WITH ACTIVE ULCERATIVE COLITIS: A RETROSPECTIVE ISRAELI NATIONAL EXPERIENCE

Abstract BACKGROUND QingDai (QD, Indigo) was shown to be effective for ulcerative colitis (UC) in randomized controlled trials and retrospective reports from Japan. However, experience with QD for UC in the West is extremely limited. We aimed to describe the effectiveness and safety of QD in a national cohort of patients with UC followed at tertiary referral centers in Israel. METHODS A retrospective study. We included adult patients who received QD for active UC (simple colitis clinical activity index (SCCAI)≥3) between 2018 -2022 at five academic centers. A majority of patients received QD in a combination with curcumin (CurQD). The primary outcome was clinical response at the end of induction (defined as the last follow-up visit between weeks 8 to 16 from the start of the treatment). Clinical response was defined as an improvement of SCCAI≥ 3 points; clinical remission as SCCAI≤2. C-reactive protein (CRP), fecal calprotectin (FC) levels and endoscopic Mayo score before and after treatment were compared when available. Starting corticosteroid or biologic treatment, hospitalization due to disease exacerbation, colectomy, discontinuation of treatment due to an adverse event or missing follow-up data were considered treatment failures RESULTS A total of 82 patients were included [median age-32, interquartile ratio (IQR)-23-41), 47 (57.3%) female; disease extent- 16 (20.5%)-proctitis, 28 (35.9%)- left-sided, 34 (43.6%) – pancolitis]. At treatment onset, 27 (41.5%) were treated with corticosteroids and 28 (34.1%) with a biologic or small molecule, 10 (12.9%) failed ≥ 3 biologics or small molecules. Median SCCAI was 6 (5-9), CRP- 5 (2-17) mg/L, fecal calprotectin levels – 698 (320 -1190) mg/g and endoscopic Mayo score- 2. QD was initiated in combination with curcumin (CurQD) in 77 (95.1%) of the patients. The last induction follow-up occurred after a median of 8 (8-12) weeks. At the end of induction, 64 (78%) responded to treatment, including 52 (63.4%) that achieved clinical remission (figure 1). At the end of induction, median SCCAI was 2 (1-3) (p<0.001), CRP- 2 (1-5) mg/L (p=0.003, 22 patients with paired measurements), FC levels -75 (12-139, 35 patients) mg/g (p<0.001, Figure 2) and median endoscopic Mayo score -1 (0-2) (p=0.03, 12 patients). Two (2.3%) patients experienced headaches and 5 (6.1%) mild liver function elevations that resolved spontaneously or following QD discontinuation (2 patients). CONCLUSIONS In this multicenter retrospective cohort study, QD treatment (predominantly as combination CurQD) was effective for induction of clinical response and remission in active UC patients, including biologic-experienced patients. All adverse events were mild and resolved either spontaneously or after QD discontinuation. Our results suggest QD as a potential effective and safe agent for induction of response and remission in patients with active UC.

PRELIMINARY EVIDENCE FOR A RELATIONSHIP BETWEEN HEART RATE VARIABILITY AND FATIGUE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE (IBD)

Abstract INTRODUCTION Heart Rate Variability (HRV), the variation in time between each heartbeat, is a proxy for vagus nerve function and validated indicator of cardiovascular health. Lower HRV is associated with increased risk of cardiac events and greater vulnerability to psychological stress. Fatigue is a common, frustrating and persistent symptom for IBD patients, with multifaceted mechanisms including nutrient deficiencies, inflammation, and poor sleep. Lower HRV is associated with higher fatigue in patients with cancer and myalgic encephalomyelitis. We postulate lower HRV could be associated with fatigue in IBD patients. METHODS Adults recruited from an outpatient IBD clinic wore a FitBit Inspire 2.0 for 14 days to monitor nighttime total time asleep, restlessness (# of ~30 second awakenings), and HRV (RMSSD in milliseconds (ms)). At baseline, weeks 1 and 2, participants completed the IBD Fatigue Scale and Harvey Bradshaw Index (HBI) or Simple Colitis Clinical Activity Index (SCCAI). Baseline laboratory testing for c-reactive protein (CRP), vitamins B12 and D, and ferritin was done. Averages for HRV and sleep metrics were computed for the 14-day period. Pearson’s correlations assessed relationships between all study variables (any p < .10). Then, partial correlations calculated the relationship between HRV and fatigue scores while controlling for identified confounding variables. We report an interim analysis. RESULTS 41 participants (63% female, 72.5% White, 92.7% non-Hispanic, 61% Crohn’s, 40.02 (SD=14.18) yrs old). Most (>75%) were in remission (HBI/SCCAI< 4). 34% had B12< 400 pg/mL, 20% vitamin D< 30 ng/mL, 54% ferritin< 50 ng/mL. Participants slept an average of 6.6 hours with 24.1(5.48) awakenings per night. All reported fatigue, with 43.9% having severe levels. Fatigue severity and impact remained consistent over the study (p=.106). Average HRV was 31.79(19.0) ms (Range: 11 - 92). Older patients had lower HRV (r= -0.34, p=.025) with no gender differences. Patients who reported more fatigue had higher CRP (r= 0.29), more active IBD symptoms (r= 0.62), and spent more time asleep (r= 0.20). When controlling for these variables and age, IBD patients with lower HRV reported significantly more global fatigue (r= -0.38, p=.041). The relationship between HRV and fatigue was larger for lower HRV and fatigue impact (r= -0.37, p=.047) than fatigue severity (r= -0.30, p=.11). No relationships existed for restlessness, vitamins B12 or D, or ferritin and fatigue. CONCLUSIONS When controlling for other contributors, patients with IBD and lower HRV reported more significant global fatigue and impact of fatigue on daily functioning. Findings may suggest lower HRV increases physical feelings of fatigue and reduces ability to manage fatigue impacts. Increasing HRV, e.g., with biofeedback training, may be a way to improve fatigue symptoms and management in IBD.

An endoscopic and histopathological assessment and correlation of endoscopic score with clinical activity index (CIBDAI) in the diagnosis of canine idiopathic inflammatory bowel disease.

Inflammatory bowel disease (IBD) in dogs is often characterized by a relapsing and remitting clinical course. Determination of inflammatory activity is important for assessing the disease extent, severity, and tailoring appropriate treatment. The study was conducted to record the macroscopic and microscopic changes associated with IBD to assess the usefulness of endoscopy in the diagnosis of the disease and to correlate the clinical activity index (CIBDAI) with endoscopic score. Thirty-three dogs with idiopathic IBD were selected after thorough examination and exclusion. Gastroduodenoscopy and colonoscopy were performed to document the gross macroscopic intestinal lesions. Histopathology of endoscopic aided biopsy samples was used to confirm the disease. Mucosal erythema and increased friability were the most predominant endoscopic findings in the stomach, duodenum, and colon of IBD dogs. Lymphoplasmacytic infiltration was predominant in the mucosal samples on histopathology and diffuse form of IBD is more common in canines. Gastroduodenoscopy and colonoscopy in combination with endoscopically guided biopsy and histopathology are of value in the assessment and diagnosis of IBD. There was no correlation between the clinical inflammatory bowel disease activity index (CIBDAI) with the endoscopic score. A diffuse form of IBD and colitis is more common in dogs in comparison to human IBD where the disease manifests in two distinct forms. Colonoscopy with ileal biopsy could act as a gold standard in the confirmation of diffuse IBD in dogs. CIBDAI can be used as a reliable measure of clinical signs of inflammation and histopathology can be used as a definitive diagnosis of intestinal inflammation.

Сравнительная оценка качества жизни и уровня тревоги и депрессии у пациентов с язвенным колитом

Aim: To assess the quality of life, the level of anxiety and depression in patients with ulcerative colitis (UC) depending on disease active/inactive status. Design: comparative prospective study. Materials and methods. In 2018–2020, a clinical study was conducted in Prof. S. V. Ochapovskiy Regional Clinical Hospital No. 1, which enrolled 218 patients: 178 patients with UC (139 patients with active disease and 39 patients with inactive disease) and 40 healthy volunteers (control group). In addition to routine examinations and faecal inflammatory markers, all patients underwent a quality-of-life assessment using The Short Form-36 (SF-36) and Inflammatory Bowel Disease Questionnaire (IBDQ), Clinical Activity Index (CAI), anxiety and depression evaluation using the Hospital Anxiety and Depression (HADS) scale. Results. The lowest mean values for SF-36 and the strongest correlations with CAI were observed in UC patients for the following domains: viability scale, overall health and emotional functioning (р < 0.05). Significant differences were recorded for IBDQ in mean values and correlations between the points on the scale and CAI for all domains (р = 0.0001). The strongest correlations were observed for the overall points and the “intestinal factor” domain (р = 0.0001). Lower mean values for SF-36 were in patients with chronic diseases not related to UC; for IBDQ, the situation was opposite — patients with extraintestinal UC signs had lower mean values. We found a correlation between HADS and CAI points which shows severity of an UC episode (r = 0.560; р = 0.01). Conclusions. The results demonstrate the importance of evaluation of the quality of life of patients with UC using both specific and nonspecific questionnaires, since they complement each other and allow personalising therapeutic approaches for patients with UC. Keywords: ulcerative colitis; inflammatory bowel diseases; quality of life; anxiety; depression.

Evaluation of intestinal ultrasound for disease activity assessment in patients with inflammatory bowel disease: A cross-sectional study at a tertiary centre in Malaysia.

The use of intestinal ultrasound (IUS) in the management of inflammatory bowel disease (IBD) is emerging. We aim to determine the performance of IUS in the assessment of disease activity in IBD. This is a prospective cross-sectional study of IUS performed on IBD patients in a tertiary centre. IUS parameters including intestinal wall thickness, loss of wall stratification, mesenteric fibrofatty proliferation, and increased vascularity were compared with endoscopic and clinical activity indices. Among the 51 patients, 58.8% were male, with a mean age of 41 years. Fifty-seven percent had underlying ulcerative colitis with mean disease duration of 8.4 years. Against ileocolonoscopy, IUS had a sensitivity of 67% (95% confidence interval (CI): 41-86) for detecting endoscopically active disease. It had high specificity of 97% (95% CI: 82-99) with positive and negative predictive values of 92% and 84%, respectively. Against clinical activity index, IUS had a sensitivity of 70% (95% CI: 35-92) and specificity of 85% (95% CI: 70-94) for detecting moderate to severe disease. Among individual IUS parameters, presence of bowel wall thickening (>3 mm) had the highest sensitivity (72%) for detecting endoscopically active disease. For per-bowel segment analysis, IUS (bowel wall thickening) was able to achieve 100% sensitivity and 95% specificity when examining the transverse colon. IUS has moderate sensitivity with excellent specificity in detecting active disease in IBD. IUS is most sensitive in detecting a disease at transverse colon. IUS can be employed as an adjunct in the assessment of IBD.

Positive zinc intake and a Japanese diet rich in n-3 fatty acids induces clinical remission in patients with mild active ulcerative colitis: a randomized interventional pilot study.

Zinc intake has reduced hospitalizations in patients with ulcerative colitis (UC), highlighting the need to maintain blood zinc levels. This prospective study investigated whether the promotion of zinc intake and a Japanese diet (high in n-3 fatty acids) could induce clinical remission in patients with mild active UC. Patients with mild active UC were randomly assigned to either (1) continue an unrestricted diet or (2) receive nutritional guidance promoting zinc intake and a Japanese diet. The primary endpoint was clinical remission at 24 weeks. Secondary endpoints were the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores, Clinical Activity Index (CAI), Geboes Histopathology Score (GHS), and biomarkers, including zinc levels, measured at 12 and 24 weeks. Nutritional assessments were performed using the Food Frequency Questionnaire. The CAI, UCEIS, and GHS scores were significantly lower in the intervention group than in the control group, with a significantly higher proportion of patients achieving clinical remission. Furthermore, the intervention group exhibited weight gain and significantly increased blood zinc levels. The combination of promoting dietary zinc intake and a Japanese diet rich in n-3 fatty acids can induce clinical remission in patients with mild active UC.

Combined effects of granulocyte and monocyte adsorption apheresis and corticosteroids on ulcerative colitis.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Change in Urgency Status Among Ulcerative Colitis Patients: Understanding a Potential Unmet Patient Need From the CorEvitas Inflammatory Bowel Disease Registry.

Fecal urgency is a common symptom of Ulcerative Colitis (UC). We explored the association between changes in fecal urgency for patient characteristics and evaluated the association between change in treatment and change in fecal urgency. The study cohort (n= 400) included UC patients in the CorEvitas Inflammatory Bowel Disease Registry between May 3, 2017 and September 1, 2020. Fecal urgency was defined using the Simple Clinical Colitis Activity Index. Urgency groups were formed by urgency at enrollment and 6-month follow-up visit: no persistent urgency at both visits (NPU); change from urgency to no urgency (UN); change from no urgency to urgency (NU); and persistent urgency at both visits (PU). Descriptive statistics were used to explore between urgency group differences at baseline and Kaplan-Meier curves to compare time to first treatment change. Groups included NPU (n= 175), UN (n= 86), NU (n= 56), and PU (n= 83). At enrollment, we found differences between groups for increased depression, anxiety, prior infections, diabetes; also, greater fatigue, pain, work impairment, work hours affected, and daily activities impacted. Compared to NPU patients, UN, NU, and PU patients were more likely to change treatment between enrollment and 6-month follow-up visit, and a higher proportion of UN, NU, and PU patients on a biologic at enrollment changed treatment vs the NPU group between both visits. Among real-world UC patients, fecal urgency status is associated with increased comorbidities and worse patient-reported outcomes and significant differences in change of treatment and time to treatment change. Urgency at any time point diminishes quality of life and may be a sign of inadequate therapy, which often is an indication to switch therapy.

Effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats

Background and aimThe etiopathogenesis of inflammatory bowel disease (IBD) is associated with different factors such as genetic, infectious, immunological, and environmental, including modification of the gut microbiota. IBD′s conventional pharmacological therapeutic approaches have become a challenge due to side effects, complications from prolonged use, and higher costs. Kefir fermented milk beverage is a functional food that has demonstrated multiple beneficial effects including anti-inflammatory and antioxidant activity. Alternative therapeutic strategies have been used for IBD as more natural products with low-cost and easy acquisition. The aim of this study is to evaluate the anti-inflammatory effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats. MethodsWe used 4 groups to perform this study: baseline control (BC), kefir control (KC), 5% untreated DSS-induced colitis (DSS), and 5% DSS-induced colitis treated with kefir (DSSK). The animals received fermented kefir milk beverage ad libitum for six days and the disease activity index was recorded daily. Colon samples were processed for Transmission Electron Microscopy and histopathological evaluation. We analyzed short fatty chain acids through the fecal sample using gas chromatography. ResultsKefir supplementation was able to reduce the clinical activity index and inflammatory process evidenced by decreased neutrophil accumulation, decreased reticulum edema, and increased autophagosomes. Also, showed a trend to increase the levels of acetate and propionate. ConclusionsOur results suggest that kefir fermented milk beverage may have an anti-inflammatory effect minimizing the intestinal damage of DSS-induced colitis.

Association Of Cellular Communication Network Factor 3 (CCN3) With Rheumatoid Arthritis Disease And It's Severity (Case-Control Study)

Background: An inflammatory condition that affects the joints in the limbs is rheumatoid arthritis. The most common symptom is chronic, recurrent joint inflammation. When patients are advanced, joint deformities and impairments may cause major impediments in the cardiac, skin, as well as other tissues and organs. A protein called cellular CCN3 is implicated in many biological processes such as cell adhesion, migration, as well as proliferation. Additionally, CCN3 has a role in a number of pathological processes, such as fibrosis, angiogenesis, and wound healing. CCN3 can be released from the cytoplasm. CCN3 may also be an inflammatory component in the course of RA. Future therapy approaches that focus on the activities and mechanisms of action of these proteins may result from better knowledge of how CCN proteins alter the pathophysiological processes underlying these types of arthritis and successfully reduce patients' pain (Wei et al., 2020). It was discovered that RA sera and tissues had increased levels of all CCN family members. IL6 production and CCN3 expression are correlated with disease activity (Giusti & Scotlandi, 2021).
 Methods: Between November 2021 and April 2022, a study including 70 patients with RA who met four or more 2010 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria for the condition and 70 healthy persons serving as control groups was conducted. All subjects had their disease activity score (DAS28-ESR), clinical activity index (CDAI), and rheumatoid factors (RF) detected by latex agglutination. By using an enzyme-linked immunosorbent assay, the levels of anti-cyclic citrullinated peptide (ACCP) and CCN3 in human serum samples were determined (ELISA).The age group of both the patients and the controls included in this study was 20-70. RA was found to be high in individuals of the age group >40 years, at a percentage of 71.4%. The mean age was 46.2±10.3 years for patients and 1.7±0.5 for controls.Results: The results clearly showed high serum CCN3 levels in patient groups with RA compared to control (P = 0.0001). CCN3 and ACCP have a significantly positive association at control (P = 0.0001). According to DAS28-ESR, there were significantly increased concentrations of CCN3 in severe patients at P values of 0.0001 in comparison to mild patients.
 Conclusions: The biomarker CCN3 is a good prognostic marker for the severity of RA.

S112 Optimal Timing and Donor-Patient Matching of Fecal Microbiota Transplantation for Ulcerative Colitis

Background: In recent years, rectifying imbalances of the gut microbiota with fecal microbiota transplantation (FMT) from healthy donors to patients suffering Ulcerative colitis (UC) have gained clinical interest. As several ongoing trials are exploring the possibility of using FMT to treat UC, discerning factors associated the long-term efficacy of FMT treatment becomes important. Our present study explored the factors related to the efficacy of FMT combined with triple-antibiotic therapy [amoxicillin, fosfomycin, and metronidazole (AFM); (A-FMT)] in patients with UC. Methods: Patients aged 16 years or older suffering from active UC with a Lichtiger’s clinical activity index (CAI) score ≥4 or Mayo endoscopic score (MES) ≥1 participated in the clinical study between March 2014 and October 2019. After rigorous screening, we selected relatives aged 20 years or older, or other volunteer donors. After 2 weeks of oral administration of 3 antibacterial agents, about 200ml of fresh or frozen stool solution of donor stool dissolved in saline solution was obtained by colonoscopy. CAI score at 4 weeks after treatment was defined as "response" if the CAI was ≤9 points and improved by ≥3 points, "remission" if the CAI further improved to ≤3 points, and "relapse" if the CAI increased or treatment was intensified at 48 weeks after treatment in the effective group. Results: Ninety-seven patients (68 males, 29 females, age 39.2 ± 12.9 years, disease duration 8.5 ± 8.0 years, CAI 10.7 ± 3.0, Mayo endoscopic subscore (MES) 1.8 ± 0.7) and 62 donors were included. 93 patients completed A-FMT, with an efficacy rate of 63.9% (ITT) at 4 weeks of treatment and a remission induction rate of 36.1%. The short-term efficacy was associated with pre-treatment Mayo endoscopic score (response P = 0.001, remission P < 0.001), history of corticosteroid treatment (response P = 0.04, remission P = 0.01), and history of tacrolimus treatment (response P = 0.04, remission P = 0.14). The cumulative non-relapse rate was significantly higher in the sibling donor group than in the parent-child donor group (P = 0.001). The age difference between patients and donors also affected the cumulative non-relapse rate (P = 0.01). Conclusion: In our study, the optimal timing for patients to receive A-FMT is before corticosteroid and tacrolimus treatments, and early-stage patients receive fecal transplants from siblings with the best clinical outcomes. While the short-term efficacy of A-FMT was related to the patient's own characteristics, the long-term efficacy was related to patient-donor matching.

Efficacy of a Digital Personalized Elimination Diet for the Self-Management of Irritable Bowel Syndrome and Comorbid Irritable Bowel Syndrome and Inflammatory Bowel Disease.

Most patients with irritable bowel syndrome (IBS) and dual-diagnosis IBS and inflammatory bowel disease (IBD) report that symptoms originate from or are exacerbated by trigger foods. Despite patient interest and need, there is no consensus on what diet is optimal. Popular diets have notable limitations including cost, length, implementation complexity, and lack of personalization. This pilot study evaluated the feasibility, desirability, and effect on gastrointestinal symptoms of a digitally delivered personalized elimination diet for patients with IBS and comorbid IBS/IBD, powered by machine learning. Participants were recruited online and were provided access to a digital personalized nutrition tool for 9 weeks (N = 37; IBS only = 16, Crohn's disease and IBS = 9, and ulcerative colitis and IBS = 12). Significant symptom improvement was seen for 81% of participants at study midpoint and persisted for 70% at end point, measured by the relevant symptom severity score (IBS symptom severity score, Patient Simple Clinical Colitis Activity Index, or Mobile Health Index for Crohn's disease). Clinically significant symptom improvement was observed in 78% of participants at midpoint and 62% at end point. Twenty-five participants (67.6%) achieved total symptomatic resolution by the end of study. Patient-reported quality of life improved for 89% of participants. Ninety-five percentage daily engagement, 95% retention, 89% adherence and 92% satisfaction with the program were reported. Dietary elimination can improve symptoms and quality of life in patients with IBS and comorbid IBS/IBD. Digital technology can personalize dietary interventions and improve adherence. Randomized controlled trials are warranted.

Effectiveness and safety of tofacitinib for ulcerative colitis: two-year results of the ICC Registry.

Tofacitinib is an oral Janus kinase (JAK) inhibitor and is registered for the treatment of ulcerative colitis (UC). The effectiveness of tofacitinib has been evaluated up to 12 months of treatment. The aim of this study was to assess the effectiveness and safety of 24 months of tofacitinib use in UC patients in the Netherlands. Patients initiating tofacitinib treatment were included in the ICC Registry, a nationwide, observational registry. Patients were prospectively evaluated for up to 24 months. The primary outcome was corticosteroid-free clinical remission (CSFR, Simple Clinical Colitis Activity Index [SCCAI] ≤2) at week 104. Secondary outcomes included biochemical remission (C-reactive protein (CRP) ≤5mg/L and faecal calprotectin (FC) ≤250 μg/g), safety, and discontinuation rate. We included 110 patients of whom 104 (94.5%) were anti-TNF experienced. After 104 weeks of tofacitinib, 31.8% (34/107) were in CSFR, 23.4% (25/107) in biochemical remission and 18.7% (20/107) in combined clinical and biochemical remission. Of the patients in CSFR at week 52, 76.5% (26/34) remained so after 104 weeks of treatment. Sixty-one patients (55.5%) discontinued tofacitinib after a median duration of 13 weeks (IQR 7-34). The main reasons for discontinuation were non-response (59%), loss of response (14.8%), and adverse events (18%). There were 33.9 possible tofacitinib-related adverse events per 100 patient-years during follow-up. Adverse events most probably related to tofacitinibwere skin reactions and headaches. There were 6.4 herpes zoster infections per 100 patient-years. Tofacitinib was effective in 31.8% of patients after 24 months of treatment.

Complete Blood Count-Derived Inflammatory Markers Changes in Dogs with Chronic Inflammatory Enteropathy Treated with Adipose-Derived Mesenchymal Stem Cells.

Simple SummaryMesenchymal stem cells exhibit anti-inflammatory properties, and their administration to dogs with chronic inflammatory enteropathy has been shown to be safe and effective. Neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and the systemic immuno-inflammation index are considered novel biomarkers to assess the inflammatory status of patients. The present study aimed to compare the clinical evolution and the changes in these inflammatory biomarkers in dogs with chronic enteropathy before and after cell therapy. The values of the three inflammatory biomarkers were higher in dogs with chronic enteropathy before the treatment compared to the values obtained from healthy dogs. After treatment, those values decreased significantly over time, and nine months later, no difference was observed between healthy dogs and dogs with chronic enteropathy in two of the three studied markers. A relationship between the amelioration of the clinical signs and the decrease in the blood inflammatory markers was also established. These results demonstrate that the clinical improvement of patients with chronic enteropathy treated with stem cells is accompanied by a normalization of the inflammatory biomarkers studied.Adipose-derived mesenchymal stem cells (Ad-MSCs) exhibit anti-inflammatory and immunomodulatory activities. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) have been reported as novel biomarkers of the inflammatory state; however, they have never been examined in dogs with chronic inflammatory enteropathy (CIE) treated with Ad-MSCs. This study aimed to compare the clinical evolution and the changes in the NLR, PLR, and SII in dogs with CIE before and after cell therapy. Sixteen dogs with CIE were administered a single intravenous dose of Ad-MSCs. The canine chronic enteropathy clinical activity index (CCECAI), NLR, PLR, and SII were assessed before treatment (T0) and at 2 (T2) and 9 (T9) months post-treatment and compared over time and with the reference values obtained from a group of healthy dogs. NLR, PLR, and SII were significantly increased at T0 compared to the reference values, decreasing significantly over time. At T9, the NLR and SII did not differ from the reference values, but PLR remained above the reference values. A correlation was observed between CCECAI and the three markers. These findings show that the clinical improvement of dogs with CIE treated with Ad-MSCs is accompanied by a normalization of the inflammatory status.

Inflammatory Biomarkers of Extracellular Matrix Remodeling and Disease Activity in Crohn's Disease and Ulcerative Colitis.

Extracellular matrix (ECM) homeostasis is highly affected in active inflammatory bowel disease (IBD). The aim of the study was to investigate serological biomarkers of type III, IV, and V collagen degradation and formation, and their association with disease activity in IBD. ECM remodeling serum biomarkers were measured in 162 IBD patients, 110 with Crohn’s disease (CD) and 52 with ulcerative colitis (UC), and in 29 healthy donors. Biomarkers of type III collagen degradation (C3M) and formation (PRO-C3), type IV collagen degradation (C4M) and formation (PRO-C4), and type V collagen formation (PRO-C5) were measured using ELISA. Inflammatory activity was assessed using endoscopic, clinical, and biochemical activity indices. The highest diagnostic value was identified in discriminating endoscopically moderate to severe disease in CD (PRO-C3, C3M/PRO-C3, and C4M with AUC of 0.70, 0.73, and 0.69, respectively) and UC (C3M, C3M/PRO-C3, and C4M with AUC of 0.86, 0.80, and 0.76, respectively). C4M and C3M/PRO-C3 in combination yielded AUC of 0.93 (0.66–0.90) in CD and 0.94 (0.65–0.99) in UC. This study confirmed that ECM remodeling reflected disease activity in CD and UC. A combination of C4M, C3M, and PRO-C3 biomarkers may potentially be considered as a biomarker differentiating moderate to severe endoscopic disease.