Harvey-Bradshaw Index Score Research Articles

P238 Symptom burden and indolent disease in newly diagnosed patients with ulcerative colitis and Crohn’s disease - a Copenhagen IBD Inception Cohort Study

Abstract Background The early course of ulcerative colitis (UC) and Crohn’s disease (CD) is difficult to predict, particularly regarding identifying patients for whom an indolent course might be expected. Therefore, we aimed to investigate the initial course of UC and CD and clinical predictors hereof in a generalizable population-based inception cohort. Methods We initiated a prospective population-based inception cohort of newly diagnosed patients with UC and CD between May 1st, 2021 and November 1st, 2021, according to the Copenhagen IBD Criteria within the geographical uptake area of Hvidovre University Hospital and Herlev University Hospital. All patients were examined systematically by IBD specialists at diagnosis using endoscopy, magnetic resonance (MR) enterography, and patient-reported measures including Simple Clinical Colitis Index (SCCAI) and Harvey-Bradshaw Index (HBI) for UC and CD, respectively. Indolent disease presentation was defined as the absence of UC or CD-related hospitalization, surgery, or decision to start steroid, immunomodulator, or biologic therapy within three months of follow-up. In addition, well-recognized predictors of long-term disease course of UC and CD were a priori defined and implemented in a univariate logistic model, and factors with a p-value smaller than 0.10 were included in the multivariate model. Results The study included 63 adult patients with UC and 50 with CD. At diagnosis, 23 (36.5%) and 13 (26.0%) patients with UC and CD were in clinical remission according to their SCCAI or HBI score, respectively (Table 1). The symptomatic disease burden is outlined in Table 2–3. Interestingly, well-recognized risk factors for the long-term disease course of UC and CD, including disease extent, behavior, baseline endoscopy, MR enterography, and serologic data, did not predict the initial disease course in a multivariable analysis (Table 4). However, C-reactive protein <10 mg/L were associated with an indolent course of UC (adjusted odds ratio=6.2 (95% confidence interval 1.3–38.9), p=0.03). Conclusion The preliminary data from the ongoing prospective population-based cohort study indicate that very heterogenous disease course patterns might be experienced very early. As initial disease control is considered critical for long-term outcomes, this study highlights the inapplicability of long-term predictors for the short-term disease course. It emphasizes the need for further development of simple clinical tools or biomarkers for early patient stratification.

P155 Incidence and significance of vitamin D deficiency at Inflammatory Bowel Disease inception in the COVID era

Abstract Background Vitamin D, a key regulator of immune response, is known to be lower in Inflammatory Bowel Disease (IBD) patients than the general population. Disparity in the incidence of deficiency between ethnic groups has previously been demonstrated. We measured vitamin D in a unique multi-ethnic inception cohort to correlate this with traditional IBD scores and patient reported outcome measures including the ‘IBD Disk’. Methods Data regarding demographics, ethnicity, faecal calprotectin (FCAL) and baseline blood results including Vitamin D was collected prospectively from January-October 2021, from adults presenting with suspected IBD. Montreal classification, Harvey-Bradshaw Index or Partial Mayo score, endoscopic disease severity indices and IBD Disk score were documented in those with confirmed diagnosis at endoscopy. Vitamin D deficiency was defined as <50nmol/l. Results 179 patients had a Vitamin D level recorded; 58 Ulcerative colitis (UC), 58 Crohn’s disease (CD), 53 non-IBD controls and 10 still awaiting diagnosis. 44(76%) CD, 32(55%) UC and 28(53%) non-IBD control patients were Vitamin D deficient at first presentation. Median levels were lowest in CD, with a significant difference between CD and non-IBD (median 35nmol/l; IQR 24.05 vs. median 48.9nmol/l; IQR 49.1; p=0.004). Regression analysis demonstrated patients with Crohn’s disease were four times more likely to have Vitamin D deficiency compared to UC (OR 4.08; 95% CI 1.35–12.36) at diagnosis. No correlation was seen between absolute vitamin D levels or vitamin deficiency state and faecal calprotectin when controlled for various factors regardless of the IBD subtype. The cohort distributions are demonstrated in Figure 1. Within the IBD cohort, Vitamin D levels were significantly lower in Black or Asian patients vs White patients (median 28.5; IQR 20.85 vs median 43.3; IQR 33.95; p=0.004). Figure 2 provides an overview of the cohort distributions. Vitamin D levels at presentation, as demonstrated in Table 1, did not correlate with Disease activity markers (DAMS) whereas baseline haemoglobin did, albeit weakly. Interestingly, Vitamin D and Haemoglobin correlated without reaching statistical significance (Spearman’s rho 0.149; p=0.08). Conclusion Our inception dataset demonstrates high rates of Vitamin D deficiency comparable to prior studies in IBD patients. Both CD and Black or Asian ethnicity were strongly associated with Vitamin D deficiency. Baseline Vitamin D did not correlate with disease activity markers whereas anaemia showed consistent weak association. Our study demonstrates the problem of hypovitaminosis D and the importance of measurement and supplementation, particularly in Black and Asian CD patients, from diagnosis.

P473 Real world experience with the Crohn’s Disease Exclusion Diet (CDED) in a tertiary IBD clinic

Abstract Background The Crohn’s Disease Exclusion Diet (CDED) is a whole-food diet designed to reduce exposure to dietary components, hypothesized to negatively affect the microbiome, intestinal barrier, and immune response. In a clinical study in adults with mild-moderate CD (<5 years duration), an inflammatory phenotype involving the terminal ileum, it induced clinical, biochemical and endoscopic disease remission. We aimed to describe our real-world experience with the CDED, in a clinically diverse CD population. Methods A retrospective cohort study of CD patients prescribed with the CDED, between 1.2018 and 11.21. Patients’ medical background, medical therapy, nutritional status and clinical disease activity as well as adherence and clinical outcomes were documented from patients’ medical files. Results The CDED was recommended to 218 CD patients. Of these, 62 were excluded from the analysis due to lack of medical information (n=11), prior personal experience with the CDED (n=23), patient’s refusal (n=24), and stoma patients (n=4). The CDED was initiated in 155 patients (age 37.7±16.3, 66% men, disease duration 7.8±9.6), 35.3% had colonic/ileo-colonic disease, 23.7% and 25% had a stricturing and penetrating disease respectively, 27.5% had a history of intestinal resection, 19.9% had extra-intestinal involvement, and 7.7% had a severe endoscopic disease at diet initiation. Indications for therapy included patient’s will (44.7%), adjunctive therapy (23.7%), bridge with biologic induction (20.4%), rescue therapy (3.9%), exhaustion/contraindication of other advanced therapy options (1.4%), de-escalation of biologics (0.7%), preparation for surgery (0.7%), and others (3.9%). Upon initiation, 67.3% (n=105) had an active disease [Harvey Bradshaw index (HBI) ≥5 / Calprotectin ≥250 g/l] and 32.7% were in remission. Physician and dietician follow-up at the end of phase 1 was documented in 89 (57.4%) and 74 (47.7%) of patients with an active disease (mean follow-up period 14.6±9.3 weeks). Fifty-eight percent of patients with dietary follow-up (n=43) were fairly-fully compliant to the CDED. Clinical response (drop in HBI>2 points) and remission (HBI<5) at the end of phase 1, were achieved by 58.9% (n=62) and 57.5% (n=60) of patients who were treated for an active disease (n=105). Clinical remission rate at the end of phase 1 was lower among patients with higher baseline HBI score (P for trend=0.028), lower dietary adherence (P for trend<0.001) and a surgical history (P=0.033). Conclusion The CDED may have efficacy across different clinical scenarios. Adherence is reasonable, and is associated with higher remission rates among patients treated for an active disease.

Urine and Serum Metabolomic Profiles Differ by Disease Activity in Pregnant Women With Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD), inclusive of ulcerative colitis and Crohn's disease, are chronic inflammatory conditions that impact women of childbearing age. It has been previously shown that IBD is associated with altered metabolomic profiles, but whether metabolomic changes also affect pregnant patients with IBD is completely unknown. This was a prospective cohort study comprised of 48 pregnant women with IBD who were followed throughout preconception and pregnancy. IBD disease activity was measured using biochemical markers C-reactive protein or fecal calprotectin using enzyme-linked immunosorbent assay and clinical disease activity using Harvey-Bradshaw Index or partial Mayo scores. Serum and urine samples were collected from preconception, trimester 1, and trimester 2 and analyzed using nuclear magnetic resonance spectroscopy combined with metabolomics set enrichment analysis. We identified a total of 24 urine metabolites and 17 serum metabolites which were altered by active disease across pregnancy. First trimester (T1) active disease-associated metabolites were enriched in "amino acid metabolism" and "fatty-acid β-oxidation." The leading urine metabolites at T1 were trimethyl-N-oxide (TMAO), succinic acid, and 3-hydroxy-2-methylbutyric acid, and leading serum metabolites were TMAO, glucose, and acetic acid. Multivariate modeling using serum TMAO, glucose, and acetic acid predicts T1 disease activity and correlated with mode of delivery and infant weights at delivery. Moreover, cross-time point modeling using metabolomes predicted future disease flare-up during pregnancy. These results suggest select host metabolites may be able to discriminate and predict disease activity and are correlated with pregnancy outcomes at delivery. This warrants further validation of metabolomics to monitor IBD in pregnancy.

Leucine-Rich Alpha-2 Glycoprotein in Monitoring Disease Activity and Intestinal Stenosis in Inflammatory Bowel Disease.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 μg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.

Poor Patient-Reported Outcomes and Impaired Work Productivity in Patients With Inflammatory Bowel Disease in Remission.

This study aimed to evaluate associations between disease severity, patient-reported outcomes (PROs), and work productivity in patients with inflammatory bowel disease (IBD [Crohn's disease (CD) and ulcerative colitis (UC)]). Patients diagnosed with CD or UC enrolled in CorEvitas' IBD Registry (May 2017 to September 2019) were included (N= 1543; CD, n= 812; UC, n= 731). Disease severity was assessed using the Harvey-Bradshaw Index (CD) and partial Mayo Score (UC); psychosocial PROs (Patient-Reported Outcomes Measurement Information System [PROMIS]) and work productivity (Work Productivity and Activity Impairment [WPAI]) were assessed. Univariable and multivariable regression analyses assessed associations between PROs and disease severity. Among CD patients, 67.4% were in remission, 19.2% had mild disease, and 13.4% had moderate/severe disease; among UC patients, 52.7% were in remission, 35.3% had mild disease, and 12.0% had moderate/severe disease. For CD patients in remission, unadjusted percentages of patients with PROMIS scores outside normal limits ranged from 18.9% (depression) to 34.9% (fatigue). For CD patients in remission, 54.3% reported work productivity loss, and 57.1% reported activity impairment. The unadjusted percentage of UC patients in remission with scores outside normal limits ranged from 15.7% (depression) to 28.7% (fatigue) for PROMIS and 10.5% (absenteeism) to 43.5% (activity impairment) for WPAI. Impairment increased with IBD severity. Congruently, adjusted estimates showed significant impairment in PROMIS and WPAI scores for CD and UC patients in remission. In this real-world analysis, IBD patients across the spectrum of activity, from remission to severe disease, experienced impaired psychosocial function and reduced work productivity. Impairment, even among patients in remission, indicates an unmet need in this patient population.

Effectiveness of ustekinumab in patients with refractory Crohn's disease: a multicentre real-life study in Italy.

Background:The effectiveness of ustekinumab in patients with refractory Crohn’s disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD.Methods:All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey–Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values.Results:Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08–0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events).Conclusion:Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial

The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18-55 years with mild-to-moderate Crohn's disease (defined by a Harvey-Bradshaw Index score of 5-14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey-Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov, NCT02231814. Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. Azrieli Foundation and Nestle Health Science.

S911 Sexual Dysfunction Improves With Biologic Therapy in Men and Women With IBD

Introduction: Patients with inflammatory bowel disease (IBD) have a high degree of sexual dysfunction (SD). Few studies have tracked SD longitudinally or with IBD-specific scales. We aimed to correlate SD with clinical and psychosocial IBD indices and track SD longitudinally using the IBD- Female and Male Sexual Dysfunction Scales (IBD-FSDS and MSDS). Methods: We surveyed patients with Crohn’s disease (CD) and ulcerative colitis (UC) starting a new biologic or small molecule therapy (anti-TNF, anti-integrin, anti-IL12/23, JAK inhibitor) at start of induction and 2- and 6-months. Surveys also included the PROMIS Brief Sexual Function and Satisfaction Profile, disease activity indices [Harvey-Bradshaw index (HBI), partial Mayo score], and psychosocial scales [Patient Health Questionnaire-9 (PHQ-9), Short IBD Questionnaire (SIBDQ), and IBD-Disability Index (IBDDI)]. Clinical data included endoscopic scores, inflammatory biomarkers (ESR, CRP, calprotectin), and IBD history. Therapy response was defined as a reduction in HBI, pMayo, SCCAI ≥3 or total HBI ≤ 4, pMayo < 2, SCCAI ≤2 at survey 3. Results: 123 patients (68 males and 53 females) completed survey 1, 89 completed survey 2, and 74 completed survey 3. The median age was 31 years. 58% had CD, 42% had UC, and 31% were non-white. At induction, the median MSDS score was 6 out of 40 (IQR 2.5-13.5) and FSDS was 12 out of 60 (3-27.5); (Table 1Table 1.: Median Sexual Dysfunction, Clinical Disease Activity and Psychosocial Scores Stratified by Therapeutic Response.). SD scores strongly correlated with PROMIS scores (r=-0.75, p< 0.001), Mayo endoscopic score (r=0.71, p< 0.001), and moderately correlated with HBI (r=0.49, p=0.002) and pMayo scores (0.44, p=0.03), but not with inflammatory biomarkers. SD also correlated with SIBDQ (r=0.55, p< 0.001), PHQ-9 (r=0.42, p< 0.001), and IBD-DI (r=0.47, p< 0.001). MSDS scores significantly improved from survey 1 to survey 3 (p= 0.039). FSDS scores numerically improved but did not reach significance. Over 50% of patients had a significant response to therapy. When stratified by treatment response, MSDS and FSDS scores improved significantly among therapy responders (p=0.006 and p= 0.041, respectively) as did Male-PROMIS scores. This improvement was not observed in non-responders (p=0.27). HBI, SCCAI, pMayo, SIBDQ and IBD-DI also improved among responders. Conclusion: In this longitudinal cohort, there was a strong correlation between SD, disease activity, and psychosocial indices. Among therapy responders, there was a significant improvement in SD. These findings further clarify the relationship between SD and therapeutic response in IBD.

Switch z originálního na bio­similární adalimumab SB-5 u nemocných s Crohnovou chorobou – dlouhodobé výsledky

Background and aims: Originator-adalimumab, an established treatment for patients with Crohn‘s disease (CD) showed no difference in efficacy or adverse events vs the adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks of treatment. To understand the long-term efficacy of SB5-adalimumab in CD, patients who switched from originator-adalimumab to SB5-adalimumab were compared to a cohort who remained on originator-adalimumab over a follow up of 104 weeks. Methods: In this analysis, data on patients ≥18 years and diagnosed with CD treated at the IBD ISCARE centre were collected prospectively between July 2018 and January 2021. Clinical disease activity as measured by Harvey-Bradshaw index (HBI) at Week 52 was the primary outcome, while C-reactive protein (CRP), faecal calprotectin (FC), adalimumab trough levels in Weeks 10, 26, 52, 78, and 104, adverse events leading to therapy withdrawal, and persistence on treatment were secondary outcomes. To ensure comparable treatment cohorts, patients were propensity score matched (PSM) for age, gender, diagnosis, and disease activity. Results: A total of 54 patients were matched according to the given criteria in each group. At Week 52, the mean [SD] HBI score was 3.2 (2.5) in the originator-adalimumab group and 4.0 (3.6) in SB5-adalimumab patients (difference [95% CI] –0.78 [–2.8, 1.3]). Similarly, no clinically significant differences in CRP, FC, or trough levels were noted between originator-adalimumab and SB5-adalimumab cohorts through Week 52. The Kaplan-Meier estimates (95% CI) of patients remaining on treatment for the originator-adalimumab vs SB5-adalimumab cohorts were 0.870 (0.785–0.965) vs 0.648 (0.533–0.789) at Week 52. Conclusions: These long-term study results in CD patients after a non-medical switch from originator-adalimumab to SB5-adalimumab showed that the biosimilar SB5 had similar therapeutic effects as originator-adalimumab in terms of clinical disease activity, biological parameters, and pharmacokinetics profile at the primary endpoint of 52 weeks, as well as 104 weeks. Differences in persistence were not clinically driven. Persistence on treatment was lower in patients treated with biosimilar adalimumab SB-5.

P527 Investigating fatigue in vedolizumab-treated patients with ulcerative colitis or Crohn’s disease from a Belgian registry

Abstract Background Vedolizumab (VDZ) has demonstrated remission in ulcerative colitis (UC) and Crohn’s disease (CD), but its impact on patient (pt) fatigue is not well understood. Herein we report interim fatigue analysis data from a Belgian registry of VDZ-treated pts. Methods Ad-hoc analysis from the prospective observational Belgian VDZ registry (started, November 2016; data cutoff, February 2019), a sub-study of the European VDZ post-authorization safety study (ENcePP EUPAS6469) included pts aged ≥18 years with UC or CD with ongoing VDZ intravenous therapy (≥2 weeks) at recruitment. At baseline (recruitment) and every 6 months, physicians collected data (follow-up was 3 years or 1 year after last dose if VDZ was discontinued [whichever occurred first] and pts completed the 13-Item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Clinical remission was defined as Harvey-Bradshaw Index (HBI) score &amp;lt;5 for CD, and partial Mayo score (pMS) &amp;lt;2 with no individual subscore &amp;gt;1 for UC. This analysis explored the association (using generalized estimating equations) between all available FACIT-F total scores and baseline demographic, clinical, and treatment characteristics in the treatment analysis set (TAS; pts had ≥1 VDZ dose and ≥1 year of follow-up records). Results The registry enrolled 202 VDZ-treated UC and CD pts from 19 Belgian centres. TAS included 141 pts (UC 47, CD 94); median follow-up was 537 days; 140/141 pts had ≥1 FACIT-F score. In the UC and CD groups, respectively, 68% and 42% of pts were male; median (IQR) age at index date was 51 (37–59) and 40 (29–52); and baseline median (IQR) FACIT-F total score was 39 (32–46) and 32 (24–40). Lower FACIT-F score (more fatigue) was associated with higher pMS in UC (p&amp;lt;0.001), and higher HBI score (p=0.01) and having ongoing fistulas at baseline (p=0.01) in CD (Table). Less fatigue was associated with being in remission at baseline in both UC and CD (p&amp;lt;0.01). Being male was associated with less fatigue in the overall population and CD (p&amp;lt;0.01), but not in UC alone. Baseline occurrence of extra intestinal manifestations (EIMs) was associated with more fatigue in the overall group (p=0.037); however few pts (UC 4; CD 8) had EIMs. UC pts had less fatigue than CD pts (p=0.004). From baseline to month 24, the change in median (IQR) FACIT-F total score was -3.0 (-12.0 to 5.0) points for UC and 3.5 (-1.0 to 18.0) for CD. Conclusion These real-world data from a long-term registry study of VDZ-treated pts in Belgium demonstrate that higher pMS and HBI score, active fistulae, and EIM occurrence at baseline may be associated with more fatigue in IBD pts. Pts treated with VDZ had no significant change in FACIT-F total score over 24 months.

P289 A French nationwide prospective study on patients with Crohn’s disease and ulcerative colitis treated with Infliximab-biosimilar CT-P13 in a real-life setting: two-year follow-up of the ReFLECT study

Abstract Background ReFLECT study was carried out to investigate real-life use of CT-P13, the first monoclonal antibody biosimilar to infliximab (IFX) originator. Methods This multicentre, prospective, observational study was conducted in France to assess characteristics of patients (pts) receiving CT-P13, its effectiveness and safety in a real-life setting. Eligible were both pts who had been switched from IFX originator (IFXS) and IFX-naïve pts started on CT-P13 (IFXN). These interim descriptive statistical analyses are about pts with Crohn’s disease (CD) and ulcerative colitis (UC). Results Among the 1370 adult pts included between October 2016 and April 2019, data were analysed for 508 CD pts (48.6% males; mean age ± SD: 37.7±13.7; median [Q1;Q3] disease duration: 6.2 [1.9;13.7] years; 323 IFXN/145 IFXS) and 213 UC pts (54%; 42.9±17.2; 5.4 [1.6;12.8]; 154 IFXN/46 IFXS). Previous biologics other than IFX were taken by 32.9% of CD and 39.0% of UC pts; 31% (CDS) and 23% (UCS) of pts were switched from IFX originator to CT-P13. At the time of the first administration of CT-P13, disease had been more active in IFXN vs IFXS pts: 52.9% vs 13.3% in CD with a median [Q1;Q3] Harvey Bradshaw Index (HBI) of 4 [1;8] vs 1 [0;2] and, 82.9% vs 33.3% in UC with a median Mayo Score of 7 [3;10] vs 2 [0;4]. In IFXS pts, disease activity remained stable after 2 years of treatment with median differences of HBI and Mayo score since first administration of 1 [0;2] and 0 [-4;1]. In IFXN pts, median differences of HBI and Mayo score since first administration were -2 [-7;1] and -7 [-8;-5]; CT-P13 brought disease activity down to levels below or comparable to those seen in IFXS pts. Reasons for CT-P13 withdrawing and safety data are reported in Tables 1 and 2. Conclusion Year 2 follow-up data indicate that CT-P13 effectively induced improvement in disease activity in IFXN pts with CD or UC and maintained stable activity in IFXS pts. This real-life study did not highlight any new safety concerns.

P587 Utility of intestinal ultrasound in Inflammatory Bowel Disease patients on management decisions

Abstract Background Intestinal Ultrasound (IUS) has been gaining momentum in the management of patients with inflammatory bowel disease (IBD). Underutilized in the United States(U.S.), we present the impact of IUS in management decisions in a cohort of IBD patients seen at a tertiary center. Methods This retrospective study analyzed all IBD patients seen at our institution undergoing IUS as part of routine clinical evaluation. Patient demographics, disease type, clinical activity, laboratory markers, and therapy was obtained. Patients with evidence of inflammation based on IUS characteristics of bowel wall thickening, with additional parameters of mural stratification, mesenteric fat, doppler flow, lymph nodes, dilated bowel, free fluid used as adjunct measures were compared to those without IUS features of activity. Subsequent management plan based on findings were evaluated. Results Of 148 patients seen for IUS (median age 41 (range 18–81), 67% female), 108(73%) had Crohn’s disease (CD), 39(26.4%) had ulcerative colitis (UC), 1(0.7%) had IBD-undetermined (IBD-U) with 111(75%) Caucasians, 9.5% Blacks, 8.8% Asians, and 6.8% Hispanics. Median disease duration was 8 years, range (0–43) with 113(94.1%) on biologic/small molecule therapy and 7(5.8%) on mesalamines. No differences in BMI were noted in those with active disease vs. those in remission. However, we noted 29(19.3%) had fatty liver on ultrasound, which correlated highly with high BMI (31 vs. 24) in those with normal liver (p&amp;lt;0.05). On IUS, 110(66%) of our patients had evidence of disease activity and 56(34%) were in remission. Inflammatory markers ESR and CRP did not correlate to IUS activity. In our UC patients Mayo score correlated to IUS findings but not Harvey Bradshaw Index (HBI) for CD. For those with positive findings on IUS, 29.5% escalated therapy for their IBD, and 13.3% required change in drug mechanism. For those in remission, the majority of patients 43(84.3%) continued their therapy while 3(5.9%) successfully de-escalated therapy. Conclusion In our study, IUS was useful in providing management decisions in those with active disease especially as there was a lack of correlation to inflammatory markers and HBI scores.

P441 Clinical efficacy, drug sustainability and results from therapeutic drug monitoring in Crohn’s disease patients treated with ustekinumab – 1-year follow-up of a prospective, nationwide, multicenter cohort from Hungary

Abstract Background Although efficacy and safety of ustekinumab (UST) in the treatment of inflammatory bowel disease have been demonstrated through randomized trials, data from real-life prospective cohorts are still of great interest. Our aim was to evaluate the clinical efficacy, drug sustainability, frequency of dose intensification, and results from therapeutic drug monitoring in UST treated Crohn’s disease (CD) patients using a prospective, nationwide, multicenter cohort from Hungary. Methods Patients were consecutively enrolled in this cohort between 2019 January and 2020 May from 5 academic centers and 5 county hospitals. Data from patient demographics, disease phenotype, treatment history (surgical history, prior and present medical therapies), clinical disease activity (using the Crohn’s Disease Activity Index (CDAI), Harvey Bradshaw Index (HBI)), biomarkers (C-reactive protein – CRP), and therapeutic drug monitoring were captured. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. Results N=142 CD patients were included with a median follow-up time of 60 weeks (IQR:47.5–79.5w) [57.4% female; age 38.4±13.0 years]. Based on the Montreal classification, complicated disease behavior (B2orB3) was 48.2%, whereas ileocolonic disease location(L3) 55.7%. Perianal manifestation was present in 46.8% of the patients. Previous anti-TNF exposition was 97.2%, while previous vedolizumab failure was 25.5%. 66.2%/ 66.9% of the patients had moderate-to-sever clinical disease activity at baseline (CDAI&amp;gt;220/HBI&amp;gt;7). Clinical response and remission rates were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores after induction treatment (w8). One year clinical remission rates were 58% / 57.3% (CDAI/HBI) Composite clinical and biomarker remission (CDAI&amp;lt;150 and CRP&amp;lt;10mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Parallel corticosteroid use was 34%/26.3%/16.5%/21%/16.9% at baseline and w8/w16-20/w32-36/w52-56. Drug sustainability was high with 81.9% (SD: 3.4) of patients remaining on treatment at one year.(Figure1) Probability of dose intensification was high and introduced early in the treatment, 42.2% (SD: 4.2) at ~w32 and 51.9% (SD: 4.4%) at 1y.(Figure2) Patients with complex disease phenotype (B2/B3) had higher probability for dose intensification (log-rank: p=0.042). Mean serum trough levels of UST were 4,28±3,35/ 1,35±1,42/ 0,82±0,65 and 1,13±0,74µg/mL measured at w8/w16-20/w32-36 and w52-56. ADAs were exceeding 1AU/mL in only 2 patients. Conclusion Ustekinumab showed good drug sustainability and clinical efficacy in a population with severe disease phenotype and high rates of previous anti-TNF failure, however frequent and early dose intensification was required.

P555 Outcomes of multiswitching from original infliximab to biosimilars in patients with inflammatory bowel disease

Abstract Background Since 2013 multiple Infliximab (IFX) biosimilars became available in the market. While there is evidence that switching from original IFX (RemicadeÒ) to an approved biosimilar product is safe and effective, little is known about outcomes of reverse switching and multiple switching among biosimilars in IBD patients. As the access to biosimilars at competitive prices increases, it is necessary to evaluate multiple switches to provide data on their interchangeability. Our aim was to evaluate the efficacy, safety and pharmacokinetic profile in a cohort of IBD patients who experienced multiple switches. Methods This is a cohort retrospective observational study, enrolling patients with IBD who were successively switched from original IFX to one or more biosimilars (multiswitching). We compared clinical disease activity, assessed using the Harvey-Bradshaw index (HBI) and partial Mayo Score (pMS), biochemical markers (hemoglobin, C-reactive protein (CRP) and albumin), IFX trough levels (ITL) and anti-IFX antibodies (ADA) immediately before and after multiswitching. Adverse and infusion-related events leading to drug discontinuation were registered. Results We included 26 patients (59% male, mean age 35±12 years), 85% (n=22) with Crohn’s Disease (CD) and 15% (n=4) with ulcerative colitis (UC) or indeterminate colitis. The mean disease duration from diagnosis was 9±6 years. According to Montreal classification, most patients were A2 (68%), had ileocolonic disease (L1 51%; L2 9%; L3 50%) and an inflammatory phenotype (B1 41%; B2 23% and B3 36%). Perianal disease was present in 44%. Half of patients had pancolitis (E3). About 51% of the patients had a prior resection surgery and 27% was on combination therapy when the first switch occurred. In 35% (n=9) of the patients three switches were observed. The mean follow-up from the first switch was 15±18 months. There was no significant difference in the proportion of patients in clinical remission (HBI &amp;lt; 5; Mayo score &amp;lt; 3) (91% vs 96%, p=NS). We found no differences in laboratory markers such as CRP (0,79 vs 0,67 mg/dl, p=NS), hemoglobin (13,83 vs 13,75g/dl, p=NS) and albumin (3,98 vs 4,37mg/dl, p=NS) before and after the multiswitching. No significant difference was observed in mean ITL (4,9 vs 4,05 μg/mL, p=NS) or in the proportion of patients with ITL&amp;gt;3ug/ml (p=0.205). None of patients developed ADA, infusion-related events or loss of response leading to drug discontinuation. During our follow-up none of patients was operated. Drug persistence was 100%. Conclusion In our cohort, no significant changes in efficacy, safety or immunogenicity were observed when IBD patients experienced multiple switches between the original IFX and its biosimilars.

P470 Ustekinumab Trough Levels are not Associated with Clinical Response in Inflammatory Bowel Disease Patients

Abstract Background Ustekinumab (UST) has been shown to effectively induce and maintain remission in inflammatory bowel disease (IBD). Only a few studies thus far have focused on UST pharmacokinetics suggesting that both, trough levels after i.v. induction as well as trough levels during stable maintenance might be associated with clinical and endoscopic response to UST. Data from real-world cohorts in this setting are scarce. Therefore, the aim of our study was to assess whether clinical response to UST was associated with a specific pharmacokinetic pattern. Methods All IBD patients treated with UST in one tertiary IBD centre between January 2017 and August 2020 were retrospectively retrieved from the database. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. Clinical response was defined as a decrease of HBI of ≥2 points or partial Mayo score ≥3 points. Patients not responding to therapy by week 16, or loosing original response received dose escalation from 90mg s.c. every 8 weeks to 90mg every 4 weeks. UST through levels were assessed by commercially available ELISA kit (IDKmonitor®) at week 8 after i.v. induction and/or during maintenance therapy after a minimum period of 16 weeks of treatment. Results In total, 61 IBD patients were included (mean age 38 years, range 22–70; 38 women; 54 CD/6 UC/1 IBD-U). All patients were antiTNF experienced, minority (11; 18%) had also been treated with vedolizumab prior UST. Thirty-nine pts (64%) were responders, out of these 15 pts (38%) required dose escalation at some point of the treatment due to secondary loss of response. UST through levels at week 8 were significantly higher than the maintenance levels (mean 5.6±SEM 0.7µg/mL vs. 2.2±0.3µg/mL; p&amp;lt;0.001). There were no significant differences between responders and non-responders neither in trough levels after induction (5±0.8µg/mL vs. 6.4±1.1µg/mL, p=n.s.), nor in trough levels during maintenance therapy (2.3± 0.4µg/mL vs. 1.9 ±0.4µg/mL, p=n.s.). Patients requiring dose escalation did not differ from stable responders in maintenance trough levels (2.4±0,6 µg/mL vs. 2,3 ±0,4 µg/mL). Conclusion In this limited size real-world cohort of IBD patients, we found no difference in pharmacokinetics between reponders and non-reponders to ustekinumab.

P461 Vedolizumab Dose Escalation in a Real-World Cohort of IBD Patients

Abstract Background Vedolizumab (VDZ) effectively induces and maintains remission in inflammatory bowel disease (IBD). The loss of response to VDZ has been shown to be recaptured with dose escalation but the data in this field are still scarce. In addition, data on pharmacokinetics (PK) of dose escalation are limited and it is unclear whether PK should used in decision-making algorithm in adjusting VDZ dose regimen. Therefore, the aim of our study was to assess clinical efficacy and pharmacokinetic profile of VDZ dose escalation. Methods All IBD patients treated with VDZ in one tertiary IBD centre were retrospectively retrieved from the database. According to local protocol, non-responders to standard dosing of 300 mg i.v. of VDZ every 8 weeks, received escalated dose of 300mg i.v. every 6 or 4 weeks. Disease activity was assessed by Harvey-Bradshaw index (HBI) and partial Mayo score in Crohn’s disease (CD) and ulcerative colitis (UC) pts; respectively. VDZ dose was escalated in case of clinically assessed primary non response by week 22 of the treatment or in case of secondary loss of response. Response to dose escalation was defined as a decrease of HBI of ≥2 points, partial Mayo score ≥3 points or endoscopic improvement. VDZ through levels were assessed at the completion of induction and in dose escalated patients after at least two VDZ administrations in shortened interval. Results In total, 75 IBD patients were included (mean age 47 years, range 20–90; 36 men; 35 CD/39UC/1 IBD-U). Fifty two pts (69%) were primary responders, out of these 23 pts (44%) required dose escalation at some point of the treatment due to secondary loss of response. Out of 23 primary non-responders, 10 stopped the treatment, the remaining 13 received escalated dose of VDZ. Altogether, dose escalation was used in 36 pts (48%). There were no differences in the proportion of CD and UC between conventional and escalated dose regimen groups. Among secondary loss of response, the response was recaptured in 15 out of 23 pts (65%} while only two out of thirteen primary non-responders responded to dose escalation. There were no significant differences in VDZ levels between pts requiring dose escalation and pts with stable response to conventional regimen (mean levels 9,97±1,276 vs. 12,79±1,771 µg/mL; p=n.s.). VDZ levels increased significantly in patients who responded to dose escalation (from 10,12±3,460 to 20,81±3,326 µg/mL; p=0.0497). Conclusion Response to vedolizumab can be successfully recaptured in two thirds of secondary non responders by dose escalation. Patients requiring dose escalation do not seem to differ from stable responders with regards to vedolizumab pharmacokinetics.

P432 MyChart application in addressing Inflammatory Bowel Disease patients’ concerns and impact on service utilisation

Abstract Background MyChart is a novel electronic portal within the electronic patient record provider EPIC. IBD patients were asked to complete an electronic questionnaire via MyChart prior to their infliximab infusions. A threshold was set that any patient who recorded a severe disease activity score (Mayo &amp;gt;/3, Harvey-Bradshaw Index (HBI) &amp;gt;/8) or signalled a concern created an automatic message that was routed to our clinical nurse specialists. Methods Electronic notes of all IBD patients who received infliximab in the month of September 2020 were reviewed. Demographics, activity status of My Chart, type of concerns raised and outcomes, number of inpatient admissions and outpatient appointments pre- and post- the introduction of the online questionnaire were recorded. Clinical remission was defined as Mayo score of &amp;lt;3 or HBI score of &amp;lt;5. Statistical comparisons were performed in GraphPad Prism software using the exact Fisher’s test and student t-test accordingly. Values were deemed significant if p&amp;lt;0.05. Results 140 IBD patients on infliximab were identified; 2 were excluded due to incomplete data. The cohort comprised of 77 males (55.8%) with mean age of 27 years (SD of 15.1).110 (78.70%) patients had a diagnosis of Crohn’s disease whereas 24 (17.0%) had ulcerative colitis and 4 (2.8%) unspecified type IBD. 104 (75.1%) patients were active on MyChart and 83 (58.9% of total; n=138) completed the infliximab questionnaire. Significantly fewer of the patients active on MyChart required scheduled outpatient reviews when compared to those that were inactive (59.6% vs 94.1%; p=0.0001; Table 1). There were no significant differences in terms of demographics, IBD type or clinical remission between the two groups. Strikingly, patients who did not fill in the questionnaire were significantly more likely to have scheduled outpatient review in comparison to those that filled it (83.6% vs 67.4%; p=0.047) despite a higher proportion of the first being in clinical remission at baseline (86.6% vs 67.4%; p=0.047). Furthermore, we evaluated the impact of introducing the online questionnaire by looking at the outpatient reviews and inpatient admissions before and after patients filled it in. The group was significantly less likely to require outpatient reviews (67.5% vs 87.3%; p=0.0061) or inpatient admissions (6.0% vs 17.5%; p=0.03) following introduction of the online questionnaire (Figure 1). Conclusion Overall, patients active on MyChart seemed to be significantly less likely to require outpatient review. This impact seemed particularly evident after filling in an online questionnaire which effectively addressed patient concerns and prevented unwarranted outpatient reviews and inpatient admissions.

Randomized Controlled Trial of Cognitive-Behavioral and Mindfulness-Based Stress Reduction on the Quality of Life of Patients With Crohn Disease.

Patients with Crohn disease have debilitating psychological symptoms, mental fatigue, and poor quality of life. Psychological intervention may improve these symptoms. We performed a randomized parallel-group physician-blinded trial of cognitive-behavioral and mindfulness-based stress reduction (COBMINDEX) on quality of life and psychological symptoms in adults with mild-moderate Crohn disease. COBMINDEX was taught by social workers in one-on-one video conferences over 3 months; quotidian home practice was mandated. Fifty-five COBMINDEX and 61 waitlist control patients completed the study; mean age was 33 years and 65% of participants were women. At 3 months, COBMINDEX patients had significantly reduced disease activity (per Harvey-Bradshaw Index score, C-reactive protein level, and calprotectin level), increased quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ] score increased from baseline 41 to 50; P < 0.001), decreased psychological symptoms (Global Severity Index [GSI], 0.98-0.70; P < 0.001), reduced fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue, 26-33; P < 0.001), and increased mindfulness disposition (Freiburg Mindfulness Inventory, 33-38; P < 0.001). Waitlist patients had a significant but small change in Harvey-Bradshaw Index, SIBDQ, and GSI scores, without improvement in fatigue or mindfulness. There were significant correlations (0.02 > P < 0.002) in COBMINDEX patients between baseline SIBDQ, GSI, Freiburg Mindfulness Inventory, and Functional Assessment of Chronic Illness Therapy-Fatigue scores with a relative change (baseline to 3 months) of the SIBDQ score, but none among waitlist patients. Predictors of relative change of the SIBDQ score in COBMINDEX patients included the GSI score (90% quantile; coefficient 0.52; P < 0.001), somatization (90%; 0.20; P = 0.001), depression (75%; 0.16; P = 0.03), and phobic anxiety (75%; 0.31; P = 0.008). COBMINDEX was effective in increasing patients' quality of life and reducing psychological symptoms and fatigue. Patients with severe baseline psychological symptoms benefited the most from COBMINDEX.

Effects of Gastric Neuromodulation on Crohn’s Disease in Patients With Coexisting Symptoms of Gastroparesis

Crohn's Disease (CD) results from chronic inflammation of the gastrointestinal (GI) tract involving TNF-α release. Gastrointestinal electrical stimulation (GES), a form of neuromodulation used to treat upper GI motility symptoms (UGI Sx), exerts an anti-inflammatory effect via TNF-α suppression. We hypothesized patients with CD symptoms in patients with gastroparesis (GP) may respond to GES. We retrospectively examined 284 patients with symptomatic gastroparesis (Gp Sx), who underwent GES placement. Patients with Gp Sx were evaluated by validated GI Sx patient reported outcome. Scores were obtained at baseline, after temporary GES placement and after permanent GES placement. Eleven patients from this cohort with coexisting CD were analyzed for improvements in their CD symptomatology using the Harvey Bradshaw Index (HBI). HBI scores were compared from before GES to after two sequential applications of electrical stimulation (temporary then permanent). A 3-point decrease in HBI indicated a clinical response and an HBI <5 indicated clinical remission after GES. An unadjusted repeated measures model was used in the analysis with statistical significance set at p ≤ 0.05. Our cohort prevalence of CD was 3.9% (2 M & 9 F, mean age 49.8 yrs.). Within both the Gp + CD & Gp subgroups, UGI Sx substantially improved after temporary and permanent GES. Furthermore, 55% of the GP + CD subgroup demonstrated a clinical response by HBI, while one patient achieved clinical remission (p < 0.01). CD medications were reviewed before and after GES placement, and any interval changes are unlikely to explain the improved HBI scores. We conclude that both UGI and CD symptoms in GP + CD patients responded well to GES. The interaction of Gp and CD and the effects of neuromodulation on CD symptoms warrant additional investigation.