Tertiary Inflammatory Bowel Disease Center Research Articles

Latent profiles of fatigue in inflammatory bowel disease

IntroductionFatigue is prevalent in people with inflammatory bowel disease (IBD) and has been associated with IBD activity, sleep quality, depression, and anxiety. This study aimed to identify fatigue profiles or clusters through latent profile analysis.MethodsAn online questionnaire was administered through three tertiary IBD centres, social media and through Crohn’s Colitis Australia. Fatigue was assessed via the Functional assessment of chronic illness measurement system fatigue subscale (FACIT-F), a validated assessment of fatigue and its severity. Validated measures of anxiety, depression, IBD activity and sleep quality were also included. Latent profile analysis was performed including fatigue, sleep quality, active IBD, and depression and anxiety. The relationships between profiles and IBD and demographic data were investigated.ResultsIn a cohort of 535 respondents, 77% were female, the median age was 41 years (range 32–52 years), and the majority had Crohn’s disease (62%). Severe fatigue was seen in 62%. Latent profile analysis identified four distinct profiles differing by fatigue score - low fatigue, at-risk profile, active IBD, and a poor mental health profile. Female gender, obesity and opioid usage were associated with higher risk of being in the active IBD and poor mental health profile. Age over 40 was associated with lower risk of being in the poor mental health profile.ConclusionLatent profile analysis identifies four classes of fatigue in an IBD cohort with associations with specific risk factors for fatigue along with specific IBD and demographic attributes. This has implications for the classification of fatigue in IBD and treatment algorithms.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis.

Real-world data on tofacitinib (TOF) covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis (UC) are scarce. To investigate the long-term efficacy and safety of TOF treatment for UC, including clinical issues. We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center. All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled. Patients were followed up until August 2020. The primary outcome was the clinical response rate at week 8. Secondary outcomes included clinical remission at week 8, cumulative persistence rate of TOF administration, colectomy-free survival, relapse after tapering of TOF and predictors of clinical response at week 8 and week 48. The clinical response and remission rates were 66.3% and 50.5% at week 8, and 47.1% and 43.5% at week 48, respectively. The overall cumulative clinical remission rate was 61.7% at week 48 and history of anti-tumor necrosis factor-alpha (TNF-α) agents use had no influence (P = 0.25). The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8 (30.9% vs 88.1%; P < 0.001). Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8 (odds ratio: 0.61, 95% confidence interval: 0.45-0.82, P = 0.001). Relapse occurred in 45.7% of patients after TOF tapering, and 85.7% of patients responded within 4 wk after re-increase. All 6 patients with herpes zoster (HZ) developed the infection after achieving remission by TOF. TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α agents. Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF. Special attention is needed for tapering and HZ.

Burden of Mental Health among Patients with Inflammatory Bowel Disease-A Cross-Sectional Study from a Tertiary IBD Center in Hungary.

Background: Inflammatory bowel diseases (IBDs) are chronic conditions that negatively affect the patient's quality of life. With the spread of the biopsychosocial model, the role of mental health in the activity and course of inflammatory bowel disease is becoming more and more recognized. Our study aimed to assess the prevalence of anxiety and depression in IBD patients in our tertiary referral center and determine the predictive factors of these mental conditions. Methods: A total of 117 patients were included consecutively between 1 December 2021 and 28 February 2022. We used a questionnaire to gather demographic information, disease course, and IBD-specific symptoms. We assessed anxiety symptoms using the GAD-7 and depressive complaints using the PHQ-9 questionnaire. We evaluated disease activity using CDAI and pMayo scores. Results: Of the 117 patients (male/female: 63/54), 88 suffered from Crohn's disease, and 29 were diagnosed with ulcerative colitis. Only 6 patients were taking medication for mood disorders, and 38 individuals sought mental support during their lifetime. A total of 15% of the population suffered from moderate-severe anxiety disorder, and 22% were affected by moderate-severe depression. The GAD-7 and PHQ9 values showed a significant correlation between the number of stools, bloody stools, abdominal pain, number of flare-ups, and CDAI scores. Conclusions: Our study confirmed that there is a high incidence of anxiety and depressive symptoms among IBD patients. Our results highlighted the symptoms that could be associated with mental disorders. It is important to assess the mental status of IBD patients to improve their quality of life.

Patient engagement and satisfaction with early phase cell therapy clinical trials at a tertiary inflammatory bowel disease center

Several clinical trials are underway investigating cell and gene therapy, and while these trials are meant to significantly impact patient care, they rely on patient engagement and participation. Unfortunately, clinical trials generally require extensive commitment by subjects. While several studies are using validated surveys to measure patient-reported outcomes, there is a lack of characterization of the patient experience as a subject in these trials. As such, we surveyed mesenchymal stromal cell (MSC) trial participants to understand their perspective. We found that there exists a reliance on one's gastroenterologist and colorectal surgeons for trial introduction and that time and cost were the main barriers to participation. Overall, participants demonstrated high satisfaction with MSC trial participation, but future protocols could incorporate increased use of virtual appointments to optimize patient experience.

TELEHEALTH ENHANCES RETENTION OF PATIENTS WITH INFLAMMATORY BOWEL DISEASE WITHIN A TERTIARY CARE INFLAMMATORY BOWEL DISEASE CENTER

Abstract INTRODUCTION Telehealth care in the ambulatory setting has dramatically increased in the COVID and post-COVID period in medicine. Understanding how this may impact the care of patients (pts) with inflammatory bowel disease (IBD) is important. This study aims to evaluate the pattern of use of telehealth care in a tertiary care IBD center. METHODS Pts seen at a tertiary care IBD center from January 2018 to March 2020 and August 2020 to January 2023 were included. Pts seen between March 2020 and July 2020 were excluded as the institution had mandatory telehealth visits during this period. Data was obtained from the Electronic Medical Record after IRB approval. Office visit types were based on billing codes, and office visits were only included in the analysis if seen by an MD or Advanced practice provider (APP). Drive time in minutes (min) was established from pt addresses using Esri geographic information systems (GIS) data, services and software. All new pts seen in the IBD Center are required to be seen in-clinic. After August 2020, pts seen in follow up can be seen at an in-clinic visit or via telehealth at the patient’s preference. Statistical analysis included Pearson Chi Square analysis for categorical variables and z-tests for means comparisons for continuous variables. RESULTS A total of 7,040 pts included. 56% were female. 89% were white, 7% Black or African American, and 76% had commercial health insurance, 17% had Medicare, 4% Medicaid, and 3% had no health insurance. New pts seen in the post-Covid period had shorter drive times than those seen in the pre-Covid period. (Table 1) Pts who had at least one year of follow up were more likely to be seen as a return visit in the post-Covid period vs the pre-Covid period (84% vs 76%, p&amp;lt;0.05). In the post-Covid period, 62% (3,575/5,750) pts had return IBD care by their MD or APP team delivered via telehealth. Pts seen in telehealth had significantly longer drive times than in-clinic-only pts (median 56.3 min [IQR 93.3] vs median 47.9 min [IQR 89.7]), p&amp;lt;0.001. (Table 2) This was significant for both the telehealth pts who had been seen in-clinic in the pre-Covid period as well as pts who were seen only in the post-Covid period. Pts who continued care only with in-clinic visits in the post-Covid period had significantly shorter drive times than pts who were seen in-clinic pre-Covid (38.8 min [IQR 60] vs 54.2 min [IQR 89.9]), p&amp;lt;0.001. CONCLUSION Telehealth is an effective strategy for continued multidisciplinary care at a tertiary care IBD center. More than half of patients continuing to participate in telehealth for follow up care, and patients were more likely to follow up in the post-Covid period. Patients who live farther away are more likely to continue IBD care via telehealth. Table 1 Overall Drive Time for New patients in the Pre- and Post-COVID periods Table 2 Drive Times for Return patients in the Pre-Covid and Post-Covid periods

P784 Efficacy of ustekinumab in biologically naïve patients with Inflammatory Bowel Disease

Abstract Background In recent years, there are several new treatment options for inflammatory bowel disease (IBD). Tumour necrosis factor α inhibitors have been joined by novel advanced therapies (vedolizumab, ustekinumab (UST) and Janus kinase inhibitors). These drugs are mostly used as second-line treatments after tumor necrosis factor α inhibitors, with subsequent poorer efficacy. There are few data available on the efficacy of first-line treatment with UST. The aim of our study was to assess efficacy of UST in biologically naïve patients with IBD. Methods All patients older than 18 years who had a confirmed diagnosis of IBD, treated in a tertiary IBD centre (University Medical Centre Ljubljana, Slovenia), who started first-line treatment with UST, were included in this retrospective cross-sectional cohort study. Demographics, clinical characteristics of patients, treatment persistence of UST, clinical disease activity scores, C-reactive protein (CRP), faecal calprotectin (FC), UST concentrations, and endoscopic scores were collected retrospectively in medical files. We determined a Kaplan-Meier curve of treatment persistence. Results We included 71 patients, 11 of which had ulcerative colitis and 60 had Crohn’s disease. Persistence of treatment with UST in biologically naïve patients is 88% at one year (Figure 1). Clinical remission was achieved in 57.7% of patients. Biochemical remission was achieved in 77.6% (CRP&amp;lt;5mg/ml) and 71.1% (FC&amp;lt;100mg/kg) of patients. Endoscopic remission (Mayo endoscopic score &amp;lt;2 in ulcerative colitis or absence of ulcers in Crohn’s disease) was achieved in 50.0% of patients. There was no significant difference (P&amp;gt;0.05) between the median serum concentrations of UST in the group of patients who achieved remission (clinical (5.86μg/ml), biochemical (5.93μg/ml based on CRP, 5.63μg/ml based on FC) and endoscopic (7.14μg/ml)) and who did not achieve remission (5.31μg/ml, 3.25μg/ml, 4.47μg/ml and 4.64μg/ml, respectively). Conclusion Treatment of UST in biologically naïve IBD patients shows high treatment persistence with high biochemical and endoscopic remission rates. It appears that UST is more efficacious if used as first-line therapy compared to the use after other advanced therapies. Further prospective data are needed to confirm our findings.

P831 Acute infusion reactions due to different biologic agents in a large cohort of patients with Inflammatory Bowel Disease

Abstract Background The therapeutic armamentarium for inflammatory bowel disease (IBD) includes several biological agents: infliximab (IFX), adalimumab (ADA), vedolizumab (VED) and ustekinumab (UST). Persistence in therapy with these drugs is not satisfactory, not only due to the loss of clinical response over time but also due to adverse events. Acute infusion reactions (AIRs) occur during or within 24 hours of the infusion. The intensity of AIRs ranges from mild (flushing, dizziness, headache, itching, rash) to severe (anaphylactic). The primary aim of this study was to compare the prevalence rates of AIRs due to the different biological agents in a large cohort of patients with IBD and to assess risk factors for AIRs. Methods All reports of AIRs occurring from January 2021 to October 2023 in IBD patients treated with different biological agents (IFX, ADA, VED and UST) in a tertiary IBD center were retrospectively reviewed. The electronic records of the identified patients were checked for the type of IBD, whether Crohn's disease (CD) or ulcerative colitis (UC), type of biological agent, route of administration (intravenous or subcutaneous), concomitant immunosuppressive therapies, atopic status. Furthermore, the type of treatment for the AIRs and the subsequent therapy undertaken for IBD were also recorded. Results 22 AIRs were recorded out of 1911 patients (1.1%). Of these, 16/550 in patients on IFX biosimilars (2.9 %), 4/590 (0.7%) in patients on ADA biosimilars, 2/318 (0.6%) in patients on VED and 0/453 (0%) in patients on UST (Table 1). The difference in the prevalence of AIR rates observed with the different biological agents was statistically significant (p&amp;lt;0.01). 7 of 16 post-IFX AIRs were moderate-severe, with two episodes of anaphylaxis occurring in patients with CD. The two patients treated with VED experienced only mild symptoms, and no anti-reactive treatment has been used; two mild and two moderate AIRs, respectively, have been reported among patients on ADA. 12 of 22 AIRs occurred during the induction period (from the first to the third administration). 7 of 22 patients had previous allergic reactions. Conclusion Our real-world data on a large population of IBD patients treated with biologic agents confirm that AIRs are rare and occur mainly in patients treated with IFX biosimilars. Most patients who experienced AIRs were atopic. Almost all patients after AIRs changed biological agents within or out of the same biological class. Further studies are necessary to confirm our results and better characterise the profile of patients at greater risk of AIRs.

P787 Use of upadacitinib to treat IBD in post-liver transplant

Abstract Background Approximately 2% of patients with inflammatory bowel disease (IBD) have concurrent primary sclerosing cholangitis (PSC). Liver transplantation (LT) is sometimes required due to progressive PSC. However, the management of active IBD post-LT is challenged due to concomitant anti-rejection immunotherapies. Janus kinase inhibition has been previously described to have anti-rejection properties in patients who have had renal transplants. Here, we describe our experience with upadacitinib (UPA), a selective Janus kinase-1 inhibitor, for post-LT active IBD combined with anti-rejection immunosuppression therapy. Methods This is a retrospective, single-center observational study in a tertiary IBD center. We identified patients with LT treated with UPA for their IBD. Patient related outcomes including transplanted liver status and clinical efficacy and safety of UPA for IBD activity were reviewed. Results We identified four patients (3 with Crohn’s disease, 1 with ulcerative colitis) treated with UPA after LT due to PSC, with the UPA indication for the treatment of IBD (n=3) and organ rejection (n=1). Median follow-up was 3 months (interquartile range (IQR) 1.5-7.1), median age at starting UPA was 41.5 years (IQR 40-44), and median interval from the transplant was 3.2 years (IQR 2.3-5.6). Two patients with Crohn’s disease clinically responded to UPA, one weaned off prednisone 30mg/day and remained in clinical remission after reducing UPA from 30 mg/day to 15 mg/day. Two patients developed elevated AST/ALT of up to 107/57 U/L and 83/228 U/L; one required discontinuation of UPA at one month with subsequent AST/ALT normalization; the other remained on UPA with 1.5 month follow-up so far. One UC patient was treated with UPA combined with vedolizumab in an attempt to discontinue prednisone for their immunosuppression for organ rejection, however, they were unable to wean off prednisone due to recurrent ALT and Alk Phos elevations. One patient acquired a mild case of COVID-19 which resolved without change in therapy. No life-threatening adverse events were observed. Conclusion We describe 4 patients with IBD who had LT for PSC and who were treated with UPA with successful management of active IBD in 2 cases but lack of efficacy in one case and liver enzyme elevations limiting UPA use in a second. These findings support further exploration of this novel mechanism for treatment of IBD in the post-LT setting.

P494 Efficacy and safety of Upadacitinib in moderate to severe paediatric Crohn’s disease and ulcerative colitis in a tertiary Paediatric IBD (PIBD) centre – A case series

Abstract Background Upadacitinib is a selective Janus kinase 1 inhibitor approved for the treatment of patients 18 years and older with the diagnosis of Crohn’s disease and ulcerative colitis. Although there is promising data for its use in adult inflammatory bowel disease (IBD), limited data are currently available on its use in paediatric IBD. We present our experience in this case series of patients ≤ 18 years on Upadacitinib. Methods We identified patients under the age of ≤ 18 years, started on Upadacitinib for the indication of IBD. Data on demographics, disease subtype, duration on Upadacitinib, number of biologic failures, tofacitinib use, concomitant biologic use, adverse events and clinical remission were gathered. Results 12 patients with paediatric IBD (median age at Upadacitinib start 15.5 years, range 13.9 to 17.8 years, 8 (67%) males, were identified. 7 patients had Crohn’s disease, 3 patients had ulcerative colitis and 2 patients had IBD unclassified. 4 patients (33%) were diagnosed under the age of 6 years with early onset IBD (EOIBD), 1 was 3.5 years old, 1 was 4 years old and 2 were 5 years old. 11/12 (92%) patients had failed 3 or more biologics. Upadacitinib was used as monotherapy in all patients and previous biologic treatments were stopped. 1 patient with a partial response to tofacitinib was switched to Upadacitinib. All patients had active disease at commencement of Upadacitinib. All 12 (100%) patients were started on 45 mg of Upadacitinib. 8/12 (67%) patients have been followed up for at least 8 weeks. Out of the 8 patients, 5/8 (63%) patients were in clinical remission between 8-16 weeks of therapy, 2/8 (25%) had partial response and 1/8 (13%) has been refractory to treatment. Relapse of symptoms was noted in 1 patient after dose was dropped to 30 mg; this patient had achieved remission on 45 mg. No serious adverse events occurred; 2 patients noted to have increased triglycerides (max 5.75mmol/L; range 0.38-1.58mmol/L). 1 of them had previous exposure to tofacitinib and the triglycerides were already raised prior to starting Upadacitinib. 1 patient developed headaches, as a result, Upadacitinib dose was decreased. There were no incidences of shingles or other serious infections. Abbreviations CD, Crohn's disease; UC, ulcerative colitis; IBD-U; inflammatory bowel disease unclassified; Upa, upadacitinib; AEs; adverse events Conclusion The patients in this case series, started on Upadacitinib, are a heterogeneous group with refractory disease. In these paediatric and adolescent patients Upadacitinib seemed safe and efficacious with a low side effect profile. Further national and international collaborative studies are needed to confirm our findings. Table 1. Patient Characteristics

Transitioning patients from intravenous to subcutaneous infliximab and vedolizumab for inflammatory bowel disease: what is the opportunity cost of improving access to healthcare?

Biologic drugs are highly effective for inflammatory bowel disease (IBD) management but are key drivers of costs of care especially when administered intravenously (i.v.). Availability of subcutaneous (SC) formulations has increased convenience for patients and improved access to care, but at the cost of revenue to health services. To evaluate the economic impact of transitioning a tertiary centre IBD cohort from i.v. to SC biologic administration and assess the implications for key stakeholders. A retrospective analysis of all patients who received i.v. infliximab or vedolizumab in the outpatient infusion centre of a tertiary IBD centre between July 2019 and June 2021 was undertaken. Data were collated from electronic medical records, pharmacy dispensing systems and the hospital business intelligence unit. An economic analysis and theoretical financial/capacity impact analysis of a transition to an SC model were estimated under two scenarios using a random 10% and 30% of the patient cohort. Transitioning our IBD cohort from i.v. to SC administration would result in a loss to our health service of AU$2 732 123.75, composed of AU$1 463 003.75 in Weighted Inlier Equivalent Separation (WIES) and AU$1 269 120 in drug procurement revenue. However, it would ease capacity in the infusion centre by up to 5256 h. Transitioning patients to SC administration results in improved access to infusion centres and substantial savings to state governments; however, switching results in a loss of i.v. biologic-generated WIES to health services. Alternative funding models are required to achieve sustainability in IBD care and reduce reliance on i.v. biologic-generated income.

HOSPITALIZATION, USE OF BIOLOGICS AND SURGERY RATES IN INFLAMMATORY BOWEL DISEASES: A SINGLE-CENTRE COMPARATIVE ANALYSIS BETWEEN PUBLIC AND PRIVATE HEALTHCARE SYSTEMS IN A TERTIARY UNIT FROM LATIN AMERICA.

Inflammatory bowel diseases (IBD) have rising incidence and prevalence rates globally. In IBD, there are scarce stu-dies comparing differences between patients according to socioeconomic status. Our aim was to comparatively evaluate hospitalizations, use of biologics and rates of surgery in patients with IBD between public and private healthcare systems. Single-center retrospective cohort study in patients with IBD from a tertiary referral unit from Latin America, between 2015 and 2021. CD and UC patients were classified into two subgroups: public and private systems. Demographic characteristics, hospitalizations, need for surgery and biologics were compared. A total of 500 patients were included, 322 with CD and 178 with UC. CD-related hospitalizations were frequently observed in both healthcare systems (76.28% in private and 67.46% in public). More than half of the patients had been submitted to one or more CD-related abdominal surgery, with no significant difference between the subgroups. Although there was no difference in the rates of use of biological therapy in CD subgroups, infliximab was more used in the public setting (57.69% vs 43.97%). There was no difference in UC-related hospitalizations between the subgroups (public 30.69% and private 37.66%) as well as the rates of colectomy (public: 16.83%, private: 19.48%). Biologics were prescribed almost twice as often in private as compared to public (45.45 vs 22.77%). There were no differences in the rates of hospitalization and abdominal surgery between the systems. In patients with UC, there was greater use of biological therapy in the private healthcare setting. • In a tertiary IBD center in Latin America. • More than half of the patients had been submitted to one or more CD-related abdominal surgical procedure. • Between the two healthcare systems, there was no difference in the rates of use of biological therapy in patients with CD, and in UC-related hospitalizations. • Biologics were prescribed almost twice as often in the private system as compared to the public in patients with UC.

Factors influencing the healthcare transition in Chinese adolescents with inflammatory bowel disease: a multi-perspective qualitative study

BackgroundThe development and implementation of the transition from pediatric to adult healthcare systems for adolescents with inflammatory bowel disease (IBD) should consider stakeholders’ perceptions. This study aimed to explore the factors influencing the transition of Chinese adolescents with IBD from the perspectives of patients, parents, and healthcare providers.MethodsA descriptive qualitative research was conducted. Purposive sampling was used to recruit 36 participants, including 13 patients, 13 parents, and 10 providers, from a tertiary pediatric IBD center, a tertiary adult IBD center, and the China Crohn’s & Colitis Foundation in Zhejiang Province, China. Individual semi-structured interviews were used to collect data on facilitators and barriers to the transition process. Conventional content analysis was used to analyze the interview transcripts.ResultsNine primary themes were identified. Patients with young age, prolonged disease duration, severe disease, academic pressures such as the Gaokao, low level of disease acceptance, limited transition consciousness, low self-efficacy, poor transition communication, and inadequate medical transition system serve as barriers. While patients with the mentality of guilt towards their parents; parents with low education levels and intensive work schedules, high levels of disease acceptance, and situations of parent-child separation; stakeholders with high transition consciousness, high transition self-efficacy, and effective transition communication act as facilitators. Furthermore, community support and hospital guide services were also contributing factors during the transition.ConclusionsThis study offers comprehensive insights into the factors affecting the transition of Chinese adolescent IBD patients. The process is continuously influenced by stakeholders, community, and healthcare environments and policies. Identifying these factors provides healthcare providers with a reference for developing and implementing targeted transition interventions.

Focal loss of mural stratification as a radiological predictor for small bowel adenocarcinoma in Crohn's disease

AimPatients with Crohn's disease (CD) are at higher risk of small bowel adenocarcinoma (SBA). We aimed to identify radiological predictors of SBA in CD. MethodsWe conducted a retrospective case-control study at two tertiary inflammatory bowel disease centers and identified CD patients diagnosed with SBA between 2003 and 2019. Patients were matched with up to four controls. Pre-operative imaging (magnetic resonance imaging (MRI) or computed tomography (CT)) were reviewed by three gastrointestinal radiologists. ResultsNineteen patients with CD-associated SBA with a mean age of 54.9 and 32 matched controls were included. Mean length of small bowel involvement was 216 (± 188) mm in the SBA group versus 156 (± 167) mm in the control group (p = 0.76). Only 11.8 % of cases had a diagnosis of SBA made preoperatively. In univariate analysis, focal loss of mural stratification (odds ratio [OR], 11; 95%CI, 2.43–49.5, p = 0.002), and wall thickening (OR, 1.32; 95%CI, 1.05–1.66, p = 0.02) were significantly associated with SBA. After adjustment, focal loss of mural stratification was the only independent risk factor (OR, 11; 95 % CI, 2.43-49.5, p = 0.002). ConclusionsFocal loss of mural stratification was identified as a predictor of CD-associated SBA, which should be described in imaging reports and further validated.

Insomnia is common in inflammatory bowel disease (IBD) and is associated with mental health conditions as well as IBD activity.

Insomnia is common in people with chronic medical conditions, such as inflammatory bowel disease (IBD), and is readily treatable through cognitive behavioral therapy for insomnia. This study aimed to describe the associations with insomnia in people with IBD and its relationship to IBD-related disability. An online questionnaire was administered through 3 tertiary IBD centers, social media, and Crohn's Colitis Australia. The questionnaire included the Insomnia Severity Index (ISI), a validated assessment of insomnia. Measures of anxiety, depression, physical activity, and disability were also included. IBD activity was assessed using validated patient reported scores. A multivariate model was constructed for clinically significant insomnia and ISI scores. Subpopulations of Crohn's disease and ulcerative colitis were considered. In a cohort of 670 respondents the median age was 41 years (range, 32-70 years), with the majority female (78.4%), the majority had Crohn's disease (57.3%). Increasingly severe disability was associated with worse insomnia score. Clinically significant insomnia was associated with clinically active IBD, abdominal pain, anxiety, and depression, in a multivariate model. In an ulcerative colitis population, Simple Clinical Colitis Activity Index components of general well-being and urgency were associated with worse ISI score in a model including depression and anxiety. In those with Crohn's disease, the multivariate model included Harvey Bradshaw Index score in addition to depression and anxiety. Insomnia is common in people with IBD and is associated with increased disability. Abdominal pain and mental health conditions should prompt consideration for screening for insomnia and referral for cognitive behavioral therapy for insomnia.

Higher Adalimumab Trough Levels Are Associated with Histologic Remission and Mucosal Healing in Inflammatory Bowel Disease.

(1) Many patients with inflammatory bowel disease (IBD) in endoscopic remission have persistent histologic activity, which is associated with worse outcomes. There are limited data on the association between adalimumab drug concentrations and histologic outcomes using validated histologic indices. We aimed to assess the relationship between adalimumab concentrations and the Robarts Histopathology Index (RHI). (2) Patients from a tertiary IBD center from 2013 to 2020 with serum adalimumab (ADA) trough concentrations measured during maintenance therapy (≥14 weeks) and a colonoscopy or flexible sigmoidoscopy with biopsies performed within 90 days of drug level were included. Blinded histologic scoring using the RHI was performed. Primary analysis assessed the relationship between adalimumab drug concentrations and histologic remission using receiver operating characteristic curve analysis. (3) In 36 patients (26 Crohn's Disease, 9 ulcerative colitis, 1 indeterminate), median adalimumab concentrations were higher (17.3 ug/mL, 12.2-24.0) in patients with histologic remission compared to those without (10.3 ug/mL, 6.8-13.9, p = 0.008). The optimal ADA concentration identified using the Youden threshold was ≥16.3 ug/mL (sensitivity 70%, specificity 90%). Patients with ADA ≥ 16.3 ug/mL had higher histologic remission rates (78%) compared to lower ADA concentrations (14%, p= 0.002), as well as higher mucosal healing rates (86%) compared to lower levels (12%, p = 0.001). Symptoms correlated weakly and non-significantly with both histologic (RHI) scores (r = 0.25, p = 0.2) and adalimumab concentrations (r = 0.05, p = 0.8). (4) The current study demonstrated that higher serum adalimumab concentrations (≥16.3 ug/mL) are needed for histologic remission and mucosal healing assessed using the RHI.

Vedolizumab does not increase risk of clostridium difficile infection in patients with inflammatory bowel disease using vedolizumab: A retrospective cohort study

IntroductionSeveral studies have shown increased incidence, recurrence, and severity of Clostridium difficileinfection (CDI) over the last decade. Patients with inflammatory bowel disease (IBD) who develop CDI are more prone to morbidity and mortality than CDI in patients without IBD. This study seeks to evaluate whether IBD patients who use vedolizumab are at increased risk of CDI compared to IBD patients using other therapies. MethodsThis was a retrospective cohort study, and 684 patients with confirmed IBD (228 on vedolizumab, 228 on anti-TNF, and 228 on 5- Aminosalicylates acid therapy) were enrolled from January 2009 to August 2019 at a tertiary referral IBD center at McMaster University Medical Centre (MUMC) in Hamilton, Ontario, Canada. The primary outcome was time to the development of CDI in IBD patients using different therapies. Secondary outcomes included rates of CDI and the association between baseline variables and risk of CDI. A Cox proportional hazards (PH) model was used to evaluate baseline factors and development of CDI. ResultThere was no difference in time to CDI between the three treatment groups (log rank p-value 0.37). CDI occurred in 16 patients (2.3%), specifically four patients (1.75%) in the vedolizumab group, four patients (1.75%) in the anti-TNF group, and eight patients (3.5%) in the 5-ASA group. The Cox PH model found current smoking, older age, and concomitant immunomodulator use as risk factors for CDI, after adjustment for other covariates. Vedolizumab was not associated with increased risk of CDI in the model. ConclusionBiologic therapy with vedolizumab or anti-TNF did not impact risk of CDI. Risk factors for CDI in IBD patients included smoking, older age at the onset of medication, and immunomodulator therapy. Clinicians should have high degree of suspicion for CDI in IBD patients presenting with diarrhea, particularly in those with risk factors identified in this study.

Upadacitinib Salvage Therapy for Infliximab-Experienced Patients with Acute Severe Ulcerative Colitis.

Acute severe ulcerative colitis [ASUC] is a medical emergency treated with intravenous steroids followed by infliximab or cyclosporin in the case of steroid failure with emergent colectomy required in refractory or severe cases. Case series have reported on the effectiveness of tofacitinib for refractory disease, but data regarding the effectiveness of upadacitinib in this setting have not been previously reported. We describe the use of upadacitinib therapy for steroid-refractory ASUC in patients with prior loss of response to infliximab. Six patients who received upadacitinib for steroid-refractory ASUC were identified at two Australian tertiary inflammatory bowel disease centres. Patients were followed for up to 16 weeks after discharge with clinical, biochemical and intestinal ultrasound [IUS] outcomes. All six patients demonstrated clinical response to upadacitinib induction during their inpatient admission. Four patients achieved corticosteroid-free clinical remission by week 8, including complete resolution of rectal bleeding and transmural healing assessed by IUS, and sustained clinical remission at week 16. One patient proceeded to colectomy at week 15 due to refractory disease. No adverse events directly attributable to upadacitinib were identified. Upadacitinib may have a role as a safe and effective salvage therapy for steroid-refractory ASUC in patients who have previously failed to respond to infliximab therapy. Prospective studies are required to determine the safety and efficacy of upadacitinib use in this setting before routine use can be recommended.

Role and Impact of a Clinical Pharmacy Team at an Inflammatory Bowel Disease Center

There is limited literature describing the role of a clinical pharmacy team within a tertiary academic inflammatory bowel disease (IBD) center. The goal of this paper is to describe and showcase the clinical and operational impact of an integrated clinical pharmacy team. This was a retrospective study evaluating the referral outcomes for all patients referred to University of Chicago Medicine Specialty Pharmacy for self-administered advanced IBD therapies covered by prescription insurance from October 1, 2020 to October 31, 2021. A total of 1800 referrals were received for advanced IBD therapies. Prior authorizations (PAs) were required and submitted for 1700 referrals. Of those 1700 PA submissions, 297 (17%) were denied by insurance. To overturn the denials, 344 appeals, including second-level appeals and external reviews, were submitted. Manufacturer patient assistance programs were obtained for 69 patients. From the 1800 referrals, 98% of patients were successfully started on the intended therapy. Clinically, there were 2141 pharmacist-initiated interventions by 2 IBD pharmacists. The most common interventions were prevention in interruption of therapy and providing patient education. Clinical pharmacy teams are well positioned to streamline care within a tertiary academic IBD center. Their unique skillset and ability to provide high yield medication access supports the use of this model as a best practice in IBD centers.

Serrated polyps in patients with ulcerative colitis: Unique clinicopathological and biological characteristics.

Serrated polyps have recently been reported in patients with ulcerative colitis (UC); however, their prevalence and detailed characteristics remain unclear. The prevalence and clinicopathological and biological characteristics of serrated polyps in patients with UC were retrospectively examined in a single tertiary inflammatory bowel disease center in Japan from 2000 to 2020. Among 2035 patients with UC who underwent total colonoscopy, 252 neoplasms, including 36 serrated polyps (26 in colitis-affected segments, 10 in colitis-unaffected segments), were identified in 187 patients with UC. The proportion of serrated polyps was 1.8% (36/2035). Serrated polyps in colitis-affected segments were common with extensive colitis (88%), history of persistent active colitis (58%), and long UC duration (12.1 years). Serrated polyps in colitis-affected segments were more common in men (88%). Of the 26 serrated polyps in colitis-affected segments, 15, 6, and 5 were categorized as sessile serrated lesion-like dysplasia, traditional serrated adenoma-like dysplasia, and serrated dysplasia not otherwise specified, respectively. Sessile serrated lesion-like dysplasia was common in the proximal colon (67%) and with BRAF mutation (62%), whereas traditional serrated adenoma-like dysplasia and serrated dysplasia not otherwise specified were common in the distal colon (100% and 80%, respectively) and with KRAS mutations (100% and 75%, respectively). Serrated polyps comprised 14% of the neoplasias in patients with UC. Serrated polyps in colitis-affected segments were common in men with extensive and longstanding colitis, suggesting chronic inflammation in the development of serrated polyps in patients with UC.

P481 Visceral fat to skeletal muscle area ratio predicts for Ustekinumab loss of response.

Abstract Background Loss of response (LOR) to anti-TNFα therapy in inflammatory bowel disease (IBD) is common and biologic therapies such as anti-IL12/23 agents have shown greater durability in efficacy. Anti-TNFα LOR is increased in higher body mass index (BMI) patients however the evidence for the association between body composition or BMI and Ustekinumab’s (Ust) therapeutic response is limited, with the latter not impacting clinical efficacy in the ‘IM-MUNITI’ post-hoc analyses. This study’s primary aim was to evaluate the impact of body composition on time to LOR to Ustekinumab in Crohn’s disease (CD) patients. Methods 99 adult CD patients aged ≥16 yrs. from two tertiary IBD centres were studied retrospectively. Included patients had received Ust ≥12 weeks, abdominal imaging (CT or MRI) within 6 months of Ust induction, and documented follow up until 30th April 2022. A single experienced abdominal radiologist blinded to the clinical information measured the area of visceral fat (VFA), skeletal muscle (SMA), and subcutaneous fat at the mid L3 vertebral level. Each compartment was corrected for height2 to derive visceral fat (VFI), skeletal muscle (SMI) and subcutaneous fat (SFI) indices. VFA:SMA ratio was also calculated. Clinico-demographic details including therapeutic and surgical history were recorded. Kaplan Meir survival analyses, univariate and multivariate cox regression analyses were performed to evaluate factors predictive of Ust LOR. Results 99 patients met the inclusion criteria with mean age (±SE) 46.6yrs (±1.6) and 49 (49.5%) male. 63 (63.6%) patients were bio-experienced. Univariate Cox regression analyses of age, sex, BMI, peak C-reactive protein (CRP) and nadir Albumin level within 3 months of the CT/MRI scan, disease duration, prior biologic failure and concurrent immunomodulator used within 6 months of Ust induction showed that none of these were predictive of Ust LOR (P&amp;gt;0.05). There was a numerical trend for the middle VFI tertile (40.01-79.99cm2/m2) to having a lower risk for LOR compared to the lowest and highest VFI tertile (Fig. 1a), (HR=0.37, 95%CI= 0.13, 1.11, P=0.08), as well as a higher SMI for having a lower risk of LOR (Fig. 1b), (HR= 0.6, 95%CI= 0.24,1.31, P= 0.18), but these were not statistically significant. A higher VFA: SMA ratio however, was a significant predictor of LOR (HR=2.98, 95%CI 1.2,7.3, P= 0.02) (Fig. 1c), which persisted when it was adjusted on multivariate analysis for age, sex, albumin, CRP, BMI, disease duration, prior biologic failure and concurrent immunomodulator use (HR= 10.6, 95%CI 2.8-39.8, P=&amp;lt;0.0001). Conclusion The ratio of VFA:SMA, but not BMI, is a superior predictor of losing response to Ustekinumab.