bluuebunny/crossref_metadata_2025_split huggingface dataset:
P404 Underrepresentation of minorities and lack of race reporting in ulcerative colitis drug development clinical trials
Authors: Sedano R , Hogan M , McDonald C , Aswani-Omprakash T , Ma C , Jairath V 
Published: January 2022

Abstract

Background
Historically, inflammatory bowel disease (IBD) trials report high enrollment rates for white-caucasian patients. To promote initiatives towards diversifying patients enrolled in clinical trials, we assessed the reporting of race/ethnicity of patients enrolled in pharmaceutical clinical trials for ulcerative colitis (UC).

Methods
A previous systematic review of all placebo-controlled trials in adult patients with UC examining different therapeutic drug classes was performed from inception to December 2020.
Trial and patient characteristics were summarized according to the type of variable. Categorical variables were summarized by displaying the number and percentage of trials or participants for each category. Continuous variables were summarized by displaying the weighted mean, weighted standard deviation, and range. Means and standard deviations (SD) were weighted by the number of participants in each trial.

Results
Descriptive statistics of trial and patient characteristics for, 95 induction trials and, 29 maintenance trials are summarized in Table, 1. Race was reported in, 37.9% (36/95) of induction studies, with most participants being White (86.3%;, 8610/9976). Furthermore, 21/36 (58.3%) studies reported race as White vs. non-White participants; and, 15/36 (41.7%) studies provided further breakdown, including Black (115/3414 patients [3.4%]), Asian (448/4136 patients [10.8%]), and “Other” (127/4136 patients [3.1%]). Moreover, 3/36 studies misreported race as ethnicity and, only, 3/36 studies reported ethnicities correctly, classifying patients as Hispanic/Latinx vs. Non-Hispanic/Latinx. For maintenance trials, 34.5% (10/29) studies reported race, with majority of participants being White (85.6%;, 2778/3246). Additionally, 6/10 studies reported only a White vs. non-White participants comparison, while, 4/10 reported other races, including Black (45/1145 patients [3.9%]), Asian (40/888 patients [4.5%]), and “Other” (26/1145 patients [2.3%]). No studies reported ethnicity.

Conclusion
Given the increasing burden of IBD in developing countries, differences amongst racial and ethnic groups are important to understand since they can influence disease phenotype, response to therapy, and safety outcomes.1 We found poor race reporting in UC clinical trials and observed that the vast majority of participants enrolled were White. These findings suggest that the population prevalence of UC amongst different racial groups is not reflected in clinical trial populations, being important to raise awareness of the existing barriers that prevent patients from accessing clinical trials. Reporting of race and ethnicity in UC clinical trials should be mandatory, and a requirement to enroll a certain percentage of non-White patients should be considered.2
P412 Drug persistence and endoscopic, histologic and biochemical remission rates among patients following ileal pouch-anal anastomosis treated with biologic therapy: Results from a prospective patient cohort
Authors: Ollech J , Yanai H , Avni-Biron I , Snir Y , Banai H , Broitman Y , Goren I , Wasserberg N , White I , Dotan I 
Published: January 2022

Abstract

Background
Patients with ulcerative colitis (UC) after total proctocolectomy and ileal pouch-anal anastomosis (IPAA) may develop chronic pouchitis or Crohn’s like disease of the pouch (CLDP). These patients may need treatment with biologic therapies. Data regarding treatment persistence as well as clinical, biochemical, endoscopic, and histologic remission rates are lacking

Methods
Patients after IPAA were followed prospectively at a dedicated pouch clinic. Patients with CP or CLDP who were antibiotic/steroid-refractory or dependent, had antibiotics/steroids side effects or had extraintestinal manifestations were treated with biologics. Clinical, endoscopic, histologic, and laboratory data were extracted from medical records at the last follow-up. Patient’s quality of life (QoL) was assessed by visual analog scale (VAS), with scores of, 0–100 (higher=better QoL). Time to biologic therapy discontinuation was measured for all patients; patients were censored if still on biologic therapy at the time of the last follow-up. Biochemical remission was defined as C-reactive protein (CRP)&lt;, 0.5 mg/dl and a fecal calprotectin (FC)&lt;, 150 ug/dl with a normal albumin level. Endoscopic and histologic remission was defined by the pouchitis disease activity index (PDAI) as an endoscopic subscore ≤2 and a histologic subscore, 0 or, 1, respectively.

Results
The prospective cohort constituted, 130 patients. Females:, 73 (56%). Before IPAA, most (70%) patients had pancolitis, 95% received steroids and mesalamine, and, 37% - biologic therapies. Median follow-up after ileostomy closure:, 16 years. Biologic therapy was started in, 28 patients (22%) due to CP or CLDP. The first line biologic for all, 28 patients was anti-TNF’s and, 9 patients received more than one line of biologics. Median time to commencing biologics:, 130 months. Median first-line biologic drug persistence:, 222 weeks. Among patients treated with biologic therapy, at the last clinic visit, median CRP was, 0.58 mg/dl, median FC:, 255ug/g, median HB:, 12.46 mg/dl, and median albumin was, 4.5 mg/dl.Median PDAI endoscopic and histologic scores were, 2; median VAS rating was, 80. Biologic remission criteria were fulfilled by, 43% of patients (N-12). An additional, 43% (N-12) were also in endoscopic remission with an endoscopic PDAI subscore of, 2 or below, and an additional, 29% of patients (N-8) were in histologic remission with a histologic PDAI score of, 0 or 1.

Conclusion
Biologics reintroduction after IPAA was relatively common, albeit after a very long interval. Biologic therapy was effective, with a sizable proportion of patients in biochemical, endoscopic, and histologic remission. Likewise, drug persistence was long. We suggest that early initiation of biologic therapy in certain patients may be prudent.
P424 Uptake of a switching program for patients receiving intravenous infliximab and vedolizumab to subcutaneous preparations
Authors: Alice H , Gemma B , Selinger C P 
Published: January 2022

Abstract

Background
Recent trials support the clinical efficacy and safety of subcutaneous (sc) biologic treatment for IBD maintenance therapy. Administration of sc injections could reduce the financial burden and time required to attend for infusions and allow IBD service providers to manage increasing clinical demand. We evaluated the uptake and rationale for choosing to switch from intravenous (iv) infusions to sc injections, including the impact of the Covid-19 pandemic on IBD service provision.

Methods
All adult patients receiving standard dosing maintenance iv Infliximab or Vedolizumab therapy at a tertiary IBD centre were offered a switch to the respective sc formulations. We investigated the uptake of the switch from iv infusions to sc injections and utilised a standardised patient questionnaire to determine the rationale for switching to sc injections or not, and to identify areas for improvement in IBD service provision for the switching process.

Results
In a cohort of, 232 eligible patients (258 total patients, 190 infliximab, 68 vedolizumab, 26 no longer eligible), 58% of patients receiving Infliximab and, 59% of patients chose to switch to sc treatment. Of the, 26 ineligible patients, 6 were switched to an intensified treatment schedule, 12 switched to a different biologic, 2 moved out of area, 5 had treatment stopped for clinical reasons and, 1 required operative treatment. There were no significant predictors for willingness to switch relating to patient age, sex, diagnosis, drug, line of treatment or duration of treatment (p&gt;0.05). Early results from patient questionnaires (n=23) demonstrate that a decision to switch was not influenced by the impact on their mental health, Covid-19 risk, the impact on wider IBD service provision or financial savings, but, 70% of switchers did report that time savings influenced their decision. A minority of patients reported feeling pressured to switch (10% switchers and, 15% non-switchers) or had concerns about the safety (20% switchers, 0% non-switchers) and efficacy (40% switchers, 31% non-switchers) of sc injections. The majority of patients feel they were provided with sufficient

Conclusion
Switch uptake rates were, 58% with, 90% of patients eligible to switch. We found no evidence that a decision to switch was influenced by age, sex, diagnosis, drug, line of treatment or duration of treatment. Non-switchers value face-to-face support at the IBD unit highly, and switchers value the time saved by administering injections at home. Switching to sc formulation not only provided patients with a choice of saving time usually required for iv administration but also reduced pressure in an overstretched IBD service.
P427 Exploring phenotype and treatment of inflammatory bowel disease in the elderly
Authors: Gaglani R , Balarajah S , Williams H , Hicks L 
Published: January 2022

Abstract

Background
On a background of an ageing population, approximately, 10–15% of new cases of IBD are diagnosed in patients over the age of, 60.1,2 Studies show IBD in the elderly is increasing, including both the groups of patients diagnosed at a younger age, and de novo elderly IBD.
Older patients are more likely to have other co-morbidities and be concurrently prescribed other medications, which may impact the choice and timing of therapies for their disease. It is not clear if IBD in older age is different phenotypically from that in younger counterparts, and whether current management algorithms can be used safely in this cohort.
Aims of the study were to evaluate the IBD phenotype and use of therapies in the elderly (≥75 years) and younger (18–74 years) patients, and to assess for differences in adverse outcomes between both cohorts on immunosuppressants (IMs) and/or biologics.

Methods
A retrospective study was performed on, 173 IBD patients at Imperial College Healthcare NHS Trust over a two-year period., 91 elderly IBD patients were compared with, 82 younger patients, matched by gender and IBD subtype. Analysis included chi-squared tests with Fisher’s correction.

Results
There were, 55 elderly patients and, 51 younger matched patients with ulcerative colitis (UC) where no differences in disease extent, remission or surgeries were seen. There were, 36 elderly patients and, 31 younger matched patients with Crohn’s disease (CD). There was less ileocolonic disease in the older CD cohort compared to younger patients (27.8% versus, 51.6%, p=0.046) (figure 1).

Medication use in UC was the same regardless of age. There was significantly higher use of IMs and biologics in younger patients with CD (51.6%) versus the older cohort (25%, p=0.047) (figure 2).

In elderly patients with CD, a significantly greater mortality was seen in patients on IMs/biologics (27.3%) than those not on these medications (8%, p=0.023) (figure 3). The rate of VTE was higher (18.2% versus, 0%) in those on these treatments with a trend towards significance.

Conclusion
Overall, this retrospective study demonstrated that elderly IBD patients in this cohort appear to be mostly phenotypically similar to younger patients. However, elderly Crohn’s patients were less likely to be escalated to IMs/biologic treatments than their younger comparators. In view of the higher rate of adverse events recorded in the Crohn’s group managed with these treatments, this may be justified. Further, larger studies in the long-term outcomes of these patients are required.

Reference
1. Charpentier C et al. Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study. Gut., 2014;63(3),423–432
P443 Trough concentration response in infliximab and adalimumab treated children with IBD following treatment adjustment: A pharmacokinetic model
Authors: Levi R , Matar M , Zvoluni M , Shamir R , Assa A 
Published: January 2022

Abstract

Background
In patients with IBD, data on trough concentration (TC) response to adjustments in anti-TNFα treatment are scarce.

Methods
We included pediatric patients with IBD who were treated with anti-TNFα agents from, 2015 to, 2020 and had sequential monitoring of TC. Treatment adjustments were detected and subsequent changes in TC were recorded (next infusion for infliximab and up to, 8 weeks TC measurement for adalimumab). Patients with positive anti-drug-antibodies or with concomitant change in immunomodulatory treatment were excluded.

Results
For the entire cohort (86 patients), median age at diagnosis was, 13.2 (10.7–14.9) years (Females, 48%; Crohn’s disease, 72%). For infliximab, 58 patients had, 201 interval changes (98 decrease and, 103 increase) and, 26 had dose increase. Dose increase resulted in TC change in the same direction but TC changes could not be predicted due to significant variability (p=0.9). This variability could not be attributed to any specific variable.
Interval decrease: Median TC pre adjustment was, 4.3 mcg/ml (IQR, 3.1–6.9 mcg/ml). For every, 10% decrease in interval, TC was increased by, 1.6 mcg/ml (B=, 1.6, 95% CI;, 0.9–2.4; p&lt;0.001) or by, 57.2% (B=57.2, 95% CI;12.8–124.6; p=0.014). The presence of perianal disease was associated with attenuated response to interval decrease (diminished TC increase), p=0.001. Interval increase: Median TC pre change was, 12.6 mcg/ml (IQR, 9.5–12.1 mcg/ml). For every, 10% increase in interval, TC was decreased by, 0.66 mcg/ml (B=, 0.66, 95% CI;, 0.2–1.2; p=0.01) or by, 4.2% (B=, 4.2, 95% CI;, 2.0–6.4; p&lt;0.001). The diagnosis of Crohn’s disease (VS. diagnosis of UC) was associated with reduced response to interval increase (diminished TC decrease), p=0.012.
For adalimumab, 28 patients had, 31 events of interval decrease from every, 2 weeks to every week and, 12 events of interval increase back to every, 2 weeks. Interval decrease resulted in increased median TC from, 4.5 (3.5–5.3) mcg/ml to, 8.1 (6.5–10.5) mcg/ml (X1.8) while interval increase resulted in TC change from, 15.5 (12.8–18.6) mcg/ml to, 9.7 (6.5–14.6) mcg/ml (:1.6). Changes in adalimumab TC were consistently significant (p&lt;0.001). Increase in delta TC was associated with younger age (p=0.018), lower body surface area (p&lt;0.001) and with the absence of perianal disease (p=0.001).
Laboratory measures (CRP, albumin- mostly within normal limits) were not associated with TC response for both agents.

Conclusion
Changes in TC following treatment adjustment can be almost linearly predicted for adalimumab but not for infliximab. Thus, following infliximab adjustment, TC should be measured in-order to assess adequate TC response.
P444 COVID-19 risk factors, infection course and vaccination among patients with inflammatory bowel disease based on a Hungarian cohort
Authors: Farkas K , Matuz M , Kata D , Földesi I , Resál T , Bacsur P , Szántó K , Kolarovszki-Erdei D , Rutka M , Fábián A , Bor R , Szepes Z , Sarlós P , Miheller P , Zacháry A , Molnár T 
Published: January 2022

Abstract

Background
Inflammatory bowel disease potentially elevates the risk of infections, furthermore, disease activity and medical treatment(s) can increase the risk as well. However, both international data and recent studies do not confirm these preliminary conceptions regarding the SARS-CoV-2 infection. In addition, a number of studies have reported that less antibodies are produced against the virus in IBD patients. In January, 2021, the vaccination campaign has begun in Hungary as well, however, questions have been raised about the effectiveness and safety of the vaccine.

Methods
In this multicentre study, we assessed the prevalence and risk factors of COVID-19 infection, the willingness to receive COVID-19 vaccine and the efficacy of vaccination among IBD patients receiving biological therapy, based on a cross-sectional questionnaire-based study. To assess safety and antibody response to COVID-19 vaccines, we conducted a prospective study in the same Hungarian IBD centers. IgG antibody was quantified to SARS-CoV-2 spike protein and nucleocapsid, 1 week before and after the first vaccine and, 4 and, 8 weeks after the second vaccinane, respectively.

Results
472 patients were enrolled in the first part of our study. SARS-CoV-2 infection was confirmed in, 16.9% of patients. Wearing gloves and masks were found to be effective in preventing infection (p=0.02; p=0.005), avoidance of communal areas had no effect on infection rates. Male sex increased the risk (p=0.008) of viral infection. Based on subjective complaints, UC patients had a worse disease course (p=0.002). Biological therapies did not increase the risk of infections. Patients vaccinated with mRNA vaccine had a significantly higher spike protein antibody titer one month after the second vaccination (p=0.004) compared to other vaccine types (Sinopharm©, Sputnik V©, Astra Zeneca©). Seropositivity was detected in, 98% of patients. Sinopharm© vaccination triggered the lowest number of side effect (p&lt;0.001). SARS-CoV-2 infection induced relapses more frequently than vaccinations.

Conclusion
Face mask was the most effective preventive tool. The risk of infection was not increased by biological therapy, therefore therapy discontinuation is not justified. Almost every vaccinated patient developed seropositivity two month after vaccination independently from the type of the vaccine, however, spike protein antibody was significantly higher following mRNA vaccinations.
P446 Long-term Clinical Effectiveness And Stoma Outcome Of Fecal Diversion In Refractory Crohn’s Proctitis
Authors: Benammi S , Perry W R , Calini G , Abdalla S , Shawki S F , Larson D W , Mathis K L 
Published: January 2022

Abstract

Background
Proctectomy is often recommended when Crohn’s proctitis becomes refractory to medical therapy. However, some surgeons offer a temporary diverting stoma in an effort to avoid a permanent stoma. The long-term efficacy of this approach is not well-established. Our aim was to determine the long-term effectiveness of fecal diversion in patients with refractory Crohn’s proctitis.

Methods
This retrospective study included all patients with Crohn’s proctitis who underwent formation of a diverting ileostomy or colostomy for refractory disease from, 1998 to, 2019 in Mayo Clinic Rochester MN. Outcomes were disease recurrence, rate of stoma closure, and proctectomy. Univariate comparisons among categorical variables were performed with Pearson’s Chi-square and continuous variables using the student t-test. The cumulative probability of stoma closure was performed with a Kaplan Meier log-rank analysis. Multivariable analysis of risk factors for proctectomy and permanent stoma was achieved with logistic regression.

Results
Ninety-seven patients (55.7% female) were included. Ileostomy was the most common stoma type (88.7%, n=86), and colostomy was (11.3%, n=11) (Table.1). Median follow-up was, 4 years (range, 0–14). Active Crohn’s at follow-up was reported in, 68.1%. Only, 41.2% of patients underwent attempt at stoma reversal, and, 42.3% required a proctectomy (median, 19.5 months after diversion). At last follow-up, 29.9% were stoma-free, 42.3% had a new permanent stoma, and, 27.8% had the original diverting stoma (Fig.1). The multivariable predictors of proctectomy and permanent stoma were the recurrence of active CD after diversion and the need for other CD-related surgery following stoma creation (Table.2). The limitations of the study are its small sample size and its retrospective nature. The cumulative probability of stoma closure was performed with a Kaplan Meier log-rank analysis (Fig.2).

Conclusion
Diversion is effective at alleviating symptoms of Crohn’s proctitis in selected patients but does not significantly change disease outcome. Only a small number can avoid a long-term stoma.
P455 Aminosalicylates in Ulcerative Colitis: old but gold?
Authors: Sequeira C , Santos I , Coelho M , Teixeira C , Mangualde J , Cremers I , Oliveira A 
Published: January 2022

Abstract

Background
The clinical course of ulcerative colitis (UC) is characterized by periods of exacerbation and remission. 5-aminosalicylic acid (5-ASA) remains the treatment of choice in patients with mild-to-moderate UC, due to its beneficial effect in preventing relapse. Treatment options (immunomodulators [IMM] and biological agents) have increased, so it is important recognizing patients at risk of medical therapy failure that can appropriately optimize treatment escalation for better control of the disease. Little is known about the long-term course of the disease among patients in remission with 5-ASA.

Aims
To assess long-term efficacy of 5-ASA (no IMM, biological therapy or colectomy) and to identify predictive factors of non-response.

Methods
An observational, retrospective, single-centre, case-control study was performed. All consecutive patients with UC followed in our Hospital from January 2000 until June 2020 initially treated with 5-ASA (±steroids) with a minimum follow-up of 1 year were screened for eligibility. Exclusion criteria were 5-ASA toxicity/intolerance or initial treatment with IMM/biologic agents.Time until step-up was recorded. Demographic, clinical, endoscopic, biochemical, and histological variables at the diagnosis were recorded and a Cox regression was performed to identify predictive factors for step-up strategy.

Results
218 patients (mean age 41,4±14,6 years; 54,5% female; mean follow-up10,1±1,9 years) were analysed, 28% needed treatment with biologics or IMM, mainly due to steroid-dependence. Among “5-ASA responders”, 72% and 48% had sustained endoscopic and histological remission, respectively. The probability of step-up at 1 year, 5 years and 10 years was 10, 18 and 25%, respectively. “Step-up patients” had higher rates of hospitalization, disease extent progression, extraintestinal manifestations and colonic stenosis and/or pseudo-polyps (p&lt;0,05). Montreal E3 (HR:2,31;95% CI: 1,12-4,68), steroids at first flare (HR:3,45;95% CI: 1,26-7,29), lower 5-ASA maintenance dose (HR: 1,97;95%;CI:1,12-3,29), lower haemoglobin level (HR:1,45;95% CI: 1,11-3,24) and DUBLIN Score≥4 (HR:1,81;95% CI: 1,269-4,59) were factors associated with the step-up strategy, in multivariate analysis.

Conclusion
5-ASA is an effective maintenance therapy; a satisfactory response was achieved in 72% of the patients after a mean time of follow-up of 10 years.
Extensive colitis, higher DUBLIN Score, lower doses of 5-ASA, need for steroid and anaemia can predict a worse prognosis at the initial diagnosis and are associated with higher therapeutic requirements. These findings may be used in our clinical practice to identify patients that might benefit from an early step-up approach and minimize the morbidity associated with uncontrolled disease.