bluuebunny/crossref_metadata_2025_split huggingface dataset:
P433 Intravenous ustekinumab as maintenance treatment is effective in patients with partial or loss of response to optimized ustekinumab sc
Authors: Garcia-Alvarado M , Barrio J , Sierra-Ausin M , Arias L , Fernández-Salazar L , Fuentes Coronel A , Arias García L , García-Alonso F J , García-Prada M , Legido J , Sánchez-Hernández J G , Muñoz F 
Published: January 2022

Abstract

Background
Ustekinumab is an effective drug in Crohn′s Disease (CD) and most frequently used dose is subcutaneous (sc), 90 mg /, 8 weeks. With the usual sc doses (90 mg every, 8–12 weeks) some patients will only partially respond or experience secondary loss of response. In this situation, shortening of the administration interval (e.g., every, 4 or, 6 weeks) or a reinduction dose has been proposed. Another unexplored option is intravenous (IV) administration at regular intervals when shortening sc dose is not effective enough.

Methods
We conducted a retrospective study to evaluate the effectiveness of IV ustekinumab at regular intervals (usually every, 4–6 weeks) in patients with insufficient efficacy or loss of response to, 90 mg sc every, 4–6 weeks. All patients had active Ulcerative colitis (UC) or Crohn′s disease (CD) defined by partial Mayo score (pMS) or Harvey Bradshaw Index (HBI)&gt;, 4 points and/or persistent biomarker elevation (calprotectin&gt;, 250 µg/g) and/or endoscopic or radiological evidence of disease activity. We obtained data from, 79 patients (73 CD and, 6 with ulcerative colitis (UC)). Levels of fecal calprotectin before and after starting ustekinumab IV was available for, 44 patients and trough levels of drug for, 48 patients.

Results
Baseline characteristics of the included patients are shown in Table, 1. Complicated forms (B2-B3;, 60,6%) predominated and perianal disease was present in, 35.4% of patients. Only, 3 patients were naïve to biological treatments, 41.8% had received at least one and, 54,5% more than, 2. The mean follow-up after the first IV administration was, 13.22 months (IQR, 2–37 months). Last dose used before the start of ustekinumab IV was, 90 mg /, 6 weeks in, 31.6% and, 90 mg /, 4 weeks in, 68.4% of the patients.
After, 12 weeks of the first IV dose, 43% of patients achieve clinical remission (HBI&lt;5 or pMS, 2) and, 59.5% at the end of follow-up. Basal fecal calprotectin decreased significantly at month, 12 and at end of follow-up (612.6 mg/kg vs, 384.1 mg/kg vs, 222 mg/kg; p = 0.0002 and p=0,0048 respectively) (Figure, 1). Drug levels at the beginning of IV administration were, 2.6 mcg/ml (IQR, 0.13-11-69) and a significant increase from baseline was observed (week, 12–16:, 9.09 mcg/ml and after, 1 year:, 10.7 mcg/ml; both p &lt;0,001). At the end of the follow-up, 81% of patients maintain the treatment (figure 2).

Conclusion
Patients who lose response to the intensified dose of ustekinumab sc could benefit from intravenous administration as maintenance treatment. This strategy achieves clinical remission in, 60% of the patients and allows to maintain the treatment in, 80% of them for at least, 12 months.
P442 Real-world endoscopic and histologic outcomes are linked to ustekinumab exposure in Ulcerative Colitis
Authors: Alsoud D , Compernolle G , Tops S , Sabino J , Ferrante M , Thomas D , De Hertogh G , Vermeire S , Verstockt B 
Published: January 2022

Abstract

Background
Histologic healing is being proposed as new treatment target in ulcerative colitis (UC), and the concept of histo-endoscopic mucosal improvement was introduced in the UNIFI study with ustekinumab (UST) in moderate–to-severe UC. Very little is known about the Pk-PD relationship of ustekinumab in UC patients, and especially whether serum UST concentrations correlate well with colonic tissue drug exposure and with histologic healing. The aim of this study is to provide real-world data including histology, and to study UST serum concentrations and its relation to tissue levels and drug efficacy.

Methods
UC patients starting UST in standard dosage at our referral centre were prospectively followed by clinical and endoscopic assessments at week, 16 or week, 24, and colonic biopsies were taken for histopathologic scoring. Histologic remission was defined as Nancy histology index (NHI) of, 0. Other collected outcomes were clinical response, clinical remission, endoscopic improvement, endoscopic remission and mucosal healing (definitions in Figure, 1). Paired trough serum sample and colonic mucosal biopsy were collected for UST levels measurement using a CE marked in-house developed ELISA.

Results
A total of, 42 UC patients started ustekinumab between June, 2019 and May, 2021, allowing a follow-up of at least, 6 months (Table, 1). By week, 24, clinical response, clinical remission, endoscopic improvement, endoscopic remission, and mucosal healing were observed in, 31 (74%), 24 (57%), 22 (52%), 11 (26%) and, 10 (24%) patients, respectively (Figure, 1). Histologic remission was observed in, 19 (45%) patients, of whom, 10 and, 9 with endoscopic Mayo, 0 and, 1, respectively. Multivariate analysis identified clinical response at week, 8 as a predictor for histologic remission at week, 24 [OR, 8.84, p = 0.024], and inversely correlated with therapy discontinuation [OR, 0.10, p = 0.006]. A trend of higher UST serum trough levels was observed in patients achieving histologic and endoscopic outcomes in comparison with patients who did not reach these outcomes, with a significant statistical difference at week, 8 for endoscopic outcomes (Figure, 2). UST concentrations from paired serum and biopsy samples revealed a strong positive correlation (Spearman r=0.88, p&lt;0.001, n=17), both in inflamed (mayo endoscopic score &gt;1) (r=0.89, p&lt;0.001, n=10) and uninflamed (mayo endoscopic score ≤, 1) tissue (r=0.88, p&lt;0.008, n=7) (Figure, 3).

Conclusion
In this real-word cohort of UC patients initiating UST, more than a third of the patients achieved histologic remission. Serum UST levels were furthermore strongly correlated with tissue levels of UST. A drug exposure-response relationship was observed for histologic and endoscopic outcomes.
P454 Evaluation of the nutritional care status in italian centers managing patients affected by inflammatory bowel disease
Authors: Saibeni S , Bezzio C , Armuzzi A , Daperno M , Zanetti M , Vernero M , Giorgetti G M 
Published: January 2022

Abstract

Background
Patients affected by IBD are at risk for malnutrition. An impaired nutritional status is associated with several negative outcomes (increased risk of flares, poor response to therapy, hospitalizations, surgical interventions, and post-surgical complications). Nutritional care is defined as “the form of nutrition, nutrient delivery and the system of education that is required for meal service or to treat any nutrition-related condition in both preventive nutrition and clinical nutrition”. The aim of this study was to assess the current status of the nutritional care in the Italian Centers managing IBD patients.

Methods
A dedicated web-based questionnaire developed by the Italian Society of Artificial Nutrition and Metabolism (SINPE) was sent to all the 120 IBD Centers referring to IG-IBD. The relevance of the nutritional care was assessed using a Visual Analogue Scale from 0 (the less) to 100 mm (the most) and expressed as mean ± SD.

Results
63.3 (%) questionnaires were returned. The presence of an IBD-dedicated nutritionist is present in 27/120 (35.5%) Centers, while in 25/120 (32.9%) the evaluation of the nutritional status is considered hard to obtain. In 52 (68.4%) of Centers is present an IBD multidisciplinary team, in 22 of these (42.3%) a nutritionist is included. In the outpatient setting, the malnutrition risk is evaluated at each visit in 28 (36.8%) Centers, in case of active or complicated disease in 29 (38.2%) and only when the presence of malnutrition is suspected in 34 (44.7%). The nutritional status is evaluated at each visit in 28 (36.8%) Centers, in case of active or complicated disease in 38 (50.0%), while only when the presence of malnutrition is suspected in 31 (40.8%). In 67 (88.2%) Centers the evaluation of nutritional parameters is directly assessed by the gastroenterologist, by means of blood chemistry (98.7%), antropometric indices (82.9%) and impedenziometry (14.5%). For hospitalized IBD patients, the malnutrition risk and the nutritional status are evaluated at each admission in 37 (48.7%) and 42 (56.0%) Centers and only when the presence of malnutrition is suspected in 39 (51.3%) and in 37 (48.7%). The relevance of nutritional assistance in clinical management of IBD patients and in the institutional diagnostic and therapeutic paths were considered high by physicians: 86.5 ± 12.2 mm and 86.7 ± 13.1 mm, respectively.

Conclusion
Nutritional care for IBD patients appears quite far from being satisfactory in the Italian reality and at the same time highly wanted. Educational and logistic interventions are needed to improve the assessment and the treatment of malnutrition in the everyday clinic practice.
P456 Risk of malignant tumors in patients with autoimmune diseases on ustekinumab therapy: a systematic review and meta-analysis
Authors: Huang K , Zhang Y , Yao L , Zhang Z , Liu R , Cao Q 
Published: January 2022

Abstract

Background
Ustekinumab has shown efficacy in treating psoriasis, psoriatic arthritis, and inflammatory bowel disease and is generally safe in the short term; however, data on its long-term safety, especially in terms of malignant tumors, are lacking, which has aroused great public concern.

Methods
The PubMed, Web of Science, Embase, and Cochrane Library databases were searched from their establishment to July 2021 for randomized controlled trials (RCTs) reporting malignant tumors in adults with autoimmune diseases. Peto odds ratios (PORs) were calculated as effect sizes to assess the risk of malignant tumors.

Results
Fifteen RCTs involving 5835 patients were included in the study. The meta-analysis revealed that the risk of malignant tumors was not significantly different between patients treated with ustekinumab or placebo (POR=0.88, 95% confidence interval [CI] [0.37, 2.11], P=0.78). Similarly, no statistically significant difference existed in the incidence of non-melanoma skin cancers (POR=0.77, 95% CI [0.23, 2.61], P=0.68). No heterogeneity was observed in the comparisons.

Conclusion
Compared with placebo, ustekinumab did not increase the risk of malignant tumors or non-melanoma skin cancers in patients with autoimmune diseases, indicating the safety of this biological agent.
P468 Evaluation of work productivity and activity impairment in moderate-to-severe ulcerative colitis participants treated with ozanimod in the phase 3 True North study
Authors: Floden L , Pham T P , Kumar J , Becker B , Shaw J W , Tencer T 
Published: January 2022

Abstract

Background
Ulcerative Colitis (UC) is an autoimmune disease which negatively impacts patients’ quality of life including work performance. This study examined the effect of ozanimod on work productivity and activity impairment (WPAI) in participants with moderate-to-severe UC in the phase 3 True North study.

Methods
Participants who received 1 mg QD ozanimod during a 10-week Induction Period (IP) and were clinical responders from both placebo-controlled and open-label cohorts were randomised to ozanimod (n=230) or placebo (n=227) for a 42-week Maintenance Period (MP). Work productivity was measured with the WPAI-UC patient-reported outcome instrument that assesses absenteeism, presenteeism, work productivity loss, and activity impairment due to UC over the previous week. The WPAI-UC was administered at Weeks 10, 28, 40, and 52. Differences in WPAI-UC domain scores at the end of the IP were evaluated using t tests. Mixed-effects models for repeated measures (MMRMs) were fit to estimate least-squares mean WPAI-UC scores adjusted for treatment, time (categorical), clinical variables, and corticosteroid use at Week 10. MMRMs were also applied to evaluate differences in WPAI domain scores between groups defined by clinical response, clinical remission, and endoscopy score. Generalised estimating equation (GEE) models were applied to estimate the odds of improving or remaining stable (using a ≥7% change threshold) on WPAI-UC domains for those on ozanimod versus placebo. Missing values were multiply imputed using a placebo-based imputation model; estimates were combined using Rubin’s rules.

Results
At the end of the IP, the ozanimod group had significantly lower impairment of work productivity and activity (WPA) than the placebo group (Tab 1). During MP, the ozanimod group reported significantly lower levels of impairment for presenteeism (14.0% vs 20.2%; P=.003), work productivity loss (15.9% vs. 22.4%; P=.005), and activity impairment (15.4% vs 22.3%; P=.0001) compared to the placebo group (Tab 2). At Week 52, participants with improved endoscopy score, in clinical remission, or in clinical response had significantly lower impairment in all WPAI-UC domains (Tab 3). Participants in the ozanimod group showed increased odds of improving or remaining stable compared to those in the placebo group for all WPAI-UC domains (Fig 1).

Conclusion
Participants in the ozanimod arm had significantly better work productivity at the end of induction. Among participants who received ozanimod and achieved response in IP, ozanimod maintenance treatment was associated with improvements in WPA. These improvements were greater among participants who achieved clinical response or remission or improved endoscopic score.
P484 Do vedolizumab trough levels predict response to consecutive therapy in Inflammatory Bowel Disease?
Authors: Levartovsky A , Cohen I , Abitbol C M , Yavzori M , Fudim E , Picard O , Kopylov U , Ben-Horin S , Ungar B 
Published: January 2022

Abstract

Background
Vedolizumab trough serum levels have been associated with clinical and endoscopic response in patients with inflammatory bowel disease (IBD), albeit findings have not been conclusive. A recent study demonstrated that higher trough vedolizumab levels before therapy escalation predict optimal outcome. Our aim was to identify whether vedolizumab trough levels predict outcome of consecutive biologic or immunomodulatory therapy.

Methods
This retrospective study included IBD patients consecutively receiving vedolizumab therapy between November 2014 and June 2021 at Sheba Medical Center. Only patients who lost response to vedolizumab therapy, and had available trough levels prior to therapy cessation were included. Clinical and endoscopic scores, as well as drug retention, were recorded at 6 and 12 months post switching therapy.

Results
Overall, 66 IBD patients (36 CD, 30 UC) who lost response to vedolizumab therapy were included. They were treated with vedolizumab for a median of 47 weeks (IQR 31–85). Seventy-two percent of patients (48/66) were priorly treated with anti-TNF therapy (infliximab or adalimumab). After vedolizumab cessation, 66.7% of patients were switched to biologic therapy. These included 25.8% (17/66) to ustekinumab, 22.7% (15/66) to infliximab, 7.6% (5/66) to adalimumab, 6.1% (4/66) to certolizumab and 4.5% (3/66) to golimumab. The remaining 33.3% of patients switched to tofacitinib (10.6%), 5-ASA derivates or immunomodulator monotherapy (12.1%) or to a study therapy protocol (10.6%).
Median vedolizumab trough levels at therapy cessation were 32.25 μg/ml (IQR 12.8–61.4). Trough drug levels at therapy cessation were not associated with retention of biological or immunomodulatory therapy at 6 months [median 29.1 μg/ml (IQR 12.4–57.6) vs 33.8 μg/ml (IQR 27.9–58), p = 0.43] and at 12 months [median, 38.2 μg/ml (IQR 14.5–76.3) vs 30.1 μg/ml (IQR 11.5–45), p = 0.57] for patients who retained consecutive therapy versus those who did not.

Conclusion
Vedolizumab trough serum levels before therapy cessation due to loss of response do not predict retention of consecutive therapy.
P488 Trends in corticosteroid (CS) use over time and following diagnosis in patients with Inflammatory Bowel Disease (IBD), using IBM® MarketScan®
Authors: Raine T , Melmed G Y , Finney-Hayward T , Clark R , Chapman J C , Targownik L , Burisch J , Olen O 
Published: January 2022

Abstract

Background
As part of the IBD-DICE (Determinants, Incidence and Consequences of CS Excess) collaborative research programme, this study examined rates of CS use and excess use in patients with IBD over time and after initial diagnosis.

Methods
Using IBM® MarketScan®, a representative claims database including details of &gt;200 million individuals annually in the United States (US), we conducted a retrospective analysis of CS use from 2007 to 2018 in adult patients with IBD. Patients with conditions commonly associated with high levels of CS use (other than IBD) were excluded. CS use and excess were examined over calendar time in all patients (prevalent cohort), and in relation to the time of first IBD diagnosis in a newly diagnosed subset (incident cohort). Both a restrictive and a broader definition of CS use were examined. The restrictive definition only included claims for oral budesonide or prednisolone/prednisone with a pre-defined minimum daily equivalent dose of ≥17.5 mg, based on a typical tapering CS prescription for IBD. Under the broader definition, CS use was considered as any claim for oral prednisolone, prednisone, budesonide or methylprednisolone. Excess CS use was defined as either ≥2 CS courses in a 12-month period or ≥3 months of continuous CS use.

Results
The prevalent cohort (restrictive definition) included a total of 338,837 patients with 1,051,213 observation years. Rates of CS use ranged from 23.7% in 2007 to 19.3% in 2009 and plateaued in subsequent years (18.4%–21.1%). Rates of CS excess were higher from 2007 to 2009 (8.9%–11.5%) than in later years, and remained relatively stable from 2010 to 2018 (7.9%–8.6%). Similar patterns were seen with the broad definition of CS use, with CS excess rates of 15.2% in 2007 and 10.9%–11.8% from 2010 to 2018 (Figure 1). The incident cohort included 106,875 patients with 320,295 observation years. CS use was highest in the first year after diagnosis (24.2% and 29.4% with the restrictive and broad definitions, respectively) and decreased and plateaued by the second year after diagnosis (range: 10.8%–14.8% and 16.8%–21.0%, respectively). Similarly, CS excess was highest in the first year after diagnosis (11.7% and 14.6% with the restrictive and broad definitions, respectively) and decreased and levelled off by the second year after diagnosis (range: 3.6%–6.2% and 5.6%–8.6%, respectively) (Figure 2).

Conclusion
Despite advances in IBD treatment over the past decade and the adverse effects associated with CS, use of CS has not decreased substantially in the US in recent years. Levels of CS excess remain a concern, and may represent an opportunity for more optimised treatment and education, especially for newly diagnosed patients.
P554 Vedolizumab Associated quality of Life and inflammatory bowel disease control Upon Entering a subcutaneous switching program (VALUE) – Results from a multi-centre UK study
Authors: Lim S , Gros Alcade B , Lehmann A , Lindsay J , Gaya D , Caulfield L , Dhar A , Ritchie S , Limdi J , Taylor J , Raine T , Balendran K , Shuttleworth E , Kwok J , Cococcia S , Murray C , Walker G , Aldridge R , George B , Colbert R , Dawson P , Jameson E , Irving P , Sharma E , Lees C , Samaa M 
Published: January 2022

Abstract

Background
Vedolizumab, a gut-selective monoclonal antibody targeting α4β7-integrin, was recently licenced as a subcutaneous (SC) preparation after demonstrating efficacy compared to placebo at maintaining remission in IBD patients who had a clinical response to intravenous (IV) induction therapy. We aimed to assess real-world experience of switching patients to SC administration.

Methods
Patients across 10 UK centres who had completed induction with IV vedolizumab were offered SC therapy. Demographic data and baseline disease characteristics (disease type and behaviour, medication history) were collected, alongside biochemical markers (C-reactive protein, faecal calprotectin), disease activity scores (SCCAI, partial Mayo or modified Harvey Bradshaw Index) and quality of life scores (IBD-Control-8) at baseline (defined as the first dose of SC medication), 8 and 24. Data was also collected on drug persistence, hospital admissions, steroid use and reported adverse events.

Results
351 patients were switched to SC dosing. All had data collected for weeks 0 and 8 and 164 had data at week 24. There were no statistically significant differences in biochemical markers, disease activity scores or quality of life at weeks 0, 8 or 24, nor were there statistically significant differences in rates of biochemical remission or clinical remission.
Subcutaneous vedolizumab persistence at week 24 was 86% (141/164), with discontinuation due to disease activity (n=9), adverse events (n=11), non-compliance (n=2) and pregnancy (n=1). Of the 23 who discontinued SC, 12 switched back to IV (4 of whom at an escalated dose), 4 changed to another biologic and 7 stopped/paused biologic therapy.
Within the 24-week study period, 7.9% (n=13) required steroids, 2.4% (n=4) had an IBD-related hospital admission and 8.5% (n=14) experienced an adverse reaction of which 7 were injection site-related. One patient experienced an anaphylactoid reaction upon restarting IV vedolizumab.
There were no statistically significant associations between baseline characteristics (including clinical or biochemical markers, duration of vedolizumab use or prior ant-TNF exposure) and week 32 outcomes.

Conclusion
Switching from IV to SC vedolizumab appears to maintain rates of remission with no significant changes in biochemical markers, clinical scores or quality of life, with SC administration persistence of 86% at week 24. Further long-term data on safety is required.