bluuebunny/crossref_metadata_2025_split huggingface dataset:
P279 Potential of managed care programmes for patients with inflammatory bowel diseases – results from a large survey study among physicians and IBD-patients in Germany, Austria and Switzerland (the EASEIBD study)
Authors: Bokemeyer B , Kaiser C , Primas C , Novacek G , Biedermann L , Seibold F , Tappe U , Bettenworth D , Graw J , Hartmann P , Plachta-Danielzik S , Schultz C 
Published: May 2021

Abstract

Background
IBD-care may be challenging and benefits from a multidisciplinary, cross-sectoral treatment approach and active patient involvement. However, occasionally there is a lack of patients′ empowerment and additionally, a necessity for the optimisation of physicians′ treatment is apparent. Furthermore, there is a deficiency in evidence regarding the effectiveness of structured care approaches (“managed care”) on patient-related outcomes (PROs). Therefore, our study aims to evaluate the potential of managed care programmes for IBD patients.

Methods
EASEIBD is a cross-border study conducted by IBD-DACH, an IBD working group in Germany (D), Austria (A) and Switzerland (Ch). Within the DACH-region, a cross-sectional survey of patients and physicians from IBD hospital-outpatient departments and gastroenterology practices was carried out. The questionnaire evaluated the effect of instruments and contextual factors of IBD-care with regard to quality of life (QoL). Additionally, the effects of “managed care” instruments were examined while considering centre-related structural characteristics. The analysis was performed using a multivariate multilevel regression model, controlled by various physician and patient characteristics.

Results
2536 IBD-patients from 66 centres (643 IBD-patients/quarter; 31% hospital out-patient departments) were consecutively enrolled in EASEIBD (centres/IBD-pat.: D-52/1735; A-10/647; Ch-4/154). Overall, patient satisfaction (77-84%) (Fig. 1) as well as perceived quality of care (82-87%) (Fig. 2) was high and comparable in the descriptive analysis between German, Austrian and Swiss IBD-patients. Statistically significant differences were only found in single characteristics, e.g. in quality of life (EQ5D-VAS) (p=0.004) (Fig. 3). However, these do not appear clinically relevant with regard to the absolute values. In the entire DACH-region there were detectable effects of elements representing structural quality and assessments of the centres, with regard to the perceived quality of patient care (Fig. 4), whereby, in particular, a positive influence of web-based instruments (e.g. homepage) (p=0.040) and potential use of homecare calprotectin (0.046) had the most pronounced effect. Noteworthy, in Germany, the implementation of specialised IBD nurses was associated with a beneficial impact on patients′ QoL (0.027) when compared to the cumulative results from the entire DACH region (p=0.681).

Conclusion
Our study shows that the use of elements of managed care programmes resulted in a high process quality, which is evident from the reported high patient satisfaction and quality of care by IBD-patients in the entire DACH region, and qualifies this area as a suitable common study landscape.
P332 Population pharmacokinetics of ozanimod and active metabolite CC112273 in patients with ulcerative colitis
Authors: Shen J , Tatosian D , Sid-Otmane L , Teuscher N , Chen L , Zhang P , Tirucherai G S , Chitakara D , Marta C 
Published: May 2021

Abstract

Background
Ozanimod is an oral small molecule sphingosine 1-phosphate receptor modulator approved for relapsing forms of multiple sclerosis (RMS) and under development for ulcerative colitis (UC) and Crohn’s disease (CD). Following multiple dosing of ozanimod in healthy subjects, ozanimod and two of the active metabolites CC112273 and CC1084037 represent approximately 6%, 73%, and 15% of circulating total active drug exposure, respectively. Two separate pharmacokinetic (PK) models were developed for the most prominent metabolite CC112273 and ozanimod. CC1084037 was not modeled due to the high correlation between CC112273 and CC1084037 plasma concentrations. Therefore, this analysis aims to characterise the PK of ozanimod and the major metabolite CC112273 in UC and RMS population.

Methods
Subjects from 11 studies (Phase 1 to Phase 3) in healthy volunteers, RMS, and UC patients were included in this population PK analysis. The analyses included a total of 18901 concentrations from 2890 subjects for CC112273 and 18834 PK concentrations from 2977 subjects for ozanimod.
A 2-compartment model was used to describe the concentration-time profiles of both ozanimod and CC112273, separately. The influence of weight, age, sex, race, disease, or smoking status and hepatic function on the PK of ozanimod and CC112273 were explored. The impact of concomitant corticosteroids on CC112273 PK were evaluated post hoc.

Results
While the overall apparent clearance of ozanimod was 7% lower in RMS patients compared to UC, similar exposures were observed in both populations. The most influential covariate on ozanimod PK was body weight, with a modest 23% increase in apparent clearance for a 102-kg subject relative to a 70-kg subject (Figure 1).
The apparent clearance of CC112273 was 16% greater in RMS patients compared to UC patients, resulting in a slightly higher exposure for UC patients. Increasing body weight had a modest reduction in clearance, while smoking had the largest influence on CC112273 PK of approximately 108% increased clearance (Figure 2). Post-hoc results showed no impact of concomitant prednisone or prednisolone on the PK of CC112273.
Other factors, including age, race, sex, or hepatic impairment did not impact the PK of ozanimod or CC112273 PK.

Conclusion
The population PK model of CC112273 indicates that covariates with the largest effect on CC112273 PK parameters were body weight and smoking status. However, no covariate impacted clearance by more than 25%. The PK of ozanimod and CC112273 were not meaningfully impacted by age including in the elderly, body weight, race, sex, hepatic function, or concomitant prednisone or prednisolone. Overall, the PK of ozanimod and CC112273 were comparable in UC and RMS patients.
P424 Treatment persistence of first-line anti-TNF therapy in patients with inflammatory bowel diseases: results from a real-world study over 20 years
Authors: Blesl A , Binder L , Högenauer C , Wenzl H , Borenich A , Pregartner G , Berghold A , Mestel S , Kump P , Baumann-Durchschein F , Petritsch W 
Published: May 2021

Abstract

Background
Anti-TNF therapy is still the most frequently used first-line biologic treatment in inflammatory bowel disease (IBD). This study aimed to determine length of treatment persistence and to describe reasons for discontinuation of first-line anti-TNF therapy used in the standard care of IBD patients.

Methods
A single-center, real-world, retrospective study including IBD patients (Crohn’s disease (CD), ulcerative colitis (UC), IBD unclassified (IBD-U)), who received an anti-TNF therapy in the last 20 years at the study center, was conducted. Length of first-line anti-TNF therapy, differences in treatment duration between infliximab (IFX) and adalimumab (ADA) and between CD and UC, reasons for discontinuation, side effects leading to cessation, treatment following first-line anti-TNF therapy, rates of surgery and death, and factors being associated with treatment failure were assessed.

Results
586 patients were identified as having received first-line anti-TNF therapy at the study center. 48 patients were excluded due to shortness of available data. 538 patients (CD: 367, UC: 147, IBD-U: 24) with a median follow-up of 8.1 years were included in the analysis. Median (IQR) treatment persistence was 21.0 (6.0, 57.0) months in the total cohort. Treatment withdrawal arose frequently (40%) within the first year of therapy and treatment persistence was longer in CD compared to UC (CD: 27.0 (8.0, 71.0) months, UC: 11.0 (3.0, 34) months, p&lt;0.001). Treatment failure (51%) and side effects (24%) were the most commonly noticed reasons for withdrawal from therapy. 14% withdrew from therapy due to remission. The diagnosis of UC, female sex, the absence of prior intestinal resections, lower hemoglobin and albumin levels at anti-TNF initiation predicted treatment failure. Patients with CD continued ADA treatment longer than IFX treatment (ADA: (40.5 (14.2, 80.5) months, IFX: 18.0 (4.8, 65.0) months, p&lt;0.001). Within the follow-up period, 17% of UC patients underwent colectomy and 34% of CD patients had at least one intestinal resection after start of first-line anti-TNF therapy. 2% of all patients died due to various reasons.

Conclusion
Treatment persistence of first-line anti-TNF therapy is limited in IBD patients due to a large proportion of treatment failures and side effects.
P508 Dose adjustment in patients with moderate to severe ulcerative colitis: results from year 3 of the UNIFI maintenance study long-term extension
Authors: Rowbotham D S , Scherl E J , Sands B E , Panaccione R , Peyrin-Biroulet L , Zhang H , Miao Y , Leong R W , Afif W , Arasaradnam R P , Danese S , Marano C 
Published: May 2021

Abstract

Background
The UNIFI randomized-withdrawal maintenance study and long-term extension (LTE) evaluated the safety and efficacy of subcutaneous (SC) ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) who had responded to intravenous (IV) UST during induction. We evaluated the efficacy of UST dose adjustment through Week (Wk) 152 of the long-term extension (LTE).

Methods
523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 weeks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST patients who completed wk44 entered the LTE. PBO patients were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, patients in the LTE were eligible to receive dose adjustment starting at Wk 56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Patients in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Patients were assessed for symptomatic remission, partial Mayo scores, and inflammatory markers ≥16 wks after dose adjustment.

Results
Overall, 60 patients (42.6%) in the q12w group and 40 patients (28.0%) in the q8w group underwent dose adjustment (or sham dose adjustment) prior to Wk 156 of the LTE; 51 and 39 patients in each group, respectively, had dose adjustment at Wk 136 or before, providing≥16 wks of data after dose adjustment (Table). At the first visit ≥16 weeks after dose adjustment, 70.6% of patients who adjusted from q12w to q8w and 61.5% who sham dose adjusted from q8w to q8w were in symptomatic remission. At the time of dose adjustment, 27/51 patients (52.9%) in the q12w group and 25/39 patients (64.1%) in the q8w group were in symptomatic remission. Of those who were in symptomatic remission at the time of dose adjustment, the majority (81.5% and 68.0%, respectively) were maintained in symptomatic remission at the first visit ≥16 wks after dose adjustment. Of those who were not in symptomatic remission at the time of dose adjustment, 58.3% and 50.0%, respectively, were in symptomatic remission at the first visit ≥16 wks after dose adjustment. Mean partial Mayo scores and CRP levels decreased after dose adjustment (Table).

Conclusion
Patients may benefit from UST dose adjustment to q8w.
P522 Effectiveness of tofacitinib in a real-world Israeli cohort of patients with moderate-severe ulcerative colitis
Authors: Avni Biron I , Bar-Gil Shitrit A , Koslowsky B , Kopylov U , Levartovsky A , Weisshof R , Aviv-Cohen N , Maharshak N , Hovel D , Naftali T , Goren I , Snir I , Ollech J , Banai H , Lena B , Dotan I , Yanai H 
Published: May 2021

Abstract

Background
We sought to define the effectiveness of tofacitinib in a real-world (RW) cohort of patients with moderate to severe ulcerative colitis (UC).

Methods
This was a multi-center retrospective observational cohort study (2017–2020). Clinical response and remission were defined as a reduction in Simple Clinical Colitis Activity Index (SCCAI) or partial Mayo score (PMS) of ≥3, and SCCAI ≤2 or a PMS ≤1, respectively.

Results
We included 73 patients (47% male; median age 26 years [IQR 19.5–39.5], disease duration 7 years [IQR 2.5–14.5], follow-up 7.1 months [IQR 3–12]), 91% biologics-experienced, and 74% ≥ 2-biologics. Half of patients used concomitant steroids. Overall, 56.1% discontinued therapy due to either lack of response and/or adverse events (AEs), median time to discontinuation - 9.7 months (IQR 3.4–16). Based on per-protocol analysis, after induction (week-8–16), 33.3% achieved response, 23.3% remission, and 19% corticosteroid free remission. At early maintenance (week 26), 50% achieved response, 26.8% remission, and 24.4% corticosteroid free remission. There were no differences between biologics-experienced and naïve patients. Seventeen patients (23.2%) had an AE: herpes zoster- 2.7%, hospitalization- 12.3%, and colectomy- 2.7%. Remitters had higher albumin level compared with non-remitters (4.2±0.35 Vs. 3.8±0.35, P=0.023, respectively).

Conclusion
In this multicenter RW cohort of highly biologics - experienced patients with UC, those who continued tofacitinib throughout induction achieved 50% response and 27% remission. Tofacitinib was well-tolerated.
P559 Efficacy of Ustekinumab in the treatment of patients with Crohn’s disease with failure to previous conventional or biologic therapy: an observational real-life study
Authors: Miranda A , Cuomo A , Camera S , Ciacci C , De Filippo F R , Gravina A G , D’Onofrio V , Melina R , Manguso F , Priadko K , Facchiano A , Bennato R , D’Onofrio R , Cuomo R , Mucherino C , Romano M 
Published: May 2021

Abstract

Background
Ustekinumab (UST), a human anti-IL12/23p40 monoclonal antibody, was approved by FDA and EMA for the treatment of moderate to severe Crohn’s disease (CD). Whether UST is effective in inducing deep remission, including mucosal healing and transmural healing, in patients with CD in a real life setting is not completely clear.

Methods
The study was performed on 92 subjects (47 males; 45 females; mean age: 42 (17–78) from six medical centers in Campania, Italy, with confirmed diagnosis of moderate to severe Crohn’s disease and no neoplasia. In all patients diagnosis of CD had been reached to years earlier. Before inclusion, all patients had been exposed and had failed to respond to conventional and/or at least one biological therapy.The administration of UST was as follows: IV infusion at week 0 (3 vials of 130 mg each if body weight of 55–85 kg; 2 vials of130 mg each if body weight &lt; 55 kg) and subsequent SC injections (90 mg) q8w thereafter. At enrollment, all subjects underwent colonoscopy and were divided into groups according to endoscopic evaluation: 5 (5.4%) patients had erosions; 24 (26.1%) inflammation; 63 (68.5%) ulcers. Based on the CDAI value, 52 (56.5%) patients had a CDAI of 180–220, 35 (38%) had a CDAI of 220–450, and 5 (5.4%) had a CDAI &gt;450.
All patients underwent endoscopic examination and bowel MRI or ultrasonography at baseline and at week 52 to evaluate mucosal and transmural healing. Clinical response was defined as a reduction of CDAI by at least 100 points; clinical remission when CDAI was lower than 150. Clinical response and remission were evaluated at baseline and on 5 different occasions throughout a 12 months follow-up. Incidence of treatment-related adverse events (TRAEs) was recorded during the study period.

Results
Seventeen patients interrupted therapy while 75 patients continued follow-up until the fifth visit. Clinical response at week 52 was achieved in 38 (50,5%) patients and clinical remission in 29 (39%). Twenty-six (34%) patients showed mucosal healing, 34 (45%) showed partial endoscopic response. Fifteen patients (20%) did not show any change during endoscopic evaluation at follow-up. All patients showing mucosal healing also showed transmural healing, as assessed by ultrasonography or MRI. No major TRAEs were observed during treatment.

Conclusion
In this multi-center, real life study, we show that UST was well tolerated and effective in inducing clinical response and clinical remission in patients with moderate to severe CD who had previously failed to respond to conventional or biologic therapy. UST showed limited efficacy in inducing deep remission (i.e. mucosal+transmural healing).
P560 Clinical outcomes of vedolizumab maintenance treatment for Korean patients with inflammatory bowel disease who failed anti-TNF therapy: A KASID prospective multicenter cohort study
Authors: Oh K , Kim J , Kim N , Yoon H , Lee K M , Park D I , Choi C H , Lee C K , Eun C S , Kang S B , Kim E S , Kim Y S , Jung S A , Jung Y , Kim T O , Park S J , Im J P , Seo G S , Ye B D 
Published: May 2021

Abstract

Background
We investigated the real-life effectiveness and safety of vedolizumab maintenance treatment among Korean patients with Crohn’s disease (CD) or ulcerative colitis (UC) who previously failed anti-tumour necrosis factor (anti-TNF) therapy.

Methods
Adult patients with CD or UC who have previously failed anti-TNF therapy and received vedolizumab were prospectively enrolled from 16 hospitals in Korea. The primary outcome was clinical remission at week 54. Clinical remission was defined as a Crohn’s disease activity index (CDAI) &lt;150 and a partial Mayo score ≤2 with a combined rectal bleeding and stool frequency subscore ≤1. We also analyzed factors associated with clinical remission at week 54.

Results
Between August 2017 to July 2020, a total of 165 patients (81 with CD and 84 with UC) received vedolizumab therapy, of whom 154 patients (93.3%) (75 with CD and 79 with UC) received vedolizumab maintenance therapy (Table 1). Clinical remission and response rates at week 54 were 22.2% and 24.1% among patients with CD and 41.4% and 45.7% among patients with UC, respectively (Figure 1A and 1B). Among 70 patients with UC with baseline Mayo endoscopic subscore ≥2, endoscopic remission (Mayo endoscopic subscore ≤1) at week 54 was observed in 19 patients (27.1%). Out of 50 patients with CD with ulcers in baseline endoscopy, 2 patients (4%) showed a disappearance of ulcers at week 54 (Figure 1C). In the multivariable analysis, age at baseline (adjusted odds ration [aOR] 1.065, 95% confidence interval [CI] 1.003–1.131, P=0.041) and Mayo endoscopic subscore at baseline (aOR 0.141, 95% CI 0.026–0.746, P=0.021) were significantly associated with clinical remission at week 54 among patients with UC (Table 2). No factors were found to be associated with clinical remission at week 54 among patients with CD. Among patients who experienced one or more adverse events (n=134, 81.2%), serious adverse events occurred in 82 patients (49.7%) (Table 3). Disease exacerbation was the most common adverse events (n=89, 53.9%).

Conclusion
The real-life effectiveness of vedolizumab maintenance treatment for Korean patients with UC who failed anti-TNF therapy was generally similar with the outcomes reported from the previous Western studies. A substantial proportion of patients with CD experienced a loss of response during the first year of treatment. Less severe disease at baseline was associated with clinical remission at 1 year of vedolizumab therapy among patients with UC.
P611 Incidence, clinical presentation, and severity of SARS-CoV-2 infection in IBD patients in the second and the third wave of infection
Authors: Algaba Garcia A , Guerra I , Castro S , Jiménez L , Garza D , Aller M D M , Granja A , Guardiola A , Bellart M , Pizarro N , Bermejo F 
Published: May 2021

Abstract

Background
Data about the SARS-CoV-2 infection in inflammatory bowel disease patients (IBD) are scarce. Our aim was to analyse the incidence, clinical presentation, and severity of SARS-CoV-2 infection in IBD patients in the second and the third wave of infection.

Methods
Cross-sectional, observational study in IBD patients with confirmed SARS-CoV-2 infection by RCP and/or antigen tests from 01 July 2020 to 01 March 2021. All data were collected by telephone interview and reviewing the electronical medical records.

Results
Fifty-one of 805 IBD patients followed in our Unit were diagnosed of SARS-CoV-2 infection in this period (6.3%; 95% CI 4.6–8.0). Mean age: 45±13 years old; 56.9% female, 23.5% smokers, 56.9% Crohn’s disease, 29.4% comorbidities and 17.6% asymptomatic. Digestive symptoms were reported in 22 patients (43.1%), with diarrhoea as the most common (39.2%, median duration: 4 days; IQR 1–7). The most frequent symptoms other than diarrhoea were low-grade fever/fever in 43.1% (median duration: 3 days; IQR 1–6.5) and dysosmia/dysgeusia in 39.2% (median duration: 15 days; IQR 7–30). Only one patient (2%) was diagnosed with IBD flare-up during infection. Six patients (11.8%) temporarily withdrew their IBD treatment because of COVID-19. Most of the patients had a mild disease (88.2%), no patient had to be admitted in the intensive care unit. Only one patient died (2%) due to SARS-CoV-2 infection and multiple previous comorbidities, 52 years old male with ulcerative colitis in treatment with Mesalazine and dendritic cell sarcoma, common variable inmunodefiency, and primary sclerosing cholangitis progressing to cirrhosis. In the multivariate analysis, the presence of dyspnoea was associated with more severe infection (p=0.007; OR:25.7; 95% CI 2.4–277.8). Patients on immunomodulators and/or biological therapy did not have more severe disease compared to non-immunosuppressed patients (p&gt;0.05).

Conclusion
SARS-CoV-2 infection was relatively frequent is our series. Dyspnoea was associated with a more severe infection. Severity of SARS-CoV-2 infection was not related to immunosuppression or development of IBD flare-ups and only a small percentage of patients needed to modify IBD medication during infection