bluuebunny/crossref_metadata_2025_split huggingface dataset:
P281 Evaluation of trough level and disease activity after switch from adalimumab originator to biosimilar in patients with Inflammatory Bowel Disease
Authors: Deprez N , De Somer T , Baert D , Deceuninck M , Huys I , Mattens V , Sterckx A , Vanden Branden S , Vanderstraeten E , Vandervoort J , Vanheddegem N , Dewint P 
Published: May 2021

Abstract

Background
SB5 is approved as a biosimilar to the adalimumab (ADA) originator. Bio- and efficacy equivalence, as well as comparable safety and immunogenicity have been demonstrated in Phase I and III randomised clinical trials. In this study we want to describe the trough levels and effectiveness of switch to a biosimilar in a real-life Inflammatory Bowel Disease (IBD) population.

Methods
In 2 Belgian IBD centres, patients in clinical remission or stable response and treated with ADA originator were offered to enter a phase IV, interventional trial of switch to biosimilar SB5. Assessments were done at baseline, at 8 weeks, 6 and 12 months post-switch. Therapy type and dosing regimen remained unchanged the first 8 weeks; after week 8, dose adjustments could be made based on trough level and/or at the discretion of the treating physician. Trough serum ADA concentrations were measured by enzyme-linked immunosorbent assay (ELISA). The primary outcome measurement was the description of ADA trough level over time after the switch. The secondary outcome measurements were secondary loss of response (SLOR) (defined at physician’s discretion), disease activity scores and biochemical assessments (faecal calprotectin (fCal), leukocyte count (LC) and C-reactive protein (CRP)).

Results
In the study, 110 patients were enrolled from whom 84 had Crohn’s disease and 26 had ulcerative colitis. By 12 months, SB5 was stopped in 5 patients because of high ADA antidrug antibodies at both baseline and at week 8. Nine patients presented with SLOR of whom 3 discontinued treatment with SB5, the remaining 6 patients received treatment optimisation. Table 1 displays the core results concerning the ADA trough levels over time. Table 2a and 2b display disease activity scores and biochemical parameters at the different time points.

Conclusion
In this pragmatic, interventional phase IV trial, ADA trough levels remain within the therapeutic range after switch from originator to SB5. The proportion of patients in our study with SLOR is in line with what is described in literature. In patients persisting on SB5, no change in disease activity over time is observed, based on both disease activity scores and biochemical parameters.
P288 Vedolizumab May Be An Effective Option For The Management Of Postoperative Recurrence Of Crohn’s Disease
Authors: Macaluso F S , Cappello M , Crispino F , Grova M , Privitera A C , Piccillo G , Magnano A , Ferracane C , Belluardo N , Giangreco E , Fries W , Viola A , Di Mitri R , Mocciaro F , Camilleri S , Garufi S , Renna S , Casà A , Maida M , Orlando A 
Published: May 2021

Abstract

Background
The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn’s disease (CD) following ileocolonic resection is currently unknown.
We aimed to assess the effectiveness of VDZ in this setting.

Methods
All consecutive CD patients with an available baseline colonoscopy at 6-12 months from the ileocolonic resection and treated with VDZ for the postoperative recurrence after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ. In patients with Rutgeerts score i0 or i1 at baseline, endoscopic success was defined by maintenance of Rutgeerts score i0 or i1; in patients with Rutgeerts score ≥ i2 at baseline, it was defined as reduction of at least one point of Rutgeerts score. The secondary outcome was clinical failure, assessed at one year and at the end of follow-up.

Results
Seventy patients were included (median follow-up: 23.5 months). All 9 patients without endoscopic recurrence at baseline (Rutgeerts score i0 or i1) and available post-treatment colonoscopy maintained a Rutgeerts score i0 or i1 (treatment success: 100%). In patients with endoscopic recurrence (Rutgeerts score ≥ i2 at baseline), a reduction of at least one point in the Rutgeerts score was obtained in 20 out of 42 patients (47.6%). By combining the two subgroups, the overall endoscopic success was achieved in 29 out of 51 patients (56.9%). Furthermore, 14 out of 42 patients (33.3%) with endoscopic recurrence at baseline achieved a Rutgeerts score i0 or i1 at the subsequent colonoscopy. Clinical failure was reported in 13/70 patients (18.6%) at one year, and in 23/70 patients (32.9%) at the end of follow-up. A new resection was required in 7/70 patients (10.0%).

Conclusion
VDZ may be a therapeutic option for the management of postoperative recurrence of CD. Further studies are needed to confirm these results.
P292 Effect of drug therapy on the lipid profiles of patient with Inflammatory Bowel Disease: a systematic review and meta-analysis
Authors: Sleutjes J A M , Roeters van Lennep J E , Boersma E , de Vries A C , van der Woude C J 
Published: May 2021

Abstract

Background
Increases of lipid levels associated with inflammatory bowel disease (IBD) medication have been previously reported. However, it is unknown whether this effect is similar for all IBD drug classes.

Methods
We performed a systematic literature search of randomized controlled trials and observational cohort studies of IBD treatment with corticosteroids, anti TNFα agents and tofacitinib that assessed total cholesterol (TC) before and after short-term (≤8 week) and long-term (≥12 week) treatment. Data of 11 studies (1,663 IBD patients) were pooled using a random effect model with as primary outcome TC levels. Lipid changes were reported as mean difference on the log2-scale (MDlog2) with 95% CI. The effect of patient and disease characteristics on TC changes were analyzed in 6 studies with individual patient data of 1,211 patients.

Results
A significant increase in TC was observed after treatment with corticosteroids, anti TNFα agents and tofacitinib (short-term +0.370, +0.197 and +0.190; long-term: +0.452, +0.068 and +0.162, respectively). (Figure 1) After correcting for age, sex, BMI and CRP, increases of TC levels after start of corticosteroids and tofacitinib treatment were higher (short-term: +0.293 and +0.161; long-term: +0.090 and +0.127, respectively) as compared to anti TNFα agents (short-term: -0.059, long-term: +0.041). (Figure 2)

Conclusion
Changes in lipid levels differ between IBD drug classes. TC levels increase was strongest for corticosteroids followed by tofacitinib but not observed for anti TNFα agents. Whether TC change associated with IBD treatment has effect on CVD risk requires further study.
P307 Modelling of the relationship between ustekinumab exposure, faecal calprotectin and endoscopic outcomes in patients with Crohn’s disease
Authors: Wang Z , Verstockt B , Vermeire S , Sabino J , Ferrante M , Declerck P , Dreesen E 
Published: May 2021

Abstract

Background
In the UNITI endoscopy sub-study, only 17.4% of patients with Crohn’s disease (CD) on ustekinumab achieved endoscopic response and 10.9% achieved endoscopic remission at week (w)44. We aimed to investigate if improved endoscopic outcomes can be achieved through dose optimisation based on a population pharmacokinetic-pharmacodynamic (popPK-PD) modelling and simulation analysis.

Methods
Real-world data were obtained from 83 patients with moderate-to-severe CD (94% multi-refractory) enrolled in a prospective cohort study receiving ustekinumab 6 mg/kg induction and every eight-week (q8w) 90 mg maintenance therapy. Ustekinumab serum concentrations were measured at mid-dose (w4) and trough (w8, w16, w24). Faecal calprotectin (fCal) was measured at baseline and at w4, w8, w16, w24. Endoscopic response (≥50% decrease in simple endoscopic score for CD [SES-CD]) and endoscopic remission (SES-CD ≤2) were assessed at w24. Modelling and simulation were performed using NONMEM 7.4.

Results
Three sequential models were developed: a two-compartment popPK model linking ustekinumab dose to ustekinumab exposure, an indirect response popPK-PD model describing the effect of ustekinumab exposure on fCal, and a logistic regression popPD model linking fCal at w8 to endoscopic outcomes at w24 (Figure 1). Ustekinumab clearance increased with decreasing serum albumin and increasing bodyweight. The terminal half-life of ustekinumab in a median patient (bodyweight 65 kg, serum albumin 42.7 g/L) was 20.4 days. fCal decreased with increasing ustekinumab exposure. The probability of endoscopic response at w24 increased from 10.0% to 17.9% with fCal at w8 decreasing from 1,800 μg/g to 694 μg/g (Figure 2a) The probability of endoscopic remission at w24 increased from 2.1% to 10.0% with fCal at w8 decreasing from 1,800 μg/g to 214 μg/g (Figure 2b).The results from the simulation-based comparison of q8w and q4w maintenance dosing are shown in Table 1. Dose doubling (180 mg q8w), as opposed to interval halving (90 mg q4w), was predicted to result in a ustekinumab trough concentration of 2.4 μg/mL instead of 4.8 μg/mL.

Conclusion
The developed model can guide clinical trial design and support model-informed dose optimisation to improve endoscopic outcome rates. Although our analyses showed that q4w dosing resulted in higher ustekinumab and lower fCal concentrations, the proportion of patients achieving endoscopic remission was limited.
P308 Effectiveness and Safety of tofacitinib for the Treatment of Ulcerative Colitis: A Single-Arm Meta-analysis of Observational Studies
Authors: Macaluso F S , Maida M , Ventimiglia M , Orlando A 
Published: May 2021

Abstract

Background
Several observational studies on Tofacitinib (TOFA) for the treatment of ulcerative colitis (UC) have been published over the last 2 years. The aim of this single-arm meta-analysis was to estimate the effectiveness and safety of TOFA arising from real-world observational studies.

Methods
PubMed Central/Medline and Embase, as well as reference lists of articles, were systematically searched for real-world observational studies of TOFA for the treatment of UC through November 2020.

Results
Seven studies comprising 759 patients met the inclusion criteria. Almost all patients (range: 76.5-100%) had been previously exposed to anti-TNFs, and a variable proportion (range: 38.8-100%) had been previously treated with Vedolizumab The pooled estimate rates were 49% for clinical response, 40% for clinical remission, and 34% for corticosteroid-free clinical remission at induction, while the rates of endoscopic response and endoscopic remission were 37% and 19%, respectively. At maintenance, the pooled estimate rates of clinical response, clinical remission, and corticosteroid-free clinical remission were 36%, 35%, and 24%, respectively. The pooled estimate of incidence rate of total adverse events was 53.0 per 100 person-years (PY), while the pooled estimate of incidence rate of withdrawal of TOFA due to adverse events was 9.3 per 100 PY, with a pooled rate of infections of 17.6 per 100 PY.

Conclusion
Cumulative analysis of data from real-world studies confirmed the good efficacy of TOFA in UC shown by randomized controlled trials for both induction and maintenance, while the safety profile was consistent with previous reports.
P317 Societal cost-of-illness of Inflammatory Bowel Disease has rapidly increased over the years and differs between continents: A systematic review
Authors: Van Linschoten R , Visser E , Niehot C , van der Woude J , Hazelzet J , van Noord D , West R 
Published: May 2021

Abstract

Background
With increasing incidence of Inflammatory Bowel Disease (IBD) in developing countries and increasing prescription rates for biologics globally, knowledge on the cost burden of IBD and cost drivers is essential for health policy makers worldwide. We conducted a systematic review to determine cost-of-illness of IBD and assess time trends and geographical differences.

Methods
A systematic review of population-based studies that estimated cost-of-illness of IBD and were published in Embase, Medline, Web of Science and Google Scholar. Studies on interventions and those reporting costs for a subset of patients defined by phenotype or treatment were excluded, as these do not give a representative estimate of the cost-of-illness of IBD. Only studies published in English were included. Methodology of all included studies was assessed and costs were adjusted to 2018 US dollars.

Results
In total, 4,837 unique studies were screened on title and abstract and 4,730 excluded. After full-text screening, 64 of the remaining 107 studies were included in the systematic review. The study methodologies differed considerably, with large differences in perspective, valuation method and source population. Mean annual healthcare costs for prevalent Crohn′s disease (CD) cases in the last 10 years were in Asia $4,463; Europe $12,396 and North America $17,508. Costs for prevalent ulcerative colitis (UC) patients in the same period were $1,654, $7,206 and $13,569 respectively. For CD, the cost drivers moved from inpatient (61% of total costs) in 1995 to medication costs (77%) in 2016. Similar trends were identified for UC (1998: 50% and 36% versus 2016: 9%, and 82% for inpatient and medication costs, respectively). This cost trend is primarily attributable to an increase in medication costs in all four geographical areas, while in- and outpatient costs were relatively stable during the same time period. The annual costs of absenteeism and presenteeism per prevalent case of CD were $5,638 in Asia and $6,485 in Europe. For UC these costs were $4,828 and $6,414 respectively. Annual costs of absenteeism and presenteeism in North America were $20,074 per patient for a combined cohort of UC and CD patients.

Conclusion
Per patient costs for IBD are increasing worldwide, with highest costs in North America and lowest in Asia. This is primarily due to an increase in medication costs. Productivity costs are substantial and might even exceed healthcare costs. Biologic therapy was expected to decrease inpatient costs by reducing hospitalisations and surgery, but this does not appear to be the case. Continuing growth of these costs can lead to an intolerable burden on healthcare systems worldwide.
P320 Combined mesenchymal stromal cells and anti-cytokine therapy of perianal Crohn’s disease
Authors: Knyazev O , Kagramanova A V , Lishchinskaya A , Shkurko T , Li I , Parfenov A 
Published: May 2021

Abstract

Background
Perianal fistulas are common types of fistulas in Crohn’s disease (CD). Mesenchymal stromal cells (MSC), which have immunomodulatory properties and high regenerative potential, are currently also used for the treatment of fistula CD.
The purpose of this study was to compare the effectiveness of combined therapy (local and systemic) mesenchymal stromal cells (MSC) of bone marrow, in the effectiveness of combination therapy MSC (local administration) and infliximab (IFX), as therapy the IFX with immunomodulators on the healing of simple perianal fistulas in Crohn’s disease (CD).

Methods
Seventy-five patients with CD with perianal lesions were divided into three groups depending on the method of therapy. The first group of СD patients aged 19 to 59 years (Me-29) (n=25) received a culture of MSC systematically according to the scheme and locally. The second group of patients with CD (n=25) aged 20 to 60 years (Me-28) received anti-cytokine therapy with IFX and immunomodulators. The third group of patients with CD (n=25) aged 20 to 62 years (Me-30) received MSC systemically and locally, as well as anti-cytokine therapy with IFX. The dynamics evaluated the complete closure of the external opening of the fistula. Ano-and rectosigmoscopy was performed 2 and 12 months after the start of therapy. The comparative analysis was performed using four-field tables using nonparametric statistical criteria.

Results
After 2 months in the first group of patients, healing of simple fistulas was observed in 15/25 (60.0%), in the third group-22/25 patients (88.0%) (RR–1.467; 95% CI - 1.032-2.084; x2= 3.742; p=0.02948).
After 2 months in the second group, healing of simple fistulas was observed in 16/25 (64.0%) (RR-1.37; 95% CI 0.991-1.908; x2=4.091; p=0.056).
After 12 months in the first group of patients, healing of simple fistulas was observed in 17/25 (68.0%), in the third group-24/25 (96.0%) patients (RR 1.412; 95% CI 1.066–1.869; x2=7.399; p=0.0124).
After 12 months in the second group, healing of simple fistulas occurred in 18/25 (72.0%) (RR -0.750; 95% CI 0.580– 0.970; x2=5.922; p=0.0488).

Conclusion
Combined cells and anti-cytokine therapy of CD with perianal lesions contributes to more frequent and prolonged closure of simple fistulas, compared with MSC monotherapy and IFX monotherapy.
P348 Perception of cancer risk in inflammatory bowel disease-associated dysplasia and management practice is influenced by colonoscopy experience and workplace affiliation: results of an international clinician survey
Authors: Kabir M , Thomas-Gibson S , Hart A , Wilson A 
Published: May 2021

Abstract

Background
A successful inflammatory bowel disease (IBD) surveillance cancer preventative programme requires effective action to be taken when dysplasia is detected. This is the first international cross-sectional study to evaluate current clinician understanding of IBD dysplasia risk, their management practice and adherence to the most recent international guidelines introduced since 2015.

Methods
A 15-item online survey was disseminated to IBD gastroenterologist and colorectal surgeon members of the British Society of Gastroenterology in June 2019 and the European Crohn’s and Colitis Organisation in February 2020.

Results
294 clinicians (93.5% gastroenterologists) from 60 countries responded. A significant proportion indicated not having access to high definition chromoendoscopy IBD surveillance (23%) in their endoscopy units. University hospitals were more likely than non-academic workplaces to provide second expert histopathologist review (67% vs. 46%; p=0.002) and formal multidisciplinary team meeting discussion (73% vs. 52%; p=0.001) of dysplasia cases. Most respondents would advocate endoscopic resection of all visible dysplasia and would refer to a regional specialist therapeutic endoscopist if needed (70%). However, perceptions of 5-year cancer risk associated with endoscopically unresectable low-grade dysplasia (LGD) varied between 0 – 100% (median 20% for visible LGD and median 25% for invisible LGD). Although most (98.4%) would advise a colectomy for endoscopically unresectable visible high-grade dysplasia (HGD), only 34.4% would also advise a colectomy for unresectable visible LGD. Working at a non-academic hospital was predictive of a lower perceived cancer risk with HGD [OR 0.4 (95% CI 0.23-0.95)] and unresectable LGD. Working in a private clinic predicted surveillance preference over colectomy to manage invisible LGD [OR 9.4 (95% CI 1.19-74.1)] and multifocal LGD. Greater surveillance colonoscopy experience predicted a lower preference for continued surveillance over colectomy for invisible LGD [OR 0.41 (95% CI 0.20-0.84)].

Conclusion
This study of mainly European gastroenterologists with a sub-specialist interest in IBD has revealed wide variations in colorectal cancer risk perceptions and dysplasia management practices. Clinicians with less IBD surveillance colonoscopy experience and from non-academic centres appeared to have lower cancer risk perceptions and were less likely to advocate colectomy over continued surveillance for high-risk LGD. This study suggests that further education is required to align current management practice with clinical guidelines.
P377 Inadequate response with advanced therapies in real-world patients with Ulcerative Colitis – Results of a German claims database study
Authors: Bokemeyer B , Picker N , Wilke T , Rosin L , Patel H 
Published: May 2021

Abstract

Background
Therapeutic management of Ulcerative Colitis (UC) is challenging, and clinicians are often obliged to attempt a variety of therapies in sequence until an adequate clinical response is achieved. However, real-world data regarding response rates in UC treatment are rare, particularly for later lines of therapy. Thus, this study aimed to investigate the incidence of inadequate response to advanced therapies in patients with UC.

Methods
This retrospective study was based on claims data from a regional German sickness fund covering the period from 01/2014-06/2019. Patients were included if they had at least two outpatient diagnoses in two different quarters or one inpatient diagnosis of UC (ICD-10: K51) and started a newly introduced advanced therapy (adalimumab, golimumab, infliximab, tofacitinib, vedolizumab) in 01/2015-06/2019. Patients were followed from treatment initiation (index date) until the end of the study period or loss to follow-up (median = 23.4 months).
Proxies of inadequate response included: discontinuation (a supply gap of &gt;60 days), switch, escalation (as dose increase exceeding 1.5 times the recommended maintenance dose), augmentation with 5-ASA, corticosteroid (CS) dependency (two CS prescriptions were observed starting more than 14 weeks after the index date), UC-related hospitalization, or UC-related surgery. CS dependency and treatment escalation were only assessed in the maintenance phase. Inadequate response in the analyzed sample was evaluated by means of Kaplan-Meier survival analysis.

Results
Among 574 UC patients (median age: 39 years; female: 53.5%), in whom an advanced therapy was initiated, 458 (79.8%) received an anti-TNF therapy, 113 (19.7%) vedolizumab and 3 (0.5%) tofacitinib. According to the available baseline period, 72 (12.4%) patients were identified as biologic-experienced. Most patients received CS (86.4%) and/or 5-aminosalicylic acids (81.7%) in the 12-month pre-index period. The median time to inadequate response to the initiated advanced therapy was 4.8 months (IQR: 2.6-11.9; Figure 1) with an inadequate response over 12 months in 75% (Figure 2). There was no significant difference in median time to inadequate response between biologic-naïve and biologic-experienced patients (4.9 vs. 4.7 months; p-value = 0.285). During the observable follow-up period, 172 (61%) patients switched from their index agent to another advanced therapy.

Conclusion
From the real-world settings in Germany, we found an inadequate response in UC-patients starting an advanced therapy in 75% of patients over 12 months. There is a need for more effective therapies among these patients.