bluuebunny/crossref_metadata_2025_split huggingface dataset:
P333 Precise and unbiased infliximab dosing in patients with inflammatory bowel diseases using a multi-model averaging approach
Authors: Kantasiripitak W , Outtier A , Thomas D , Kensert A , Wang Z , Sabino J , Wicha S G , Vermeire S , Ferrante M , Dreesen E 
Published: January 2022

Abstract

Background
Underexposure to IFX is a common cause of loss of response in patients with inflammatory bowel disease (IBD). To ensure adequate – but not unnecessarily high – exposure, we aimed to identify a precise and unbiased approach for model-based dosing of IFX in patients with IBD.

Methods
A retrospective study was performed using data from, 54 patients on IFX maintenance therapy. The predictive performance of, 18 published IFX population pharmacokinetic (popPK) models was evaluated using NONMEM (v7.5). A priori prediction (only based on covariates) and Bayesian forecasting (BF; also based on one to three consecutively measured IFX trough concentrations; TC-2, TC-1, and TC0) of the IFX TC+1 was evaluated (Fig, 1). The predictive performance of a single-model approach was compared with two automated multi-model approaches: a model selection algorithm (MSA) and a model averaging algorithm (MAA).1 Relative bias (rBias) and relative root mean square error (rRMSE) were used to determine bias and imprecision of the predicted versus observed TC+1. Clinical acceptability was defined as an rBias between ±20% with a, 95%CI including zero. The predicted and observed TC+1 were classified at, 5.0 mg/L TC target.2

Results
Four models were selected based on their predictive performances and implemented in the TDMx software tool to support model-based IFX dosing in the forthcoming prospective MODIFI study (NCT04982172).
A priori prediction of TC+1 was clinically unacceptable with both single- and multi-model approaches (rBias +30% to +97%, rRMSE, 107% to, 158%; Fig, 2A). Also, a priori prediction had the lowest classification accuracy (median, 59%, IQR, 59%-63%; Fig, 3A). Providing one IFX TC greatly improved predictive performance (rBias -10% to +15%, rRMSE, 30% to, 49%; Fig, 2B, 2C) and classification accuracy (TC-1: median, 70%, IQR, 63%-72%; TC0: median, 80%, IQR, 76%-84 %; Fig, 3B, 3C). More specifically, BF resulted in a significantly lower chance of a falsely predicted ≥5 mg/L TC+1 than a priori prediction (p&lt;0.01). In comparison with BF with TC-1, the availability of TC0 significantly lowered the chance of falsely predicting TC+1 &lt;5 mg/L (unnecessary dose optimisation) (p=0.0034).
Providing more than one previous TC improved predictive performances only marginally (data not shown). In general, MAA performed better than MSA.

Conclusion

Conclusion: A multi-model averaging approach provided more reliable Bayesian forecasts than the single-model approach. Adding one previous trough concentration in addition to covariate information sufficed to provide accurate and unbiased predictions of future exposure. Concentration data collected with a rapid assay may reduce the chance of performing unnecessary dose optimisation.
Reference1. Uster D CPT,2021;2Vande Casteele N Gastroenterology,2017
P347 Sarcopenia is a poor prognostic factor for endoscopic outcomes in patients with Crohn’s disease
Authors: Grova M , Crispino F , Maida M , Vitello A , Tesè L , Rizzuto G , Casà A , Renna S , Macaluso F S , Orlando A 
Published: January 2022

Abstract

Background
Sarcopenia is defined as depletion in lean muscle mass with a loss of muscle strength and has been associated with increased morbidity and mortality in chronic diseases. Despite the risks and potential consequences of low lean muscle mass in patients with Crohn’s disease (CD), the impact of sarcopenia has been poorly evaluated. Therefore, the aim of our study was to assess the role of sarcopenia in predicting clinical and endoscopic outcomes in a cohort of CD patients.

Methods
Consecutive CD patients who started biologics between, 2015 and, 2020 and who underwent abdominal magnetic resonance imaging (MRI) within, 6 months from the beginning of the treatment were enrolled. Sarcopenia was defined as sex-specific total psoas area index (TPAI), measured at the, 3rd lumbar vertebra level, below the, 25th percentile. Multivariate analysis was used to evaluate whether sarcopenia could predict steroid-free clinical remission (Harvey-Bradshaw Index [HBI] &lt;5 and no steroid treatment) and endoscopic response (Simple Endoscopic Score for Crohn’s disease [SES-CD] ≤2 or SES-CD ≤2 and Rutgeerts score i0-i1) after, 52 weeks of treatment.

Results
358 patients were included. Sarcopenic patients were older (p = 0.001), with lower body mass index (BMI) (p = 0.001) and higher Charlson Comorbidity Index (p = 0.02). Furthermore, sarcopenia was associated with a lower rate of endoscopic response (p = 0.014) and a lower SES-CD and Rutgeerts score after, 52 weeks of treatment (p = 0.008; p = 0.001). In multivariate analysis, sarcopenia was an independent predictor of absence of endoscopic response (odds ratio [OR] = 2.8;, 95% confidence interval (95% CI), 1.1–7.5; p = 0.02), along with smoking (OR = 2.39;, 95% CI, 1.05–5.44; p = 0.038) and perianal disease (OR = 2.69;, 95% CI, 1.19–6.08; p = 0.017). Sarcopenia was not associated with steroid-free clinical remission.

Conclusion
This is the first study demonstrating that sarcopenia is a poor prognostic factor for endoscopic response in CD patients. These results suggest that, in the future, screening for sarcopenia on routine abdominal MRI could be used in clinical practice for better management of CD patients in need of biological therapy. Further studies with a larger sample size and a validation cohort are needed to confirm our data.
P364 Comparison of two treatment strategies in IBD: Biosimilar adalimumab (CinnoRA®) in monotherapy and in combination with azathioprine
Authors: AlborziAvanaki F , Moghbel N , Aletaha N , Daryani N E , Farahvash M J , Miroliaii A , Shayegan N , Anjidani N 
Published: January 2022

Abstract

Background
Tumor Necrosis Factor-alpha (TNF-alpha) inhibitors, such as adalimumab (ADA) and infliximab (IFX), are among the most effective biological drugs for inducing and maintaining remission in patients with moderate to severe inflammatory bowel disease (IBD). Previous studies have shown that the effectiveness of IFX is increased with the concomitant use of immunosuppressive drugs. However, little is known about the benefits of adding other immunosuppressive agents to ADA. This study compared the efficacy of monotherapy with biosimilar adalimumab (ADA) and combination therapy with ADA + azathioprine (AZA) in IBD patients.

Methods
In this retrospective cohort study, we evaluated the medical records of anti-TNF-naïve IBD patients referred to Imam Khomeini Hospital in Tehran during, 2019–2020 and were prescribed with biosimilar ADA (CinnoRA®). We compared the effectiveness of treatment, serum levels of ADA, anti-adalimumab antibodies (AAAs), and laboratory data between the two monotherapy and combination therapy groups.

Results
A total of, 65 patients were enrolled in the study. Fifty-six (86.2%) patients had ulcerative colitis (UC), and the remaining had Crohn’s disease (CD). Fifty patients (76.9%) received combination therapy, and, 15 (23.1%) patients were under monotherapy. The rate of clinical remission in the combination therapy group (50%) did not differ significantly from the monotherapy group (40%) (P=0.56). The drug levels were in the therapeutic range (≥7.5 µg/mL) in, 57.5% of patients in the combination therapy group and, 76.9% of those in the monotherapy group (P=0.21). The antibody test result was positive in, 40% of patients taking AZA + ADA and, 10% of patients in the ADA group (P=0.21).

Conclusion
There was no significant difference in the ADA and AAA concentrations between patients receiving ADA monotherapy and combination therapy. Moreover, there was no association between ADA concentrations and the rate of remission in IBD patients. Hence, AZA does not affect the efficacy and pharmacokinetics of ADA in patients with IBD.
P381 Factors predicting risk of colectomy in patients receiving first line steroid and second line biologic salvage therapy for Acute Severe Ulcerative Colitis
Authors: Skinezes Y , Meir Z Y , Abitbol C M , Levartovsky A , Klang E , Kopylov U , Ben-Horin S , Ungar B 
Published: January 2022

Abstract

Background
Acute severe ulcerative colitis (ASUC) is considered a medical emergency and is associated with high rates of colectomy and even death. Intra-venous corticosteroids serve as first line therapy for ASUC. Patients who fail to respond will progress to rescue therapy, comprised of either medical therapy (with Cyclosporine or Infliximab) or colectomy.
We aimed to detect factors predictive of first and second line therapy failure in patients hospitalized for ASUC.

Methods
The Sheba Medical Center database was screened for all hospitalized UC patients between, 2009–2019.
All clinical, demographic and laboratory parameters were retrieved from patients’ medical files.
All parameters were compared between patients either responding to or failing corticosteroids / second line therapy, respectively.
All statistical analyses were performed using the MEDCALC software.

Results
159 hospitalized ASUC patients were identified (117, 73.6% responded to IV corticosteroids;, 42, 26.4% failed first line therapy).
4 (9.5%) of those who failed first line therapy underwent colectomy. The only factor predisposing for corticosteroid therapy failure was pervious biological therapy.
No statistically significant difference was observed in terms of MAYO score at admission, UC location, smoking, previous hospitalizations, hemoglobin levels or fever upon admission., 25 patients responded to second line biological therapy (15 Infliximab, 8 Cyclosporine, 2 Tofacitinib) while, 13 failed this therapy (6 Infliximab, 7 Cyclosporine).
The only factors predicting second line therapy failure were previous biological therapy (p=0.01) and pancolitis at presentation (p=0.04).

Conclusion
ASUC patients previously treated with biologics and who had pancolitis at diagnosis are at higher risk of second line therapy failure and colectomy.
P382 Novel Image Enhanced Endoscopy (IEE) technologies for surveillance of colonic Inflammatory Bowel Disease: A pilot study evaluating Texture and Colour Enhancement Imaging (TXI) and Linked Colour Imaging (LCI) as compared with chromoendoscopy
Authors: Picardo S , Menon S , So K , Venugopal K , Cheng W , Ragunath K 
Published: January 2022

Abstract

Background
Colorectal cancer is a serious complication associated with long-standing inflammatory bowel disease (IBD). Current guidelines recommend routine surveillance with dye-spray chromoendoscopy (CE) to facilitate early detection of premalignant lesions. Novel image enhanced endoscopy (IEE) technologies, including Linked Colour Imaging (LCI) (Fujifilm) and Texture and Colour Enhancement Imaging (TXI) (Olympus), alter the way light interacts with tissue and have been demonstrated to improve adenoma detection in screening colonoscopy. We evaluated these technologies in the surveillance of IBD.

Methods
Patients that met Australian criteria for IBD surveillance, at a tertiary IBD centre, between January and October, 2021, were enrolled to undergo colonoscopy with either LCI or TXI, followed immediately by CE. Each colonic segment was examined with the respective IEE and all lesions identified were photographed and classified according to Paris and JNET classifications. Lesions were endoscopically characterised as neoplastic or non-neoplastic with the aid of additional IEE characterisation modes, Narrow Band Imaging (NBI)(Olympus) and Blue Light Imaging (BLI)(Fujifilm). Each segment was then examined with CE (methylene blue, 0.1%) and all lesions identified were classified and resected. Diagnostic yield, missed lesions and accuracy in characterising neoplastic lesions were calculated for each modality.

Results
25 patients, median age, 49 years, 52% male, were included., 16 underwent surveillance with TXI and, 9 with LCI. Patient and procedural characteristics are summarised in Table, 1. TXI identified, 22 lesions (8 neoplastic) and LCI, 11 lesions (3 neoplastic) (Table, 2)., 3 non-neoplastic lesions were missed by IEE and subsequently identified with CE (2 TXI and, 1 LCI). These were all small (&lt;5mm) non-polypoid lesions. Neoplastic lesions were identified in, 5 patients with an overall detection rate of, 20%., 2 lesions (1 TXI/NBI, 1 LCI/BLI) were characterised endoscopically as non-neoplastic but subsequently confirmed as neoplastic (both sessile serrated lesions)., 5 lesions (4 TXI/NBI and, 1 LCI/BLI) were characterised as neoplastic but subsequently confirmed as non-neoplastic (4 inflammatory and, 1 hyperplastic) (Table, 3). IEE had a sensitivity, specificity, and accuracy of, 82%, 77% and, 79% respectively, in prediction of neoplastic lesions.

Conclusion
The novel IEE modalities TXI and LCI are effective in colonic IBD surveillance with no neoplastic lesions missed as compared to CE. Overall neoplastic lesion detection rate was, 20%. The utility of IEE to accurately characterise neoplastic potential was, 79%. A larger randomised controlled trial comparing these novel technologies to CE is required and may eliminate the need for CE in the future.
P398 Long term efficacy and safety of ABP, 501 adalimumab biosimilar in inflammatory bowel diseases: preliminary results from the ADASWITCH study
Authors: Cingolani A , Felice C , Lombardi G , Onidi F M , Checchin D , Colucci R , Grossi L , Ferronato A , Rocchi C , Ascolani M , Binaghi L , Dore M F , Fanini L , Bulajic M , Mocci MD FRCP G 
Published: January 2022

Abstract

Background
Adalimumab (ADA) biosimilars have been developed to have a much lower financial cost than ADA originator.
The aim of this study was to evaluate the long term efficacy and safety of Adalimumab biosimilar ABP501 in naïve or switched Inflammatory Bowel Diseases (IBD) outpatients in Italian non-tertiary IBD centres

Methods
The ADASWITCH study is a multicentric retrospective observational study. Patients treated with Adalimumab ABP501 and with complete clinical, laboratory and endoscopic data, and a minumum follow-up of, 6 months were included. The primary objective was to evaluate the efficacy (defined as persistence on therapy with Adalimumab ABP501) and the safety (rate of adverse events) occurring during treatment.

Results
A total of, 117 IBD patients were included:, 83 with Crohn’s disease (CD, 38 F, 45 M, 71% naïve) and, 34 with Ulcerative colitis (UC, 16F, 18 M, 61.8% naïve naïve) were included. ABP, 501 showed more efficacy in maintaining clinical response at, 2 years in CD (64 pts, 77,1%) rather than in UC (22 pts, 64,7%, p=0.001) and in antiTNF (tumor necrosis factor) naïve (63 pts, 78%) rather than in antiTNF experienced patients (27 pts, 72%, p=0.0014), while no difference was seen in efficacy between ADA-switched and ADA-naïve patients. Nine patients (8 CD, 1 UC, overall, 7,7%) had adverse events that led to drug discontinuation.
Colonic localisation seems to be a predictor of not sustained clinical response (p=0,002).

Conclusion
APB, 501 adalimumab biosimilar showed high rates of efficacy and a good safety profile, in both naïve and shifted IBD patients.
P400 Evolution of clinical and pharmacological parameters after switching from intra-venous to subcutaneous infliximab in patients with inflammatory bowel disease: the REMSWITCH study
Authors: Buisson A , Nachury M , Reymond M , Yzet C , Wils P , Payen L , Manlay L , Pereira B , Fumery M 
Published: January 2022

Abstract

Background
Owing to similar efficacy, switching from intravenous (IV) to subcutaneous (SC) infliximab (IFX) is an attractive option, but the feasibility of switching patients with intensified IFX therapy remains unknown.
We assessed the clinical and pharmacological evolution after switching from IV to SC IFX in IBD patients to evaluate the feasibility and to determine the equivalence between IV and SC doses.

Methods
All IBD patients in clinical remission (CDAI &lt;, 150 or partial Mayo score ≤, 2) were consecutively included in, 3 IBD centers and were switched to SC IFX, 120mg/2 weeks (wk) (regardless of IV dose) at the theoretical day of IV infusion (visit, 0 = V0) and were followed every, 4 to, 8 weeks according to the initial IV regimen for, 6 months.

Results
Among, 246 screened patients, 65 (26.4%) were not eligible (no clinical remission or physician’s decision), and, 71.8% (130/181) accepted to switch to SC IFX (Crohn’s disease = 73,1%, concomitant immunosuppressant = 25.4%, median faecal calprotectin = 35 µg/g [16–104])., 43.1% of the, 130 patients received, 5mg/kg/8 wk.
In, 130 patients, clinical relapse leading to therapeutic escalation was observed in, 11.1% including, 4.0%, 8.6%, 11.1% and, 40.0% in patients treated with, 5mg/kg/8wk, 10 mg/kg/8wk, 10mg/kg/6 wk and, 10mg/kg/4 wk, respectively. Dose increase (240 mg/2 wk) induced clinical remission in, 92.3% of relapsers.
Infliximab trough levels (TL) were significantly higher after switching from IV to SC IFX:, 9.8 ±6.4 vs, 14.4 ±5.7 (p&lt;0.0001). TL increased in patients receiving, 5 mg/kg/8 wk (6.3 ±, 3.4 vs, 14.7 ±5.7; p&lt;0.0001) or, 10 mg/kg/8 wk (8.4 ±5.6 vs, 13.7 ±6.6; p=0.001) but remained stable in those treated with, 10 mg/kg/6 wk (11.1 ±7.6 vs, 13.1 ±5.1; p=0.31) or, 10 mg/kg/4 wk (17.8 ±4.2 vs, 15.8 ±4.6; p=0.12) (Figure, 1).

Infliximab TL remained stable (variation V1-V0 &lt; ±, 1) in, 4.3%, 15.0 %, 33.3 % and, 50.0 % of the patients with the following IV doses:, 5 mg/kg/8 wk, 10 mg/kg/8 wk, 10 mg/kg/6 wk and, 10 mg/kg/4 wk, respectively (p=0.003). No patient developed anti-IFX antibodies.
TL before the switch (8.4 ±5.6 for non-relapsers vs, 12.0 ±7.2 for relapsers; p=0.12) and TL after the switch (14.5 ±5.6 vs, 13.6 ±5.6; p=0.63) were not significantly associated with the risk of relapse. In contrast, the risk of relapse was higher in patients with stable or decreasing TL after the switch compared to those with increased TL (31.8% vs, 7.1%; p=0.024). The type of IBD and concomitant immunosuppressant were not associated with the risk of relapse. Patients’ acceptability was better with SC injections compared to IV infusions (10pts-acceptability numerical scale = 8.7 ±1.6 vs, 6.8 ±0.9; p&lt;0.0001).

Conclusion
Switching from IV to SC IFX is feasible and well-accepted leading to a low risk of relapse in patients with IBD.
P406 Disease clearance in patients with ulcerative colitis treated with aminosalicylates
Authors: Nascimento C , Revés J , Roque Ramos L , Carolina P , Fidalgo C , Glória L , Torres J 
Published: January 2022

Abstract

Background
Current treatment goals in inflammatory bowel disease include clinical remission and endoscopic healing. A new concept of disease clearance (DC) is emerging as a new therapeutic target in ulcerative colitis (UC). Although not yet clearly defined, it reflects a combination of clinical, endoscopic, and histological remission1. Preliminary data suggest that DC is achievable with biologic therapy. Aim: to evaluate if patients treated with, 5-ASA with DC can maintain sustained remission and the incidence of negative disease outcomes.

Methods
We performed a retrospective cohort study including adult patients with confirmed UC treated with, 5-ASA. Patients performing colonoscopy with biopsies between, 2017 and, 2019, with at least, 1 year of follow-up were eligible for inclusion. DC was measured at baseline and was defined as clinical (partial Mayo score ≤2), endoscopic (endoscopic Mayo score ≤1) and histological remission (chronic inactive/quiescent colitis)1. Negative disease outcomes included need for systemic steroids, therapy escalation (immunomodulators and/or biologics) and UC-related hospitalization or surgery during follow-up. Kaplan-Meier analysis was performed.

Results
We included, 56 patients with UC treated with, 5-ASA and with DC at baseline. Mean age at diagnosis was, 41.2 ±, 15 years, 59% (n=33) were female and mean disease duration was, 6.9 ±, 7.3 months. History of smoking (current or former) was present in, 36% (n=20) of the patients. Most of the patients (54%) presented with left-sided colitis. Mean follow-up was, 34.6 ±, 10.7 months. During the follow-up, 14.3 % (n=8) had a negative outcome (flare requiring systemic corticosteroids (n=6), therapy escalation to immunomodulator or biologic treatment (n=6) or hospitalization (n=1)). None of the patients needed surgery. Negative outcomes were associated with shorter disease duration (3.4 vs, 7.4 years, p=0.003). No other factors were associated with the outcomes namely sex, UC extent, smoker status, age at diagnosis or previous use of corticosteroids. There was no difference on prognosis between patients with baseline endoscopic Mayo score, 0 or, 1 (p=, 0.066). In the survival analysis, the cumulative probability of maintaining remission was, 76% at, 3 years.

Conclusion
DC in UC patients treated with, 5-ASA was associated with a high cumulative probability of maintaining remission, suggesting that the benefits of such stringent endpoint may be independent of the therapy used.

Reference
1. S Danese, S Schreiber, E Loftus, Jr., J F Colombel, L Peyrin-Biroulet, C Agboton, D Lindner, R Lirio, B Sands, P271 Evolving Targets in Ulcerative colitis: Defining Disease Clearance in the VARSITY Study, Journal of Crohn’s and Colitis,Volume, 15, Issue Supplement1, May, 2021, Page S305
P431 Early mucosal healing at week, 10 with ozanimod predicts clinical outcomes at week, 52: Post hoc analysis of the phase, 3 True North clinical trial
Authors: Reinisch W , Axelrad J , Ahmad H A , Pondel M , Ather S , Elegbe A , Sninsky C , Longman R 
Published: January 2022

Abstract

Background
Ozanimod, a sphingosine, 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, is approved in multiple countries for the treatment of relapsing multiple sclerosis and in the United States for the treatment of moderately to severely active Ulcerative Colitis (UC). A treat-to-target strategy for Inflammatory Bowel Disease (IBD) has been outlined in the Selecting Therapeutic Targets in IBD (STRIDE-II) consensus recommendations. Mucosal healing was identified as an important treatment target and may be associated with improved patient (pt) outcomes. Here we assess the relationship between early mucosal healing at week (wk), 10 and clinical outcomes at wk, 52 in ozanimod-treated pts with moderately to severely active UC in the phase, 3 True North trial (NCT02435992).

Methods
A subset of pts in True North were randomised to and/or received oral ozanimod, 0.92 mg (equivalent to ozanimod HCl, 1 mg) during the, 10-wk induction period, achieved clinical response at wk, 10 and continued ozanimod during the maintenance period. For this post hoc analysis, we examined clinical remission, corticosteroid (CS)-free remission, and mucosal healing at wk, 52 in pts with versus without mucosal healing at wk, 10. Clinical remission was defined as rectal bleeding subscore = 0, stool frequency subscore ≤1 (and ≥1-point reduction from baseline), and mucosal endoscopy subscore (MES) ≤1 without friability. CS-free remission was defined as remission with no CS use for ≥12 wk. Mucosal healing was defined as MES ≤1 without friability and a Geboes score &lt;2.0.

Results
Demographics and disease characteristics were generally well balanced between ozanimod-treated pts with (n=44) and without (n=186) mucosal healing at wk, 10, albeit a higher proportion of pts without mucosal healing had prior biologic exposure. Higher proportions of ozanimod-treated pts who achieved mucosal healing at wk, 10 had clinical remission, CS-free remission, and mucosal healing at wk, 52 versus pts who did not achieve mucosal healing at wk, 10 (Figure). Among the ozanimod-treated pts who did not achieve mucosal healing at wk, 10, 24.2% went on to achieve mucosal healing at wk 52.

Conclusion
Using a novel, stringent definition for mucosal healing, which requires endoscopic improvement and histologic remission (Geboes &lt;2.0), ozanimod-treated pts who achieved mucosal healing at wk, 10 had improved clinical, endoscopic, and histologic outcomes at wk, 52. A proportion of pts who did not reach mucosal healing at wk, 10 benefited from longer ozanimod treatment, achieving mucosal healing at wk 52.