bluuebunny/crossref_metadata_2025 huggingface dataset:
P318 Safety of Biological Therapies in Elderly IBD: a Systematic Review and Meta-analysis
Authors: Drügg Hahn G , Golovics P , Wetwittayakhlang P , Santa Maria D , Britto U , Wild G , Afif W , Bessissow T , Bitton A , Lakatos PhD P L
Published: January 2022

Background

There was a significant progress in the medical therapy of inflammatory bowel diseases(IBD) with the advent of biological compounds, yet patients may experience adverse events(AE): infusion/injection reactions, infections and malignancies, understudied in vulnerable patient populations (e.g. elderly).

Methods

We systematically searched PubMed/Medline and conferences proceedings between January, 1, 2010, and June, 1, 2021, to identify eligible studies that examined the safety of biologic therapies in elderly patients with IBD. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Search was focused on MESH Terms including IBD/CD/UC, biological therapy, adverse events, infections, infusion/injection reaction and malignancy and elderly.

Results

Our search identified, 2885 articles and, 12 congress abstracts trough the data base search, finally, 14 peer reviewed papers and, 3 abstracts met the inclusion criteria. Most studies were retrospective, merging CD and UC patients, with an age limit of, 60 or, 65 years for elderly, from Europe or North America. According to our meta-analysis the rates of AE were not different according to the type of biologics (mean rate:, 11.3 (CI, 95%, 9.9–12.7)/100 pts years; p=0.11) in elderly IBD patients with the use of anti-TNF, vedolizumab(VDZ) and ustekinumab(UST). Similarly, rates of infection (mean rate:, 9.5 (CI, 95%, 8.4–10.6)/100 pts years; p=0.56). On the other hand, regarding infusion/injection rates were more common in patients on anti-TNFs (mean rate:, 2.51 (CI, 95%, 1.7–3.4/100 pts years; p=0.02) and malignancy rates were higher in elderly patients on VDZ/UST (mean rate:, 2.14 (CI, 95%, 1.6–2.8)/100 pts years; p=0.01). Two studies directly comparing anti-TNF and VDZ reported similar efficacy and safety in the elderly IBD population.

(p=0.56; Total: reflects patient year of follow-up.)

Conclusion

We report the first meta-analysis on the comparative safety of biological therapies in elderly IBD patients. Rates of adverse events and infections were not different across the biologics. In contrast, infusion/injection reactions were more common in patients on anti-TNFs. Current data are insufficient to suggest sequencing among biologicals in the elderly based on the safety, larger studies in elderly IBD population are warranted.
P325 Performance of new MRI scores: the modified Van Assche Index and the MAGNIFI-CD in the evaluation of the response to anti-TNFα in anoperineal fistulas in Crohn’s disease
Authors: Mtir M , Hassine H , Kahlaoui F , Cherif D , Tlili R , Kchir H , Maamouri N
Published: January 2022

Background

Despite considerable therapeutic advances over the last two decades in the management of Crohn’s disease(CD), complex anoperineal fistulas(APF) still constitute a real therapeutic challenge for the practitioner. Treatment is mainly medico-surgical, combining seton drainage and biotherapy. The ultimate goal is to obtain a deep remission, which combines clinical remission and a normal perineal MRI. Thus, several MRI scores have been proposed to assess the therapeutic response of APF to biotherapy.

The aim of this study was to investigate the reliability of the new MRI scores: the modified Van Assche Index(mVAI) and the MAGNIFI-CD in the evaluation of the response of APF to anti-TNFα, by comparing them to the old version of the Van Assche Index(VAI).

Methods

We conducted a retrospective study, including all patients followed up for CD with APF treated with anti-TNFα over a, 10-year period [2010–2020]. Clinical, biological, morphological and evolutionary data were collected. VAI, mVAI and MAGNIFI-CD scores were calculated from data provided by perineal MRI: number, locations, extensions and lengths of fistulous tracts, characteristics of collections. Clinical response to anti-TNFα was assessed by proctological examination, at the end of which the patients were classified into two groups:

• Responders(26): having a complete remission (closure of all initially productive fistulous orifices) or partial response (closure of more than, 50% of orifices)

• Non-responders(12): closure of less than, 50% of the initially productive fistulous orifices

A statistical study was carried out to compare the performance of the different scores in assessing the response to treatment by calculating the area under the ROC curve with a, 95% confidence interval.

Results

A total of, 38 patients were included. The mean age was, 42 years [26–73] and the sex-ratio M/F was, 0,4. All patients had received anti-TNFα after disappearance of perineal collections if initially present (Infliximab in, 35 cases(92,1%) and Adalimumab in, 3 cases(7,9%)) combined with thiopurines in, 97,4%. The average duration of anti-TNFα therapy was, 46 months [5–180]

The means of the different scores were calculated in responders and non-responders before and after anti-TNFα treatment respectively:

A decrease in all three scores was observed after anti-TNFα treatment in the responders, in contrast to the non-responders, thus confirming therapeutic failure.

Furthermore, the AUROC of the VAI, mVAI and MAGNIFI-CD scores in the assessment of response to anti-TNFα in APF were, 0,925, 0,908 and, 0,869 respectively.

Conclusion

Our results suggest that the old version of the VAI, as well as the mVAI and MAGNIFI-CD, are reliable scores with comparable performance in the assessment of response to treatment in APF in CD.
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

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<0.01). In comparison with BF with TC-1, the availability of TC0 significantly lowered the chance of falsely predicting TC+1 <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

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] <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

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

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

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 (<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

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

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 <, 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<0.0001). TL increased in patients receiving, 5 mg/kg/8 wk (6.3 ±, 3.4 vs, 14.7 ±5.7; p<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 < ±, 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<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

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

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 <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 <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.
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

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)>, 4 points and/or persistent biomarker elevation (calprotectin>, 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<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 <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

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<0.001, n=17), both in inflamed (mayo endoscopic score >1) (r=0.89, p<0.001, n=10) and uninflamed (mayo endoscopic score ≤, 1) tissue (r=0.88, p<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

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

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

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

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.