bluuebunny/crossref_metadata_2025_split huggingface dataset:
P678 Ustekinumab therapy improves the nutritional status in patients with Crohn's Disease. A prospective study
Authors: Bertani L , D'Alessandro C , Fornili M , Coppini F , Zanzi F , Carmisciano L , Geri F , Baiano Svizzero G , Ceccarelli L , Mumolo M G , Baglietto L , Bellini M , Costa F , De Bortoli N 
Published: January 2023

Abstract

Background
Patients with Crohn’s disease (CD) display high rates of nutritional deficiencies and metabolic imbalances, primarily due to mucosal damage induced by inflammation. In particular, the loss of lean muscle mass configures a condition known as sarcopenia, which is not necessary associated with a low Body Mass Index (BMI). The presence of sarcopenia has been associated with a worst outcome of IBD. At present, no studies evaluated the impact of Ustekinumab (UST) in terms of its effects on body composition. The aim of this prospective study was to evaluate whether UST treatment could modify the parameters of body composition assessed by Bioelectrical Impedance Assay (BIA) in patients with CD. In particular, we evaluated phase angle, which represents the most clinically established impedance parameter and it might be considered as a reliable and optimal marker of nutritional status.

Methods
We prospectively enrolled all consecutive CD patients treated with UST at our center, following the current guidelines. BIA was performed at baseline and at week 48, assessing Body Cellular Mass (BCM), total body water, phase angle and BMI. At the same time-points, a colonoscopy was performed in order to evaluate the therapeutic outcome in terms of mucosal healing, defined as a Simple Endoscopic Score for CD &lt;2. We evaluated also clinical remission, defined as a Harvey-Bradshaw Index &lt;5 at week 48.

Results
Out of 44 patients enrolled, 26 (59%) presented clinical remission and 22 (50%) achieve mucosal healing at the end of follow up. No significant differences were observed at baseline in all the BIA parameters between responders and non-responders. Phase angle increased over time in responders, while this was not observed in non-responders (test for the interaction between time and outcome, p-value=0.010 and 0.008 for clinical remission and mucosal healing, respectively). The same differential increase was observed for BCM (test for the interaction between time and outcome, p-value=0.037 and 0.076 for clinical remission and mucosal healing, respectively). No other significant differences were observed regarding the other BIA parameters.

Conclusion
UST therapy seems to be able to modify body composition of patients with CD. In particular, the increase in phase angle in responders suggests that a significant improvement of nutritional status occurred in these patients. Our results are in line to what was shown by a previous study performed in patients with psoriasis treated with UST.
P681 Effectiveness and safety of oral Tacrolimus salvage therapy for acute severe ulcerative colitis: a retrospective study
Authors: Tamir-Degabli N , Cohen N A , Hirsch A , Fishman S , Ron Y , Thrum T , Maharshak N 
Published: January 2023

Abstract

Background
Calcineurin inhibitors are a therapeutic option in patients with acute severe ulcerative colitis (ASUC) failing to respond to intravenous steroids. There are limited data regarding the real world effectiveness of tacrolimus in this setting. We describe our experience with tacrolimus in a tertiary IBD center.

Methods
This retrospective study includes patients who were hospitalized at our center with ASUC between 2018-2022 and received tacrolimus salvage therapy. We collected demographic, clinical, and laboratory data. The primary endpoint of this study was clinical response to tacrolimus therapy leading to patient discharge. Secondary endpoints were safety of therapy and long-term effectiveness.

Results
Sixteen patients received tacrolimus therapy; 15 patients with UC and 1 patient with indeterminate colitis. The median age was 36 (interquartile range (IQR) 29-51), median disease duration 9 years (IQR 4.5-12), 10 (69%) were females, 11 (69%) had pan-colitis; 12 (75%) had previous biologic exposure. The median CRP was 44.46 mg/L (IQR 20.1-155), median albumin 3.2 g/dL (IQR 2.9-3.7).
15 patients (94%) responded to tacrolimus and were discharged, 1 patient failed to respond and underwent colectomy. Mean tacrolimus level during induction was 12.48 ng/ml (± 4.5). Following discharge, 1 patient had an exacerbation secondary to poor adherence and underwent colectomy within 2 months. 12 patients were transitioned to biologic therapy (7 vedolizumab, 3 ustekinumab, 2 adalimumab, 1 golimumab) and 1 patient to azathioprine. All 13 patients avoided colectomy with a median follow-up of 5.5 months (IQR 3-12). One patient was lost to follow up. Regarding safety, 10 patients had mild electrolyte disturbance requiring oral supplementation. No other adverse events were observed and no patient discontinued therapy due to adverse events.

Conclusion
Oral tacrolimus salvage therapy shows effectiveness and acceptable safety profile in patients with ASUC. The oral nature of this therapy provides an attractive therapeutic option in this setting.
P682 Development of anti-ustekinumab antibodies is an independent factor associated to loss of response to ustekinumab therapy in IBD patients
Authors: Roblin X , Nancey S , Bastide L , Veyrard P , Bischetti G , Berger A E , Barrau M , Paul S 
Published: January 2023

Abstract

Background
Monitoring of antibodies (ADA) under ustekinumab therapy in routine practice is not recommended in IBD patients.

Aim of study
to investigate the relationship between ADA detected by a drug-tolerant assay and loss of response to therapy in a cohort of IBD patients treated with ustekinumab.

Methods
This was a retrospective study enrolling consecutively all adult patients with moderate to severe active IBD and having a follow up period of at least 2 years after ustekinumab induction. Loss of clinical response was defined as CDAI &gt; 220 or HBI &gt; 4 for CD and partial Mayo subscore &gt; 3 for UC associated with the decision to modify disease management or treatment.

Results
Ninety patients were included (78 CD and 12 UC, mean age 37 years). Median levels of anti-ustekinumab antibodies (AUA) were significantly higher in patients with LOR compared with those in responder patients (15.2 µg/mL-eq CI (7.9-21.5) and 4.7 µg/mL-eq CI (2.1-10.5), respectively; p=0.04). The area under the ROC curve (AUROC) for AUA in predicting LOR was 0.76. The optimal cut-off point capable to accurately identify patients with LOR was 9.5 µg/mL-eq with a sensitivity of 80 % and specificity of 85 %. In multivariate analysis, serum AUA ≥ 9.5 µg/mL-eq (HR=0.84), prior vedolizumab exposition (HR=0.78) and azathioprine (HR=3.78) exposures were the only independent factors associated with subsequent clinical response to ustekinumab therapy.
Table 1 : univariate and multivariate analysis to isolate factors associtaed with subsequent clinical response to ustekinumab therapy

Conclusion
In our real-life cohort, AUA was identified as an independent predictor of LOR and subsequent drug failure to treatment
P698 Role of an exclusion diet (reduced disaccharides, saturated fats, emulsifiers, red and ultraprocessed meats) in maintaining the remission of chronic inflammatory bowel diseases in adults
Authors: Preda C M , Istratescu D , Manuc T , Nitescu M , Louis E , Manuc M , Stroie T , Diculescu M 
Published: January 2023

Abstract

Background
Inflammatory bowel diseases (IBD) are a main focus in current research with diet being an emerging therapeutic line due to its links both in onset and progression. A Western-style diet high in processed foods, food additives, red meat, and animal fat has been linked to a higher risk of developing IBD. The aim of this study was to establish an association between an anti-inflammatory exclusion diet and maintenance of remission in IBD. Also, we assessed the efficacy and safety of this diet compared to a non-dietary group and the possible therapeutic effect of this diet in the maintenance of IBD remission.

Methods
One hundred seventeen adult IBD patients in remission (64 patients with Crohn’s disease- CD and 53 patients with ulcerative colitis- UC) were randomized at their own will to a 6-months exclusion diet (n=32) or a habitual diet (n=85). Dietary patterns, clinical activity of the disease and inflammatory markers were assessed at baseline and at the end of dietary intervention.

Results
The acceptance rate of the exclusion diet in our cohort was 27.35% (30% in UC and 20% in CD). The exclusion diet and control populations were similar, except for immunosuppressive treatment (only 30% of patients in the exclusion diet group had an immunomodullator compared to 70% in the control group (p-value &lt;0.001)).
The clinical remission after six months was maintained in the exclusion diet arm (100%). In the control arm, 3 patients had clinically active disease (1 patient with UC and 2 patients with CD) and 80 patients maintained the clinical remission state (96.4%) (p-value = 0.278). Figure 1 is depicting the remission rates in different patient groups. Regarding biochemical markers, erythrocyte sedimentation rate (ESR) at baseline was higher in the exclusion diet arm: 31 (5-62) than in the control arm 14.5 (4-48) (p-value=0.011), but six months after, the groups were similar (p-value = 0.440). Fecal calprotectin at baseline was higher than 300 micrograms/gram in 30% of cases in the exclusion diet arm and in 25.8% of cases in the control arm (p-value = 0.774). Six months after, 50% of cases had a higher fecal calprotectin (&gt;300 micrograms/gram) in the intervention arm and only 20.5% in the control arm (p-value = 0.033).
Figure 1. Maintenance of clinical remission 6 months after intervention

Conclusion
We found a better trend of sustained clinical remission in patients who follow an exclusion diet.
However, the threshold for statistical significance was not achieved.
The clinical study continues, these are preliminary data.
There is also a trend of improvement in ESR in the intervention group, but the levels of fecal calprotectin did not improved.
P701 A time-to-event model relating infliximab trough concentrations to the risk of relapse after extending the infusion interval
Authors: Kantasiripitak W , Outtier A , Thomas D , Sabino J , Vermeire S , Ferrante M , Dreesen E 
Published: January 2023

Abstract

Background
Extending the infliximab infusion interval has been attempted in patients with Crohn’s disease (CD) and ulcerative colitis (UC) who sustained treatment response following an earlier interval shortening. We aimed to identify predictors of sustained remission after infliximab interval extension.
Methods: Data from 30 adult patients (17 CD, 13 UC), who underwent infliximab interval extension following earlier interval shortening, were collected from a single-centre database search. All patients were in steroid-free clinical (two-item patient-reported outcome [PRO2] ≤1 [UC] and ≤8 [CD]) and biological (C-reactive protein [CRP] &lt;5 mg/L or faecal calprotectin [FC] &lt;250 mg/kg) remission at interval extension. Time-to-relapse was modelled using a time-to-event (TTE) model with loss of steroid-free clinical and biological remission being the event of interest (NONMEM7.5). Various hazard functions were explored, and disease type, time-varying infliximab concentrations and infliximab clearance were investigated as predictors of the relapse hazard risk. The infliximab clearance was calculated using weighted averaging of the estimates of 18 population pharmacokinetics models.1

Results
In total, 37% of patients (n=11) remained relapse-free until one year after infliximab interval extension (Figure 1). A time-constant (exponential) hazard model proved best to describe the relapse data of patients with CD (Figure 2, Table 1). The Gompertz hazard model best described the data of patients with UC, with the relapse hazard risk increasing over time. Patients with CD had an overall higher relapse hazard risk than patients with UC. For patients with UC, the infliximab trough concentration was negatively related to the relapse hazard risk and was included in the model using a sigmoidal inhibitory Emax function. Also, in patients with UC, a higher infliximab clearance was associated with an increase in the relapse risk. The infliximab clearance was also a predictor of the relapse hazard risk, but its effect could not be precisely estimated.

Conclusion
Patients with CD had a higher relapse risk than patients with UC. Only in patients with UC, the hazard risk increased with time, but this risk was lower when the infliximab trough concentration increased. No exposure-response relationship was observed in patients with CD. Results of this exploratory analysis should be interpreted with care and prospective confirmation is awaited (MODIFI study; NCT04982172).2
1Kantasiripitak W. et al. CPT PSP. 2022
2Sheiner LB. et al. CPT. 1997
P702 Clinical and biomarker remission is maintained after switch from monthly dosed intravenous to subcutaneous maintenance treatment with vedolizumab in Inflammatory Bowel Disease
Authors: Pintar S , Hanžel J , Smrekar N , Koželj M , Drobne D , Kurent T , Štabuc B , Novak G 
Published: January 2023

Abstract

Background
Background: Subcutaneous (SC) formulation of vedolizumab (VDZ), a gut selective integrin antagonist used for treatment of inflammatory bowel disease (IBD), has proven effective and safe in clinical trials after intravenous (IV) induction. However, it is not clear if patients can be effectively switched from IV maintenance treatment to SC. We aimed to assess real-world efficacy of switch from IV to SC formulation and to investigate if baseline maintenance regimen (every 8 weeks (q8) versus every 4 weeks(q4)) impacts outcome after switch.

Methods
Methods: In this observational study at a tertiary referral centre, we enrolled 126
prospectively followed consecutive adult patients with IBD who were switched to SC VDZ maintenance treatment. We included patients after IV induction (2 or 3 infusions) and patients who switched from IV maintenance treatment q8 and q4. SC VDZ dosing was 108 mg every 2 weeks regardless of the previous IV regimen. Clinical (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) and partial Mayo score (pMayo) for ulcerative colitis (UC)) and biochemical disease activity (CRP, fecal calprotectin (FC)) were assessed at the time of switch and at first and second follow-up. HBI&lt;5 and pMayo&lt;2 were considered clinical remission. CRP &lt;5mg/L and FC&lt;150mg/kg were considered biomarker remission.

Results
Results: In total 126 patients (40% CD, 60% UC) were switched to SC vedolizumab. Demographics and baseline characteristics are presented in Table 1. Median time to 1st follow up (FU) was 14,5 weeks (IQR 12-26) and median time to 2nd FU was 40 (IQR 36-52) weeks. From all patients, 8/126 (6%) discontinued SC VDZ treatment, 5 of them due to endoscopically active disease (2 in IV induction group, 3 in q4 group), 1 had dysplasia and required surgery (IV induction group), two others (both q8 group) discontinued on their wish. In patients who continued SC treatment clinical and biomarker remission appears to be maintained at 1st and 2nd FU. Clinical and biomarker outcomes are presented in Table 1. Vedolizumab concentrations were 16.9, 24.6 and 13.0 at baseline, 27.0, 25.3 and 25.2 at 1st FU and 25.5, 34.6 and 22.1 at 2nd FU in the q8, q4 and IV induction group, respectively.

Conclusion
Conclusion: The results of this real-world study suggest maintenance of clinical and biomarker remission in patients switched from IV to SC vedolizumab. Baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.
P703 Real world experience of the transition from the intravenous to subcutaneous formulation of vedolizumab in inflammatory bowel disease: A review of current data
Authors: Agboton C , Kamble P 
Published: January 2023

Abstract

Background
Vedolizumab (VDZ), a gut selective antilymphocyte trafficking anti-α 4β 7 integrin monoclonal antibody indicated for the treatment of IBD. After a 3 doses induction, maintenance can be achieved with a standard 8-weekly (Q8W) regimen, or–at any time during the maintenance– patients can be transitioned to 108 mg subcutaneous (SC) formulation at a standard 2 weekly (Q2W) regimen.

Methods
This was a literature review to identify real-world studies on the transition from the IV to SC VDZ. The Pubmed and Embase databases were searched up to October 2022 to identify publications on real-world data on the transition from IV to SC VDZ.

Results
In total, 9 studies were identified with a total of 1,323 IBD patients in the UK (5 studies), Norway, Sweden, Belgium and The Netherlands1-9. Two prospective studies reported no loss of effectiveness based on disease activity scores of VDZ after the IV-SC transition 1,2, along with maintenance of baseline status (status at the time of transition) reported in 84% of patients1. Biomarkers stability, including fecal calprotectin and C-reactive protein, were reported in three studies3-5. Persistence with VDZ treatment following IV-SC transition was 96% at 6 months and 89% at 12 months in one study3, while another study reported persistence of 86% at 6 months6. A preference for the SC formulation by patients was reported 59% and 56% in two studies7,8, with time savings and fewer hospital visits recorded as the main reasons for preference of the SC formulation7. Multivariate analysis of patient characteristics in two studies7,8 revealed no factor associated with preference for VDZ SC other than younger age in one study8. The most frequently reported adverse events with VDZ SC were injections site reactions: 15% and 18% in two studies1,5, with transient severe injection site reactions reported in 1% of patients in one study3.

Conclusion
Real-world data on IBD patients who transitioned from IV to SC VDZ showed no change in effectiveness, with a majority preferring the SC formulation due to time savings and the transition leading to fewer hospital visits. Safety of VDZ SC was generally comparable with that of IV VDZ.
References:
1. Ventress E et al J Crohn’s Colitis 2022;16:911-21
2. Volkers A et al Aliment Pharmacol Ther 2022;56:1044-54
3. Bergqvist V et al Aliment Pharmacol & Ther 2022;55:1389-1401
4. Mclean M et al Gut 2022;71:A58-A59
5. Wiken T et al J Crohn’s Colitis 2022;16:i378-79
6. Lim S et al J Crohn’s Colitis 2022;16:i499-i500
7. Alice H et al J Crohn’s Colitis 2022;16:i410
8. Asnong K et al J Crohn’s Colitis 2022;15:S608-9 9. Maw F et al Gut 2021;70:a91
P705 Switching from intravenous to subcutaneous infliximab: clinical and patient experience outcomes
Authors: Nowell E , Laird S , Bailey E , Brownson E , Saunders J , Seenan J P , Smith G , Macdonald J 
Published: January 2023

Abstract

Background
Intravenous (IV) infliximab (IFX) monotherapy is associated with significant loss of response. Therapeutic drug monitoring shows an association with low serum trough drug levels and development of anti-IFX antibodies. Combination therapy with immunomodulators is not always possible, and IFX dose escalation leads to higher drug costs and time pressure on infusion units. Both approaches have raised heightened patient safety concerns due to the Covid-19 pandemic.
Subcutaneous (SC) IFX pharmacokinetics lead to improved drug trough levels, which could lead to better clinical outcomes.

Methods
The NHS Greater Glasgow and Clyde biologics database was used to identify selected patients currently treated with IV IFX for IBD for suitability for SC switch. Patients were contacted to allow informed choice to opt in or out of switch.
Baseline clinical data was collected, and patients were reviewed at week 8 and week 24 for assessment of clinical disease activity scores, IFX trough levels/anti-drug antibody levels, and faecal calprotectin. Patient experience outcomes were assessed using a quality of life questionnaire (CUCQ-8).

Results
31 patients consented to switch; F:M = 17:14. The majority of patients (16) had Crohn’s disease, with 13 with UC and 2 IBDU. Mean duration of disease was 9.1 years and duration of prior IV therapy was 3.3 years. 28 patients were reviewed at week 8 and 24 at week 24.
At week 24, 71% of patients were in clinical remission (Harvey-Bradshaw index score &lt;5 or partial Mayo score &lt;2), 96% had CRP &lt;5 mg/Land 87% had FCP &lt;250µg/g. 21% of patients had subtherapeutic IFX trough levels at baseline, all had increased by week 8 and there were no subtherapeutic levels measured by week 24. One patient had detectable antibodies at week 24, compared with 9 patients at baseline.
Three patients required oral steroid therapy during the 24-week follow up period. There were no hospital admissions, significant infections or adverse reactions within the cohort.
15 patients submitted CUCQ-8 scores, of these 7 patients’ scores had worsened at week 8 but by week 24 13/15 were stable or improved compared to baseline.

Conclusion
Switching from IV to SC infliximab is welcomed by most patients. The efficacy, tolerability, increased drug level and safety which has previously been demonstrated is reproduced in our cohort. This study is the first to explore patient experience outcomes. The finding of initial worsening of the CUCQ-8 score, but overall improvement by week 24 opens further opportunity for engaging patient involvement in switch programmes.