bluuebunny/crossref_metadata_2025_split huggingface dataset:
P341 Pharmacokinetics and exposure-response analyses of upadacitinib in patients with moderate to severe ulcerative colitis – Analyses of induction and maintenance clinical trials
Authors: Ponce-Bobadilla A V , Stodtmann S , Eckert D , Zhou W , Liu W , Mohamed M E 
Published: January 2022

Abstract

Background
Upadacitinib (UPA), an oral selective and reversible JAK1 inhibitor, showed favorable efficacy and safety profile in Phase, 2b and, 3 studies in subjects with moderate to severe ulcerative colitis (UC). Population pharmacokinetics and exposure-response analyses were performed to characterize the relationships between UPA plasma exposures and key efficacy and safety endpoints using data from these studies.

Methods
The pharmacokinetics (PK), efficacy, and safety of UPA for induction and maintenance treatment in UC were evaluated in a Phase, 2b induction, two replicate Phase, 3 induction, and a Phase, 3 maintenance clinical trials. UPA PK was characterized using data from, 978 UC patients. UPA exposure-response relationships for key efficacy and safety endpoints at the end of induction and maintenance periods were characterized using data from, 1,234 and, 449 UC patients, respectively. Quartile plots and logistic regression models were used to evaluate the exposure-response relationships across UPA doses of, 7.5 mg to, 45 mg once daily (QD) for induction and, 15 mg to, 30 mg QD for maintenance.

Results
UPA PK in UC patients was consistent with other patient populations and between the induction and maintenance periods. The percentage of subjects achieving clinical and endoscopic efficacy endpoints at the end of the induction increased with increasing UPA average plasma concentration (Cavg), and became mostly flat at Cavg values approximately equivalent to the, 45 mg QD (Figure, 1). For maintenance treatment, there was a trend for increasing the percentage of subjects achieving clinical remission, steroid-free remission, endoscopic improvement, and histo-endoscopic mucosal improvement within the range of UPA plasma exposures evaluated. Exposures associated with UPA, 30 mg QD were estimated to provide a, 8% to, 10% increase in the percentage of subjects achieving these endpoints compared to, 15 mg QD (Figure, 2). There was no trend for exposure-response relationships within the range of evaluated UPA exposures for any of the evaluated safety endpoints (&gt;2 g/dL decrease in hemoglobin and &gt;2 g/dL decrease in hemoglobin and &lt; lower limit for normal, hemoglobin &lt;, 8 g/dL, lymphopenia ≥ Grade, 3, neutropenia ≥ Grade, 3, Herpes Zoster infection, serious infections, and pneumonia) at the end of induction or maintenance periods.

Conclusion
UPA plasma exposures associated with the, 45 mg QD induction dose maximized efficacy for clinical and endoscopic endpoints at Week, 8. Plasma exposures associated with UPA, 30 mg maintenance dose provide additional incremental benefit compared to, 15 mg QD. No trends were observed for increase in the evaluated safety events with increasing UPA plasma exposures at the end of induction or maintenance periods.
P346 Chronic pouch failure rates after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis
Authors: Reijntjes M , de Jong D , Bocharewicz E , Elise W , Duijvestein M , Bemelman W 
Published: January 2022

Abstract

Background
During restorative (completion) proctectomy and Ileal pouch-anal anastomosis (IPAA), rectal dissection can be performed in either the total meso-rectal excision (TME) plane with anterolateral exception, or as a full close rectal dissection (CRD). CRD showed lower postoperative morbidity and better short-term quality of life (QOL) when compared to TME. We aimed to compare the incidence of chronic pouch failure (PF) in patients undergoing TME or CRD during proctectomy followed by IPAA for inflammatory bowel diseases (IBD).

Methods
This mono-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC from January, 2002 to October, 2017 in a tertiary IBD referral centre. Outcomes of this study were chronic pouch failure (PF) rates and PF-free survival between patients who underwent CRD and TME. Chronic PF was defined as a pouch-related complication occurring &lt;, 3 months after IPAA surgery requiring pouch-redo surgery, -excision or definitive ileostomy without excision. PF-free survival was defined as months between date of functional pouch and date of surgical PF. Multivariable cox- regression was used to determine whether CRD as dissection type had impact on PF-free survival, when compared to TME. (Chronic) anastomotic ileal pouch-anal leakage and fistula were also included in analyses as confounding factors, which is in line with available literature1.

Results
Out of, 293 patients that underwent pouch surgery, 123 (42.0%) had a proctectomy in the CRD plane, and, 170 (58.0%) in the TME plane. As the median operation year for CRD was, 9 years later (2006 vs, 2015), a significantly shorter postoperative follow-up for CRD patients was reported (74 vs, 172 months, p&lt;0.01). PF occurred in, 27 (9.2%) patients, of which six (4.9%) underwent CRD and, 21 (12.4%) underwent TME (p=0.03). Both the mean PF-free survival in months (162 vs, 195, p=0.31) and PF-free survival rate after, 36 months (98.1% vs, 92.1%) were comparable among patients who underwent CRD and TME (Figure, 1, p=0.31). CRD was not associated with developing chronic PF (Odds ratio = 0.96, CI, 95%:, 0.35–2.61) after multivariable cox-regression analysis.
Figure, 1. PF-free survival curve for patients who underwent CRD (red) and TME (blue)

Conclusion
In the current study, we did not observe a significant difference in chronic PF after either CRD or TME. Although data on long-term functional outcomes and QOL are necessary to draw final conclusions, results of this study suggest that long-term outcomes of CRD were comparable to outcomes after TME. As an earlier study concluded CRD is beneficial when it comes to postoperative morbidity and short-term QOL, surgeons should consider performing close rectal dissection during IPAA surgery for IBD.
P352 Ustekinumab is associated with superior treatment persistence compared to vedolizumab in Crohn’s disease patients who failed to anti-TNF therapy: results from a Hungarian cohort study
Authors: Bacsur P , Resál T , Miheller P , Szamosi T , Schäfer E , Sarlós P , Iliás Á , Szántó K J , Rutka M , Bálint A , Fábián A , Bor R , Zoltán S , Matuz M , Molnár T , Farkas K 
Published: January 2022

Abstract

Background
Anti-tumor necrosis factor alpha treatments are effective and safe as first line therapy, however, their long-term efficacy is limited by primary (PNR) and secondary non-response (LOR) resulting in treatment discontinuation in approximately, 40–50% of cases. Vedolizumab (VDZ) and ustekinumab (UST) therapy could be good alternative in patient with anti-TNF failure, however, no direct comparison has been made. This study aimed to assess treatment persistence and long-term efficacy of VDZ and UST as second- and third line biological therapies in Crohn’s disease (CD) patients refractory to anti-TNF therapy.

Methods
In this multicentre study, CD patients on VDZ or UST maintenance therapy were enrolled. We analysed data of medical history retrospectively in case of both agents. Demographic and clinical data at baseline and one-year were obtained. Clinical (CDAI&lt;150) and biochemical (CRP&lt;10) activities and steroid-free remission were assessed while concomitant medications, hospitalisations and surgeries were recorded during the follow-up. We performed Kaplan–Meier analyses of persistence on treatment including age, CRP, CDAI at baseline, localisation, disease duration, treatment level as possible predictors.

Results
200 UST and, 96 VDZ-treated patients were included in the study. After exclusion of confounders, 162 UST and, 77 VDZ-treated patients were completed the follow-up. Mean age was, 41,1 (±16,5) and, 37,9 (±11,3) years at both agents at baseline. Steroid-free clinical and biochemical remission rates did not differ between VDZ and UST groups at one year (73% vs, 73% and, 67% vs., 51%). Kaplan-Meyer analysis revealed superiority of UST during follow up (86,5% vs., 62,9%, p&lt;0,0001). At both agents, second-line therapy was superior to third line in drug persistence (p=0,019,Exp(B)=, 0,314). None of the further examined parameters predicted treatment outcome. Therapies were terminated due to PNR in, 14 (18%) vs., 8 (5%) cases, while LOR appeared at, 13 (17%) vs., 12 (7,4%) cases at VDZ and UST treatment. One patient discontinued UST therapy due to adverse drug reaction at w20. Other drug-associated adverse reactions didn’t occur during the follow-up. During the follow-up surgery was indicated in, 6 and, 4 cases on VDZ, and, 8 and, 1 cases on UST treatment due to activity and perianal disease (8 and, 5%;, 5 and, 1%, p=0,39, p=0,04).

Conclusion
We confirmed that VDZ and UST are effective and safe alternatives to CD patients who have failed to anti-TNF therapy. UST has a superiority in drug persistence compared to VDZ. Second compared to third line of sequential therapy results in better outcome in drug persistence in case of both agents, however, head-to-head comparison of both agents are needed to verify our data.
P357 Monitoring of Thiopurines and Methotrexate in Inflammatory Bowel Disease: Are we Monitoring Too Frequently? A Cross Sectional Study
Authors: Liao Y W , Oh S , Wright A , Evans C , Duff C , Farmer A , Fryer A 
Published: January 2022

Abstract

Background
The use of immunosuppressive medications such as thiopurines and methotrexate (MET) are commonly employed in inflammatory bowel disease (IBD) to control symptoms and maintain remission. The British Society of Gastroenterology recommends three monthly full blood count (FBC) and liver function tests (LFT) to monitor for myelotoxicity and hepatotoxicity after being established on therapy. However, the quality of evidence for this is low.
Due to the high burden of blood tests and patients becoming increasingly apprehensive to attend hospital or their general practice surgery in the midst of a pandemic, we aimed to investigate (1) the feasibility to adhere to these recommendations and (2) the frequency of abnormal blood test when recommendations are adhered.

Methods
We performed a, 12-month cross sectional study from July, 2017 to July, 2018 of patients established on azathioprine (AZA), 6-mercaptopurine (6-MP), or MET. The timeline was split into four windows of three months each. A patient was removed from the study if they reached any one of these six end points: no FBC or LFT checked within a window, new abnormal LFT, white cell count (WCC) less than, 3.5, change in medication, change in dosage, and medication stopped.

Results
As of, 2019, 4327 patients were under the care of our specialist IBD team with, 1081 on active therapy. We identified, 205 patients who were established on these agents (AZA = 156, 6-MP = 41, MET = 8) within the determined study period. A total number of, 96 patients reached an end point during this period.
For our first objective, a patient was deemed to have been monitored if FBC and LFT was checked at least once during a window., 26% (54/212) of patients were removed from the study as they did not fulfil this criteria.
Of the remaining, 41 patients who reached an end point, 14 were due to a new abnormal LFT result (AZA = 8, 6-MP = 6, MET = 0) and, 5 due to a WCC less than, 3.5 (AZA = 4, 6-MP = 1, MET =0). Excluding non-adherent patients, our study revealed only, 12% (19/158) of patients had to discontinue therapy due to an abnormal blood test.

Conclusion
Achieving an adherence of, 74% was possible with a team of dedicated IBD specialist nurses and doctors in a tertiary centre. Whilst there is still much room for improvement, this may be difficult to replicate in smaller centres with more limited resources.
Despite the small sample size, our finding of only, 12% of abnormal blood test is consistent with similar studies done by Fournier et.al in, 2010 and Chaparro et.al in, 2013. This would certainly pose the question if we can consider monitoring less frequently.
P393 Efficacy and Safety of Induction Therapy With Calcineurin Inhibitors in Combination With Ustekinumab for acute severe colitis
Authors: Veyrard P , Pellet G , Laharie D , Nachury M , Juillerat P , Altwegg R , Nancey S , Fumery M , Allez M , Tran minh M L , Roblin X 
Published: January 2022

Abstract

Background
Ulcerative colitis is a chronic inflammatory bowel disease., 20% of patients will experienced acute severe colitis during their life. In acute severe colitis, when IV steroids failed, two strategies can be used with equivalent efficacy: Ciclosporin and Infliximab. Recently, Pellet et al reported the interest of association ciclosporin – vedolizumab. Regarding results from Varsity trial, more patients are treated before a CAG with vedolizumab. Recently, UNIFI trial showed the interest of ustekinumab in UC patients. So, it should be interesting to analyze the interest of the association Ciclosporin -Ustekinumab in case of acute severe ulcerative colitis. In this study, we retrospectively evaluated the clinical response and the rate of colectomy when we used anticalcineurin and Ustekinumab in acute severe colitis refractory to IV steroids.

Methods
All patients with acute severe colitis who failed to IV steroid and who were treated with calcineurin inhibitor and Ustekinumab, can be included. They were treated with a, 6mg/kg infusion and then a, 90mg subcutaneous injection every, 8 weeks. Eight referral French center and a Switzerland referral center were involved in this study. The primary endpoint was clinical response at, 6 months. We also evaluated the rate of colectomy and survival without Ustekinumab discontinuation. We reported also adverse events in this cohort.

Results
Eleven patients were included., 82% were women, with a median age of, 32.2 years (range, 25.5–36.5 y). The median disease duration was, 8.2 years (range, 3–9.5 y). Ten patients failed to Infliximab and, 9 to Vedolizumab. At inclusion, median Lichtiger score, Mayo score and CRP were respectively, 13,4 [IC95, 12.5–14.5], 10.6 [IC95, 10–11.5] et de, 24.5 mg/L [IC95, 4.5–35.7mg/l]. The mean Endoscopic Mayo score was, 2.6 +/-0.7. The median time between beginning of Calcineurin inhibitor and Ustekinumab was, 22 days (minimum, 6d, maximum, 128d). Median follow-up was, 11 months. None of the patients underwent colectomy at, 6 months. The mean full Mayo score was significantly lower during the follow-up (10.6 at baseline and, 1.0 at, 6 months; p = 0.005). The mean CRP level was significantly reduced (from, 24.5 mg / L [CI95, 4.5–35.7] to, 2.6 mg / L [2–3.1], p = 0.02). Only one patient stopped ustekinumab at the end of follow-up. Two patients required treatment optimization. Tolerance to treatment was well with only one case of alopecia described without withdrawal of treatment.

Conclusion
In this retrospective study including patients hospitalized for IV Steroid-resistant acute severe colitis, the sequence of treatment with induction anti-calcineurin with ustekinumab therapy appears to be effective and well tolerated. These results need to be confirmed on a larger number of patients.
P396 COVID-19 pandemic-related endoscopy delays did not translate to deleterious outcomes for patients with Inflammatory Bowel Disease: A retrospective cohort study
Authors: Chambers J , Gurpreet M , Maria M , Reena K , Aze Suzanne W 
Published: January 2022

Abstract

Background
Inflammatory Bowel Disease (IBD) patients require frequent endoscopies for disease assessment and confirmation of remission, making it a crucial component in their management. It is unknown if measures put in place to reduce the spread of the virus SARS-CoV-2, including the delay of non-urgent IBD patient endoscopy, resulted in more deleterious outcomes for patients with IBD. Therefore, we aimed to determine if delays in endoscopy during the COVID-19 pandemic were associated with an increased risk of adverse IBD outcomes (emergency room, ER presentation, hospitalization, surgery or escalation of drug therapy).

Methods
A retrospective cohort study was performed in IBD patients receiving outpatient endoscopies between March and August, 2019 (pre-COVID-19 pandemic) and, 2020 (during the COVID-19 pandemic) at two tertiary care centers affiliated with Western University, London, Canada. Data pertaining to endoscopy timing, IBD drug prescription, ER attendance, hospitalization, and surgery were collected.

Results
A total of, 1160 endoscopies (2019, n=718;, 2020, n=442) occurred across, 1083 patients (2019, n=669;, 2020, n=414). More endoscopies were delayed in, 2020 than, 2019 (26.7% vs., 9.7% respectively, p&lt;0.0001) and for longer, 56 days (IQR=63) in, 2020 vs., 30 days (IQR=42) in, 2019. No differences were seen in the baseline demographic characteristics based on cohort year or occurrence of endoscopy delay. Also, rurality, sex, IBD type, and age were not associated with a delay in endoscopy. It was found that endoscopy delay was not associated with an increased risk of an adverse IBD outcome (composite outcome of emergency room presentation, ER presentation, hospitalization, surgery or escalation of drug therapy) (RR, 1.23, p=0.20).

Conclusion
A greater proportion of delays in endoscopy were observed during the COVID-19 pandemic; however, delays in general were not associated with more adverse IBD outcomes, and were found to be associated with less deleterious IBD outcomes. This may reflect the accurate and preferential triage of more severe IBD patients to endoscopic assessments.
P399 C-Reactive Protein Values After Surgery for Inflammatory Bowel Disease: Is It Still A Good Marker For Intra-Abdominal Complication? A Retrospective Cohort Study of, 347 procedures
Authors: Gaspard B , Alexandre C , Thibault V , Lauren O , Clotilde D , Najim C , Yann P , Lefevre J 
Published: January 2022

Abstract

Background
C-reactive protein (CRP) is a useful predictive test to early detect abdominal complication after colorectal surgery. Inflammatory bowel disease (IBD) is responsible of chronic inflammation and abnormal basal CRP that could influence the interest of its management after abdominal surgery.
The aim of this study was to evaluate CRP as an indicator of postoperative complication in a specific IBD population.

Methods
Retrospective study of patients undergoing ileocolic resection or ileal pouch-anal anastomosis for IBD between, 2012 and 2019.
Intra-abdominal complication was defined as any intra-abdominal event, infectious or otherwise, occurring during the immediate postoperative period.
The early postoperative period was defined as post-operative days (POD), 1 and, 2 and late postoperative period as POD, 3 and 4.

Results
Ileocolic resection represented, 242 patients and ileal pouch-anal anastomosis, 105 patients.
Intra-abdominal complications occured in, 18.1% of patients (ICR=40, 16.5% and IPAA=23, 21.9%).
Pre-operative CRP (48 hours before surgery) was available for, 96 patients (29.8%). Among them, 64 had an abnormal CRP value (median:, 13±45.4). No relation was found between a preoperative abnormal CRP value and post-operative intra-abdominal complications.
CRP was significantly higher at an early (105.2±56.0 vs, 128.1±69.8; p=0.008) and late stage (112.9±72.8 vs, 185.3±111.5; p &lt;, 0.0001) for patients having an intra-abdominal complication.
The best sensitivity and specificity values were obtained at POD, 3–4 with a CRP cut-off of, 75 with an area under the curve of, 0.71. The ability to rule out an intra-abdominal complication with a CRP Value &lt;75 mg/L was good with, at POD, 1–2 NPV=86.4% and PPV=19.9% and, at POD, 3 an NPV=90.3% and PPV=22.2%.
A BMI &gt;25kg/m2 (p=0.04) and an open surgical approach (p=0.009) were associated with higher CRP levels in the first POD.
In multivariate analysis, pre-operative steroid use (p=0.03), CRP at POD, 3 &gt;, 100mg/L (p=0.002) and a rise between CRP values more than, 50 mg/L (p=0.005) or, 100 mg/L (p &lt;, 0.0001) at, 48 hours were significantly associated with intra-abdominal complication. A CRP at POD, 1 &lt;75mg/L was associated with a lower rate of intra-abdominal complication (p=0.01).
A score using these, 4 independent factors was created and showed significant differences in intra-abdominal complication, anastomotic leakage and readmission rate.

Conclusion
CRP is a useful predictive marker to detect abdominal complication after surgery in IBD population. Measurement of CRP can help to reduce hospitalization stay and orientate towards complementary examinations.
P422 How achievable are the STRIDE-II treatment targets in real-world practise and do they affect outcome?
Authors: Routledge E , Meade S , Sharma E , Zeki S , Ray S , Anderson S , Sanderson J , Mawdsley J , Samaan M 
Published: January 2022

Abstract

Background
The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative provides recommendations on treatment targets for patients with Crohn’s disease (CD). The Simple Endoscopic Score for CD (SES-CD) is a validated endoscopic score and STRIDE-II recommends its use in clinical practice. We aimed to assess whether the STRIDE-II endoscopic endpoints are achievable and whether the degree of mucosal healing (MH) affects long term outcomes.

Methods
This is a retrospective observational study from, 2015–2020. We included patients with CD who had a baseline and follow-up SES-CD score after biologic therapy initiation. Data was collected via electronic records. The primary outcome was treatment failure, defined as the need for: i) change of biological therapy ii) corticosteroid use iii) CD-related hospitalisation or iv) surgery. We compared rates of treatment failure with the degree of MH achieved. Patients were followed up until treatment failure or study end (Aug, 2021). Statistics were performed using GraphPad v9.1.0 Software.

Results
50 patients were included (Fig, 1). Table, 1 shows the baseline characteristics. The median time to interval colonoscopy was, 16.3 (11.2–21.3) months. The proportion of patients achieving STRIDE-II end-points were: SES-CD (28, 56%), absence of ulcers (25, 50%) and endoscopic response [50% reduction in SES-CD] (31, 62%). Combined remission (SES-CD and Harvey Bradshaw Index [HBI] &lt;5) occurred in, 25 cases (50%). Treatment failure occurred in, 13 (26%) patients: biologic switch (7/50, 14%), corticosteroids use (2/50, 4%), CD-related admission (5, 10%), or surgery (6, 12%). Median time to treatment failure was, 19 months.
Fig, 2 shows the cumulative risk of treatment failure according to the achievement, or otherwise, of STRIDE-II endoscopic targets. Additionally, we show outcomes for combined endoscopic and clinical remission (HBI&lt;5). Failure to achieve SES-CD or a, 50% improvement in SES-CD were the strongest predictors for treatment failure.

Conclusion
In real-world clinical practice, calculating SES-CD scores at serial endoscopies is feasible and STRIDE-II targets are achievable in a reasonable proportion of patients (50%). Furthermore, achieving these targets has favourable long-term, clinically relevant outcomes.