bluuebunny/crossref_metadata_2025_split huggingface dataset:
P487 Anti TNF induced psoariasiform skin eruptions are increasing in in the biosimilar era – a descriptive study of drug induced skin manifestations and their management
Authors: Nu K P , Stamp K , Shaji S 
Published: January 2023

Abstract

Background
Skin disorders as extra-intestinal manifestations of inflammatory bowel disease 9IBD) are well recognized. In addition, contribution of drugs used in IBD in development of skin cancers is now fully understood. However, there are increasing reports of drug induced immune skin disorders resulting from or contributed by anti TNF agents. We aim to describe the etiology, manifestations and therapeutic approaches of anti TNF induced skin eruptions from a large tertiary center cohort.

Methods
A prospective database of IBD patients receiving biologics for IBD was interrogated for those who developed skin eruptions following initiation of anti-TNF therapy. We excluded patients who had pre-existing skin manifestations. All patients had dermatological expert review and confirmation of diagnosis as drug induced skin disorder. We collected their disease characteristics, time interval from initiation of biologics to development of skin disorder, the putative causative agent and the treatment of the skin lesions

Results
Sixty-eight patients (median age= 30 years, Female 44, male 24) among 1478 patients who received at least one dose of biologics developed a drug induced immune skin disorder. Median duration to development of skin lesions was 7.5 months. Anti TNF agents were responsible for 88.5% of the skin lesions with the commonest lesions being psoriasiform lesions in 34 (50%) patients. In our cohort, the psoriasiform lesions were more prevalent in patients who used biosimilar anti-TNF agents compared to the originator agent (31 vs 3). Forty patients required cessation of anti TNF agents because of skin eruptions. Twenty-eight of these were switched to ustekinumab with resolution of skin eruptions in 27 patients.

Conclusion
Anti TNF induced psoariasiform skin lesions appear to be more prevalent in the biosimilar era. Half of these patients will need treatment switch; ustekinumab appears to be an effective option in these patients
P495 Vedolizumab trough concentrations and histological remission in Ulcerative Colitis: Results from the LOVE-UC study
Authors: Hanzel J , Baert F , Löwenberg M , Ferrante M , Bossuyt P , Hoentjen F , Franchimont D , Palatka K , Peeters H , Mookhoek A , de Hertogh G , Clasquin E , Vermeire S , D'Haens G 
Published: January 2023

Abstract

Background
To date, the association between vedolizumab (VDZ) serum concentrations and histological remission in ulcerative colitis (UC) has not been studied prospectively. VDZ serum concentrations could potentially offer additional guidance for predicting histological remission. We studied the relationship between VDZ serum concentrations and histological remission in a prospective study.

Methods
LOVE-UC was a multicentre international (Belgium, the Netherlands, and Hungary) open label prospective study in patients with moderately to severely active UC treated with VDZ. VDZ serum concentrations were measured at trough prior to every infusion. Endoscopy was performed at baseline, week 26 and 52. Biopsies from the most severely affected area and endoscopy videos were scored by blinded central readers. Histological remission was defined as a Robarts Histopathology Index &lt;3 without neutrophils. Patients who did not undergo histological assessment were regarded as not having reached histological remission. Endoscopic remission was defined as a Mayo endoscopic sub-score 0.

Results
A total of 121 patients (61 male, 62 with prior exposure to tumour necrosis factor antagonists, mean total Mayo score at baseline of 9) received at least one infusion of VDZ. At week 26, 37.2% (45/121) patients were in histological remission, 38.8% (47/121) were in histological remission at week 52. The corresponding rates of combined histological and endoscopic remission were 19.8% (24/121) and 20.7% (25/121), respectively. Median VDZ serum concentrations were numerically higher at all time points in patients who achieved histological remission at week 26 than in those who did not (Table 1). Concentration thresholds (sensitivity, specificity, positive predictive value, negative predictive value, area under the receiver operating characteristic curve) of 32.5 mg/L (66%, 68%, 54%, 74%, 0.681) at week 6 and 12.5 mg/L (76%, 60%, 61%, 70%, 0.724) at week 22 were associated with histological remission at week 26. Higher proportions of patients achieved histological remission at week 26 in higher VDZ serum concentration quartiles (Figure 1).

Conclusion
VDZ serum concentrations were positively associated with histological remission in UC, although the predictive value of serum concentrations for subsequent histological remission was modest.
P503 The risk of mild, moderate and severe infections in IBD patients: results from a prospective, multicentre, observational cohort study – PRIQ
Authors: Rezazadeh Ardabili A , van Esser D , Wintjens D , Cilissen M , Deben D , Mujagic Z , Russ F , Stassen L , van Bodegraven A , Wong D , Winkens B , Jonkers D , Romberg-Camps M , Pierik M 
Published: January 2023

Abstract

Background
Immunomodulators and biologicals are essential in current IBD management, but are associated with increased risk of infections. Considering the growing number of treatment options, the benefit-risk balance of drugs is becoming increasingly important in clinical decision making. To date, post-marketing surveillance studies mainly focus on severe infections. As a result, data on mild and moderate infections are scarce. These infections take longer to clear in immunosuppressed patients and can substantially impact quality of life. We aimed to assess the incidence of all infections and identify risk factors for the development of infections in IBD patients.

Methods
We previously developed and validated a Patient-Reported Infections Questionnaire (PRIQ), with excellent diagnostic accuracy, covering 15 infection categories with a 3-month recall period. The current prospective, multicentre, observational cohort study was performed between Jun, 1 2020 and Jul, 1 2021, enrolling consecutive IBD patients using the PRIQ implemented in myIBDcoach, an established telemedicine platform. Infection severity was defined as mild (self-limiting or topical treatment), moderate (oral antibiotics, antivirals or antifungals) or severe (hospitalization or IV treatment). Incidence rates (IR) were calculated for all infections, stratified for severity and subtype. Risk factors for infections were identified using multivariable logistic regression.

Results
In total, 629 IBD patients were included which completed 2391 PRIQs during 572 person-years (PY) of follow-up, resulting in 990 reported infections, corresponding to IRs of 17.3, 11.8, 5.1, and 0.4 per 10PY for all, mild, moderate, and severe infections, respectively (Tables 1-2). Upper respiratory tract (IR 26.9/100PY) and urinary tract infections (IR 14.8/100PY) were the most commonly reported mild and moderate infections (Table 3). Compared to patients without treatment, patients on immunosuppressives more frequently experienced infections of any severity (mild: IR ratio (IRR) 1.57 [95%CI 1.21-2.06] p&lt;0.001, moderate: IRR 1.42 [95%CI 1.20-1.69] p&lt;0.001). On multivariable logistic regression, female sex (mild aOR 1.96; moderate aOR 1.71), smoking status (mild aOR 1.66; moderate aOR 1.86), higher BMI (moderate aOR 1.05), and more comorbidities (mild aOR 2.41; moderate aOR 1.82) were all significantly associated with the development of mild and moderate infections (Table 4).

Conclusion
In this real-world prospective study, immune suppressive therapy was associated with mild and moderate infections of any kind in IBD patients. These infections particularly occur in females, smokers, patients with higher BMI and more comorbidities. This information should be considered in personalised treatment selection.
P513 Prospective study on patients’ satisfaction and impact on quality of life of corticosteroid therapy in patients with Inflammatory Bowel Disease
Authors: Navarro Llavat M , García-Bosch O , Castro-Poceiro J , Bargalló García A , Ruiz Arroyo D , Navas Bravo Y , Erice Muñoz E , Barquero Declara D , Mata Bilbao A , Martín Llahí M , Ariza Solé X , Hernández Ballesteros C , Juan Juan A , Bustamante Robles K , Berbel Comas C , Blasco Pelicano A , Albareda Riera M , Domènech Morral E 
Published: January 2023

Abstract

Background
Corticosteroids (Cs) remain the first-line therapy for moderate-to-severe flares in patients with inflammatory bowel disease (IBD), both Crohn’s disease (CD) and ulcerative colitis (UC). On the other hand, their use has been associated to multiple adverse events (AEs) in randomized controlled trials and registries. Nevertheless, recent studies have repeatedly observed that the use of Cs has not decreased in spite of the increasing availability of biological agents and new small molecules licensed for IBD. The impact of Cs therapy on patients’ quality of life (QoL) and the patients’ perception on Cs have not been properly assessed in IBD. The purpose of this study was to assess the impact of a standard Cs course on the patients’ QoL and their satisfaction with treatment.

Methods
A prospective, longitudinal and observational study was conducted in adult IBD. All subjects received the same standard Cs regimen: starting dose of 1mg/kg/day (maximum 60mg/day) and tapering after 14 days with 10mg per week until reach 20mg/day, thereafter reduction was 5mg per week. QoL was assessed by the IBDQ-9 questionnaire at baseline, week 4 and at the end of Cs. Treatment satisfaction was assessed by the TSQM1.4 questionnaire at week 4 and at the end of Cs.

Results
Sixty-three patients were included in the study (54% CD and 43% UC; mean age 38.5±14.9 years; 46%females). Cs therapy failed in 41% of cases (active disease upon Cs discontinuation or need for rescue therapy). AEs attributable to Cs were reported in 84.1%, the most frequent were dermatologic (acne and moon face) (60.3%), hypokalemia (44.8%) and poor quality of sleep (40%). Serious AEs were reported in 20,6%, mostly mild or moderate infections that resolved without sequelae. IBDQ-9 scores increased 12.4 and 13.5 points at 4 weeks and at the end of Cs, respectively (p&lt;0.05). Improvement in QoL was not associated with any of the analysed factors (gender, age, type of IBD, response to treatment and AEs). The overall degree of satisfaction with Cs was 68.5 over 100 points, with the highest score related to satisfaction with adverse events (82/100). Satisfaction with treatment was only associated with the achievement of clinical remission or development of steroid dependence.

Conclusion
A standard Cs course significantly increases the QoL of patients with IBD. Furthermore, a high satisfaction with treatment was perceived by patients.
P517 Ustekinumab monitoring levels predict the need for intensification in patients with inflammatory bowel disease.
Authors: Ramos Lopez L , Ramos-Díaz R , Alonso-Abreu I , Mourani-Padron I , Carrillo-Palau M , Reygosa M C , Medina-Chico S , Gutierrez-Nicolas F , Nazco-Casariego G J , Hernandez-Guerra M 
Published: January 2023

Abstract

Background
Therapeutic drug monitoring (TDM) is a valuable tool to optimize anti-TNF biologics in inflammatory bowel disease (IBD). However, for the non-anti-TNF agents (such as Ustekinumab-UST- an anti-IL12/23) TDM value and evidence in real-world IBD patients is scarce although emerging data suggest that higher drug concentration (&gt;4.5 µg/ml) of these biologics agents predicts better clinical outcomes. We evaluated associations between UST levels and clinical outcomes in real-world IBD patients.

Methods
A cross-sectional study was performed in IBD patients who received maintenance therapy (≥16 weeks) with UST and followed in our IBD unit between June 2020 and May 2021. UST trough concentration was assessed at the time of inclusion and clinical outcome were reviewed by starting UST use (PRE), at the time of blood extraction (inclusion-EXT), and after 6 months of follow-up (POST). Clinical response was determined by Harvey-Bradshaw Index (HBI) (clinical remission; HBI≤4 points or pMayo ≤2 points) and biochemical response by fecal calprotectin (FC) (biochemical response CF&gt;50 % reduction from basal value and biochemical remission CF &lt;150 g/kg). The need for surgery, intensification, or change of treatment at the end of the follow-up was registered.

Results
A total of 62 patients (53.2% male; mean age 46 (41-50) years; Crohn’s disease n=57/ ulcerative colitis n=3/indeterminate colitis n=2) were included. The time from diagnosis to initiation of UST treatment was 149 (122-176) months. 35.5% of patients received co-treatment with immunosuppressors and 95,6% had received previous biologic agents (15,6% more than 2 previous biologics). The mean time of UST use was 13 (10-16) months. The mean UST level was established at 7.1 µg/ml (SD 4.3) with higher levels in intensified patients (UST every 4 weeks; n=17) at the time of extraction (9.4 µg/ml (4.3) vs. 6.2 µg/ml (4.0); p= 0.03). However, no differences were found in UST levels between patients achieving clinical remission (n=52,83.9%)) compared to non-responders (7.2 µg/ml (4.4) vs. 6.7 µg/ml (4.4), respectively; p=0. 71); nor in those achieving biological remission at 6 months (n= 31, 56.4%)) compared to non-responders ((7.0 µg/ml (4) vs 6.6 µg/ml (4.5), respectively; p= 0.7). Only 2 patients discontinued UST treatment and 7 patients needed to intensify treatment every 4 weeks during follow-up. In logistic regression analysis, the UST level lower than 4.5 µg/ml showed an independent predictive value for the need for UST intensification in the subsequent 6 months (OR 5.7, 95% CI 1.01-32.9).

Conclusion
UST is an effective drug for achieving clinical and biological remission in patients with IBD. UST level (&lt;4.5 µg/ml ) may guide the need for treatment intensification at 6 months.
P519 Mirikizumab pharmacokinetics and exposure-response relationships in patients with moderately to severely active ulcerative colitis: results from randomised phase 2 and phase 3 induction and maintenance trials
Authors: Friedrich S , Chua L , Zhang X C 
Published: January 2023

Abstract

Background
Mirikizumab (MIRI) is a p19-targeted anti–interleukin-23 developed for ulcerative colitis (UC), and has demonstrated efficacy in Phase 2 (AMAC, NCT02589665) and Phase 3 (LUCENT-1, NCT03518086; LUCENT-2, NCT03524092) trials in patients with moderately to severely active UC. We characterised MIRI pharmacokinetics (PK) and the exposure-response (E-R) relationship between MIRI exposure and clinical outcomes in these 3 trials.

Methods
Patients received 12-week MIRI induction (50, 200 or 600 mg [AMAC] or 300 mg [LUCENT-1] intravenous [IV] every 4 weeks [Q4W]), and induction responders then received MIRI maintenance (200 mg subcutaneous [SC] Q4W or every 12 weeks for 92 weeks in AMAC; 200 mg SC Q4W for 40 weeks in LUCENT-2). Serum PK parameters were analysed by non-linear mixed-effects modelling, and covariate effects on MIRI exposure were evaluated using simulation-based estimations. Relationships between MIRI exposure and clinical remission, clinical response, endoscopic remission and symptomatic remission, based on the Mayo scoring system, were assessed using logistic regression models.

Results
MIRI PK (clearance, 0.022 L/hr (95% CI 0.02,0.03); volume of distribution for central and peripheral compartments, 3.11 L (95% CI 3.07, 3.15) and 1.69 L (95% CI 1.03, 2.57); half-life, 9.5 days) were best described by a 2-compartment model with first-order absorption. Clearance increased with body weight and decreased with albumin concentration, and bioavailability decreased with body mass index, but impacts of covariates were small relative to random variability. MIRI SC bioavailability was 48%. Modelling of E-R relationships during MIRI induction in AMAC revealed statistically significant positive associations of MIRI exposure with clinical response and with change in Modified Mayo Score. Maximum effect was predicted at 300 mg, with no significant improvement at higher doses. Steep positive relationships between exposure and efficacy in LUCENT-1 were not explained by patient covariates, and analyses suggest confounding by unknown variables. MIRI exposure during maintenance was not a significant predictor of efficacy in AMAC and LUCENT-2.

Conclusion
MIRI PK characteristics were typical of an immunoglobulin G monoclonal antibody. The MIRI E-R relationship revealed an apparent lack of sensitivity of efficacy to individual patient exposures at the dose levels studied in Phase 3. Overall, the PK and E-R data suggest that dose adjustments due to patient factors are not justified.
P522 Kono-S anastomosis reduces endoscopic and surgical post-operative recurrence in Crohn’s disease. The SuPREMe-CD Trial Update.
Authors: Luglio G , Rispo A , Tropeano F P , Giglio M C , Cricrì M , Imperatore N , De Sire R , Guarino A D , Bucci L , Castiglione F , De Palma G D 
Published: January 2023

Abstract

Background
Recently, a new antimesenteric, functional, end-to-end, hand-sewn ileocolic anastomosis (Kono-S) has shown a significant reduction in endoscopic recurrence (ER) and surgical recurrence (SR) rate in Crohn’s disease (CD). This trial aimed to provide randomized controlled data comparing Kono-S anastomosis and conventional stapled ileocolic side-to-side anastomosis.

Methods
Randomized controlled trial (RCT) at a tertiary referral centre. The primary endpoint is ER rate (Rutgeerts score ≥ i2) after 6 months and surgical recurrence at 60 months. Secondary endpoints are clinical recurrence (CR) rate after 24 and 36 months, and SR after 24 and 36 months. Statistics was performed by using standard analyses. Furthermore, a sample size able to consent the detection of a reduction &gt;30% in total endoscopic recurrence (when assuming a 60% to 65% ER expected rate in the control group and a 30% in the case group) was calculated; to allow a 10% drop-out of patients, 36 patients per group were needed (72 patients in the entire population).

Results
A total of 119 CD patients were included in the study. In all, 51 ileocolic CD patients were randomized in the Kono group and 68 in the conventional side-to-side group.
At 6 months, 17 (33.3%) patients in the Kono group and 51 (75%) patients in the conventional group presented an ER (Rutgeerts score≥i2) at colonoscopy (p&lt;0.001). A severe post-operative ER (Rutgeerts score≥i3) was found in 8 (15.7%) patients in the Kono group versus 23 (33.8%) patients in the conventional group (p=0.03).
At 24 months, CR rate was 19.6% in the Kono group versus 30.9% in the conventional group (p=0.2), while SR rate was 0% in the Kono group versus 4.4% (3 patients) in the standard group (p=0.2).
At 36 months, CR rate was 19.6% in the Kono-s group versus 33.8% in the conventional group (p=0.1). At 36 months, no patients (0%) in the Kono group experienced SR, while 6 patients (8.8%) in the conventional group did (p=0.03).
Furthermore, when considering a median follow-up of 54 (42-60) months at interim analysis of SR, the difference between the two groups was confirmed to be significant (0% vs 8.8%; p=0.02).

Conclusion
This is the first RCT comparing Kono-S anastomosis and conventional side-to-side anastomosis in CD. The results demonstrate a significant reduction in postoperative endoscopic and surgical recurrence rates, no safety issues, and a favourable trend for lower clinical recurrence rate in patients who underwent Kono-S anastomosis compared to the conventional side-to-side anastomosis.
P525 Real-world effectiveness and safety of ustekinumab in patients with ulcerative colitis: a systematic review and meta-analysis
Authors: Taxonera C , Olivares D , Olga N L G , Alba C 
Published: January 2023

Abstract

Background
Knowledge of the real-world effectiveness and safety of tofacitinib for ulcerative colitis (UC) is relevant to confirm the benefit observed in clinical trials. The aim of this systematic review was to summarize reported evidence on the real-world outcomes of ustekinumab for UC and to conduct a meta-analysis of effectiveness and safety data.

Methods
A systematic search was conducted in electronic databases PubMed, Web of Science, EMBASE, and Science Direct, and conference proceedings until 15 September 2022 for real-world studies evaluating ustekinumab for UC. A random-effects meta-analysis model was used to calculate the pooled rates of clinical and safety outcomes. We evaluated the outcomes at week 8, week 12 to 16, month 6, and month 12. Need for colectomy and adverse events (AE) were reported as percentages and incidence rates (IRs) per 100 patients-year (PY) of exposure.

Results
Of the 254 citations identified, 19 studies were included with 3786 patients. Sixteen studies reported prior exposure to biologics or JAK inhibitors and included 1003 patients, of whom 92.3% were previously treated with any biologic, 61.1% with both anti-TNF and vedolizumab, and 16.4% with any biologic and tofacitinib (Figure 1). Remission was achieved in 45.4% of patients at week 8 (95% confidence interval 30.1-60.6%), 43.8% (38.4-49.2%) at weeks 12 to 16, 44.6% (35.9-53.3%) at month 6, and 50.6% (36.3-64.8%) at month 12 (Figure 2). Response was achieved in 61.2%, 59.4%, 65.2%, and 76.8% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively (Figure 3). Corticosteroid-free remission was achieved in 18.7%, 36.8%, 34.5%, and 39% of patients at week 8, weeks 12 to 16, month 6, and month 12, respectively. Endoscopic improvement was achieved in 29.9%, 24.3% %, and 58.2% of patients at weeks 12 to 16, month 6, and month 12, respectively. Almost 30% of the patients needed dose escalation, which was effective in 40% of these patients. The pooled rate of persistence with ustekinumab was 76.9% and 73.3% at month 9 and month 12, respectively. The IRs of colectomy, AE, serious AE, and serious infections were 5.1, 7.9, 1 and 0.5 per 100 PY, respectively (Figure 4).

Conclusion
The results of this systematic review and meta-analysis of real-world studies confirm the effectiveness of ustekinumab in a highly treatment-refractory population of patients with active moderate-to-severe UC. The acceptable safety data presented here support the positive long-term benefit-risk profile of ustekinumab in the treatment of UC. These real-world effectiveness and safety results were consistent with clinical trials and provide a broader perspective that can be used to aid treatment decisions in a more heterogeneous clinical setting.