bluuebunny/crossref_metadata_2025_split huggingface dataset:
P522 Prior pharmacotherapy patterns among patients with IBD in the USA initiating biologic therapy
Authors: Bornheimer R , Hass S , NAG A , Oster G 
Published: January 2020

Abstract

Background
Treatment for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]) has shifted from symptom management using corticosteroids to targeted therapies such as tumour necrosis factor (TNF) inhibitors. An increase in therapeutic options warrants a better understanding of current treatment pathways. This study reports on the pharmacotherapy history of patients with CD and UC prior to initiation of an IBD-targeted biologic.

Methods
Using the US IQVIA™ Real-World Data Adjudicated Claims Database, we identified adults (≥18 years) with CD or UC who initiated biologics indicated for these diseases from 1 January 2016 to 30 June 2017. Patients were stratified based on the most recent biologic received; the date of initiation was designated the index date. Patients with &lt; 12 months of continuous medical coverage prior to the index date were excluded. Patterns of prior IBD-related pharmacotherapy, in terms of the number and type of biologics, and time spent receiving the biologic, were examined in relation to the index biologic for the study period 1 January 2011 to 30 June 2017.

Results
In total, 3010 patients with UC and 5210 with CD were identified. Among patients with UC, 1285, 977, 587 and 161 initiated treatment with adalimumab, infliximab, vedolizumab and golimumab, respectively. Among patients with CD, 2634, 1436, 737, 241 and 162 began treatment with adalimumab, infliximab, vedolizumab, certolizumab and ustekinumab, respectively. Most patients beginning treatment with infliximab or adalimumab were biologic-naïve (UC: 79.9%, 89.3%, respectively; CD: 77.8%, 84.6%, respectively). Patients starting treatment with other biologics, however, had typically received at least one IBD-related biologic previously (Figure 1). Among patients who were not biologic-naïve at initiation of therapy, the mean total duration of prior biologic exposure was 17.8 months and 26.6 months for patients with UC and CD, respectively.

Conclusion
During the study period, anti-TNFs were the most commonly initiated biologics in both groups of patients. Although newer IBD-related biologics (i.e. vedolizumab and ustekinumab) are typically preceded by treatment with other biologics, most patients receiving an anti-TNF are biologic-naïve.
P537 Real-world long-term effectiveness of ustekinumab in Crohn’s disease: Results from the ENEIDA registry
Authors: Iborra Colomino M I , Beltrán B , Fernández-Clotet A , Iglesias Flores E , Navarro P , Rivero M , Gutiérrez A , Sierra-Ausin M , Mesonero F , Ferreiro-Iglesias R , Hinojosa J , Calvet X , Sicilia B , González-Muñoza C , Antolín B , González Vivo M , Carbajo A Y , García S , Martín-Cardona A , Surís Marín G , Martín-Arranz M D , De Francisco R , Cañete F , Carlos T , Gomollón F , Lorente R , Rodríguez-Lago I , Forés-Bosch A , Bernardos E , Ramos L , Delgado P , Hernández A , Van Domselaar M , Hervás D , Domènech E , Nos P 
Published: January 2020

Abstract

Background
There are limited data of long-term ustekinumab administered according to the doses recommended in the UNITI studies. The objective of this study was to assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn’s disease (CD) (LONG-CROHNUSK Study).

Methods
Multicentre study of CD patients starting ustekinumab at the recommended dose based on weight ~6 mg/kg IV week 0, 90 mg SC week 8 and maintenance 90 mg SC every 8 or 12 weeks and with 1 year of follow-up. Values for Harvey-Bradshaw Index (HBI), endoscopic activity, C reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs), surgeries and hospitalisations were documented. Potential predictors of clinical and endoscopic remission were examined.

Results
Four hundred and seven patients were analysed (Table 1). For the maintenance dose, ustekinumab 90 mg was administered SC every 12, 8 and 4 weeks in 56 (14%), 318 (84.5%) and 7 (1.5%) patients, respectively. An interval reduction was applied for 118 patients (29%). Before 52 weeks, treatment discontinuation occurred in 71 patients (17%). At baseline, 295 (72%) had an HBI &gt;4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal (&lt;250 μg/g) in the 44% and 54% of the patients at weeks 26 and 52, respectively. CRP returned to normal (&lt;3 mg/l) in 36% and 37% of the patients at weeks 26 and 52 respectively. HBI, FC, and CRP values over time are shown in Figure 1. Of the 159 patients with endoscopy at 52 weeks, 25 (16%) were in remission and 58 (36%) presented mild activity. Thirty-eight (9.3%) patients worsened extra-intestinal manifestations and 33 (8%) their perianal disease. AEs were recorded in 54 patients, 73 were hospitalised and 53 had surgery. An association was shown for fewer previous anti-TNF agents and ileal localisation with clinical remission, and for endoscopic severity at baseline with poor response. No factors correlated with endoscopic remission.

Conclusion
This is the first study to show the real-world long-term effectiveness, endoscopic improvement and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.
P566 Assessing the efficacy of biologics in ulcerative colitis: A real-life, observational retrospective multicenter study using the propensity score analysis: The ‘A.U.R.O.R.A.’ comparison study
Authors: Cassinotti A , Mezzina N , Di Paolo D , Lenti M V , Bezzio C , Stradella D , Mauri M , Zadro V , Cortellezzi C , Ricci C , Casini V , Radice E , Massari A , Ardizzone S , Pastorelli L , Di Sabatino A , Manes G , Caprioli F , Vecchi M , Tari R , Occhipinti P , Fichera M , Invernizzi P , Parravicini M , Segato S , Pace F , Testoni P A , Tinelli C , De Silvestri A 
Published: January 2020

Abstract

Background
Until 2014, infliximab originator (Remicade, IFX-O) was the only biological treatment approved in Italy for ulcerative colitis (UC), followed by the sequential approval of adalimumab (ADA), infliximab biosimilar (CTP-13), golimumab (GOL) and vedolizumab (VDZ). Recently, comparative trials among these drugs provided conflicting results on their reciprocal superiority or equivalence.

Methods
In a retrospective, real-life, multicenter inception cohort study involving 11 Italian IBD tertiary centres, all consecutive patients with moderate-to-severe active UC, treated with ADA, CTP-13, GOL or VDZ after their post-marketing approval (2014–2018) were followed-up for 1 year or until relapse. All drugs were compared with each other and to patients treated with Remicade in 2013–2014 (reference group). The 80% power calculation of the study required at least 75 patients in each arm. A propensity score analysis was performed. The primary endpoint was the 1 year relapse-free, optimisation-free, steroid-free remission, defined as Mayo partial score ≤2, with bleeding subscore = 0, no relapse after first clinical remission and no optimisation with dose intensification or steroids courses. Multiple further secondary endpoints were analysed (Table 1).

Results
492 patients (ADA=90, CTP-13=105, GOL=79, VDZ=142, IFX-O=76) were included. Overall, 65% achieved clinical remission once during the follow-up, with IFX-O performing better than GOL and VDZ. The relapse rate was 24%, with the lowest rates with VDZ. The primary end-point was achieved in similar percentages in all groups, except for lower rates with GOL than IFX-O. IFX-O performed better than each other drug for other clinical outcomes (Table 1). Discontinuation for intolerance was similar among the drugs, but CTP-13 had more frequent adverse events (mainly infusion reactions) than ADA, VDZ and IFX-O.

Conclusion
Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year, except for GOL vs. IFX originator. IFX-O appears more effective in multiple questionable clinical outcomes. IFX biosimilar had more adverse events than the other drugs. IFX originator should be used as the reference drug in head to head, controlled, comparison trials for current and future biologics in UC.
P568 An open-label, multicenter, phase ib, pharmacokinetic (pk) and safety study of a fimh blocker, Sibofimloc (TAK-018/EB8018), in patients with Crohn’s disease (CD)
Authors: Reinisch W , Hébuterne X , Buisson A , Schreiber S , Desreumaux P , Paillarse J M , Bonny C 
Published: January 2020

Abstract

Background
Sibofimloc (EB8018/TAK-018) is a gut-restricted orally administered, first-in-class, FimH blocker that targets FimH, a TLR4 receptor, expressed on E. coli and other Enterobacteriaceae in patients with CD. In a previous study, sibofimloc up to 1500 mg twice daily was well tolerated when administered to healthy subjects over a 14-day period. PK results indicated that sibofimloc was detectable in plasma at a very low level. The current study investigated the PK, safety, and pharmacodynamic effects of sibofimloc following 13 days of 1500 mg twice daily oral administration in patients with CD. Objectives of this study were to determine the PK (primary) and safety profiles, effects on inflammatory biomarkers, gut microbiome and on stool frequency and pain score.

Methods
We conducted a multicenter open-label study to enrol 8 adult patients with active CD (faecal calprotectin (FCP) ≥150 µg/g and/or ulcers at colonoscopy). Pregnant women were excluded. This study was divided into two parts. 1)Two patients received a single dose of 3000 mg sibofimloc followed, after a wash-out period, by a 13 day-period with1500 mg twice daily. 2)After review of data from these two patients, the 6 remaining patients received 1500 mg sibofimloc twice daily for a 13 day period.

Results
Cmax values for the 2 initial patients (after single dose 3000 mg sibofimloc) were 51.3 and 348 ng/ml respectively and allowed part 2 of the study. The main safety and PK data of an interim analysis after the first 4 patients had been treated with sibofimloc 1500 mg twice daily are presented in the table.
In a previous study in 7 healthy subjects, after 14 days sibofimloc 1500 mg twice daily, median Cmax[min-max] at Day14 was 49[19.2–86.6]ng/ml.

Conclusion
These preliminary data confirmed that sibofimloc was well tolerated. In the small subset of patients analyzed, there was a slightly higher plasma exposure and interpatient variability compared with what has been seen earlier in healthy subjects. The safety and PK data allowed the continuation of the clinical development program with the initiation of a phase 2 trial for postoperative maintenance in patients with CD.
P574 Incidence and indicators of suboptimal response to tumour necrosis factor antagonist therapy in Chinese patients with inflammatory bowel disease: Results from the EXPLORE study
Authors: Li J , Li Z , Hu P , Wen Z , Cao Q , Zou X , Chen Y , Wang Y , Zhong J , Shen X , Demuth D , Fedeeva O , Xie L , Chen J , Qian J 
Published: January 2020

Abstract

Background
Inflammatory bowel disease (IBD) patients may experience a suboptimal response to anti-tumour necrosis factor (TNF) therapy. In China, these data are limited. The EXPLORE study aimed to assess the incidence and indicators of suboptimal response to first-line anti-TNF agents in IBD patients in real-world practice in the newly industrialised countries.

Methods
The EXPLORE study was a multinational, retrospective chart review study. In the China subgroup, adult patients from 10 centres diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) and who initiated first anti-TNF treatment between March 2010 and March 2015, were included. The cumulative incidence (CI) of suboptimal response was assessed over 24 months since the anti-TNF initiation. The indicators of suboptimal response included: IBD-related hospitalisation, dose-escalation, discontinuation including switch to another anti-TNF, non-biologic therapy augmentation, or IBD-related surgery. Primary non-response (PNR) and secondary loss of response (SLOR) were defined as any suboptimal response indicator at &lt;4 and ≥4 months after anti-TNF initiation, respectively.

Results
Overall, 287 first-line anti-TNF treated patients (35 UC; 252 CD) were included: male, UC 54.3% (n = 19), CD 74.6% (n = 188); mean (SD) age (years), UC 43.1 (14.2), CD 31.9 (11.3); median (min-max) disease duration (years), UC 1.0 (0–9), CD &lt;1 year (0–21); median (min-max) follow-up (months), UC 27.6 (24–60), CD 40.0 (24–60). At 12 and 24 months, the CI of suboptimal response to first anti-TNF treatment was 51.4% and 75.7% in UC, 45.4% and 57.0% in CD, respectively (Figure 1). The median time to the first suboptimal response was 7.2 months in UC and 14.3 months in CD. The CI of PNR was 31.2% in UC and 33.7% in CD. The CI of SLOR was 29.4% and 64.7% in UC, 17.7% and 35.2% in CD at 12 and 24 months, respectively. The most frequent first suboptimal response indicator was ‘discontinuation of anti-TNF therapy’ in UC patients (56.3%) while for CD patients it was ‘IBD-related hospitalisation’ (56.1%) followed by ‘augmentation with non-biological therapy’ in both cohorts (UC 31.3%; CD 22.8%).

Conclusion
Approximately three-quarters of UC and over half of CD patients experienced a suboptimal response to their first anti-TNF agent at 24 months. Given the high unmet needs observed with anti-TNF therapies in China, IBD patients may benefit from greater optimisation of care and new biologic options.
P611 Provision of care for pregnant women with IBD in the UK - the current landscape
Authors: Moore E , Wolloff S , Glanville T , Selinger C P 
Published: January 2020

Abstract

Background
inflammatory bowel disease (IBD) results in increased rates of negative pregnancy outcomes; particularly in poorly controlled disease. We aimed to describe the current landscape of provision of antenatal care for women with IBD in the UK.

Methods
This cross-sectional study collected data on service set-up, on principles of care pre, during, and after pregnancy and on perceived responsibilities of clinicians. An online survey was distributed to all gastroenterology units in the UK.

Results
Data were provided for 97 of 273 IBD units. Pre-pregnancy counselling was not available in 7%, offered routinely (39%), or on request (54%) but predominantly (91%) in an ad-hoc fashion rather than in a dedicated set-up. Ninety-two per cent of units provided a nominated gastroenterology consultant during pregnancy. In 86% of this was the patient’s usual consultant rather than a consultant with expertise in pregnancy (14%). Combined clinics with obstetricians and gastroenterologists were offered in 14% of units only, but more often in academic rather than district hospitals (24% vs. 7%; p = 0.043) Otherwise, communication with obstetrics was ‘as and when required’ in 51% of cases. Patients were reviewed either every trimester (55%), monthly (15%) or ‘only when required’ (30%). The majority of respondents thought gastroenterologists should be involved in decisions regarding routine vaccinations (70%), breastfeeding (80%), folic acid dosage (61%), and VTE prophylaxis (53%). Sixty-five per cent of participants thought that gastroenterologists should be involved in decision-making regarding the delivery method. Regarding IBD indications for elective caesarean section, 94% of participants recommended these for active peri-anal disease, 30% for previous but healed peri-anal disease, 56% for ileo-anal pouch and 20% for previous abdominal and/or pelvic surgery.

Conclusion
In a nationwide survey on the provision of antenatal IBD care we found considerable variation in all aspects of service provision, particularly the availability of expertise and specialist services. We have detected areas of poor care (review only when required, communication ad-hoc only, poor provision of dedicated pre-pregnancy counselling). A significant minority of IBD units also felt that they do not need to provide input into areas such as VTE prophylaxis, delivery method and folic acid dosing. IBD indications for caesarean section seem to be poorly understood by a sizable minority. A basic framework to inform service set-up, and better education on the available clinical guidance for clinicians, is required to ensure consistent identification and review of patients and high-quality care.
P613 Use of adalimumab biosimilar ABP 501 in Crohn’s disease: A real-life experience
Authors: Ribaldone D G , Vernero M , Pellicano R , Morino M , Saracco G M , Astegiano M 
Published: January 2020

Abstract

Background
The use of biologics in Crohn’s disease (CD) entails an increasing cost on national health systems. The use of biosimilars of adalimumab in CD is based on the concept of extrapolation of the results obtained in rheumatoid arthritis and in psoriasis, while no study about the efficacy and safety on CD of the biosimilars approved in Europe have been published. The aim of our study was to analyse, for the first time in literature, the effectiveness and safety of ABP 501 in CD patients naïve to adalimumab and its retention rate in CD patients who switched from adalimumab originator.

Methods
We performed an observational study on patients prospectively followed at the gastroenterology clinic of the Turin University Hospital. Inclusion criteria are (a) CD diagnosed according to ECCO criteria; (b) age ≥16 years; (c) initiation of therapy with ABP 501. Exclusion criterian is follow-up duration of less than 3 months for adalimumab-naïve patients, less than 6 months for patients who switched to ABP 501. Primary outcomes were (a) for patients treated with ABP 501 as first adalimumab: clinical response rate at 12 weeks and (b) for patients who switched to ABP 501: drug retention at 24 weeks. Secondary outcomes were (a) clinical remission rate at week 12 (for patients treated with ABP 501 as first adalimumab); (b) HBI and CRP reduction at week 12 (for patients treated with ABP 501 as first adalimumab), no significant change in HBI and CRP values at week 24 (for patients who switched to ABP 501); (c) analysis of predictors; and (d) adverse events incidence.

Results
Eighty-seven patients were included, of which 25 were naïve to adalimumab originator and 62 were switched to ABP 501. In adalimumab-naïve patients, the clinical response at 3 months was 60% (15/25), clinical remission at 3 months was 56% (14/25). At 6 months, 95.2% (59/62) of the patients switched to ABP 501 were still in therapy, without a significant increment of clinical activity (Harvey–Bradshaw Index from 3.4, 95% CI = 2.4 – 4.4, to 3.8, 95% CI = 2.7 – 4.9, p = 0.23), and inflammatory biomarker (CRP from 4.2 mg/l, 95% CI = 2.5 mg/l – 5.9 mg/l, to 3.6 mg/l, 95% CI = 2.2 mg/l – 5 mg/l, p = 0.32). No unexpected adverse events occurred during the study period.

Conclusion
Our results support ABP 501 as an efficacious and well-tolerated drug, at least in the short-term, and its interchangeability with its originator in the treatment of CD.
P637 PERFUSE: A french non-interventional cohort study of infliximab-naive and transitioned patients receiving infliximab biosimilar SB2; An interim analysis
Authors: Bouhnik Y , Fautrel B , Desjeux G , Freudensprung U , Brigui A , Addison J 
Published: January 2020

Abstract

Background
SB2 is approved in the EU as infliximab (IFX) biosimilar, having demonstrated bioequivalence and similar efficacy, safety and immunogenicity as the reference. Little evidence is published on real-world use of SB2 in patients who are either IFX-naïve, or transitioned from originator or another IFX biosimilar. PERFUSE is an ongoing non-interventional study of 1,374 patients receiving SB2 as routine therapy at 12 gastroenterology sites across France, with objectives to describe clinical characteristics, immunogenicity and SB2 persistence over 12 months.

Methods
Eligible adult patients are diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) and initiated SB2 in routine clinical practice after September 2017 as their first IFX or transitioning from treatment with reference IFX or another IFX biosimilar. Data are captured from routine patient records for up to 12 months (M12) following initiation. Outcome measures include persistence on SB2, clinical characteristics at baseline (time of initiation of SB2) and disease scores (Harvey–Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI)) and SB2 dose over time.

Results
This interim analysis (IA) includes 755 patients (580 with CD; 59 IFX-naïve, 521 transitioned from prior IFX: 175 with UC; 33 IFX-naïve, 142 transitioned from prior IFX). In the 663 patients with prior IFX, no clinically relevant difference in disease score from baseline to M12 was observed; mean individual change was −0.3 (95% CI −0.8, 0.1) and -0.2 (95% CI −0.6, 0.3) in the CD cohort transitioned from reference IFX (n = 157) and biosimilar IFX (n = 83), respectively; −0.3 (−1.1, 0.4) and 0.0 (-0.9, 0.9) in the UC cohort transitioned from reference IFX (n = 41) and biosimilar IFX (n = 26), respectively. Mean (95% CI) SB2 dose (mg/kg), was similarly unchanged from baseline to M12: 7.2 (5.0, 10.0) and 7.6 (5.0, 10.0) in patients with CD transitioned from reference IFX or from biosimilar IFX; 7.0 (5.0, 10.0) and 7.3 (5.0, 10.0), 7.5 (5.0, 10.0) and 7.7 (5.0, 10.0) in patients with UC transitioned from reference IFX or biosimilar IFX, respectively. By data extraction date (23 October 2019), 374 patients with CD and 105 with UC had reached M12; persistence on SB2 was 92.2% (95% CI 89.1, 94.7) and 90.5% (95% CI 83.2, 95.3) in CD and UC, respectively. Reasons for discontinuation (n) were: adverse event (9), primary loss of response (7), secondary loss of response (12) and unspecified (16).

Conclusion
This IA indicates that patients with IBD can be successfully and safely transitioned from reference or biosimilar IFX to SB2, with no loss of disease control and without need for dose escalation. Over 90% of transitioned patients continued SB2 treatment at M12 post-initiation.
P645 Adalimumab drug monitoring is superior to empirical treatment adjustment in inflammatory bowel disease
Authors: CURRAIS P , Fernandes S , Bernardo S , Correia L , Gonçalves A R , Baldaia C , Moura Santos P , Valente A , Tato Marinho R 
Published: January 2020

Abstract

Background
Anti-TNF blockers are effective drugs in the treatment of inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) of Adalimumab (ADA) may potentially improve clinical outcomes in this setting, but data are still scarce.

Methods
To compare ADA TDM and empirical treatment adjustment (ETA) in patients with IBD. Outcomes were evaluated at 2 years and included hospitalisation, surgery, treatment discontinuation, endoscopic remission and treatment failure (any unfavourable event).
Single-centre retrospective study, including patients under ADA therapy.

Results
103 patients were included, 86 with Crohn’s disease and 17 with ulcerative colitis. 52.4% male, mean age 28.5 (18–72). 56 patients received ADA TDM and 47 ETA. At 2-years, rates of treatment escalation (57.1% vs. 21.3%, p &lt;0.001), mucosal healing (69.6% vs. 48.9%, p =0.032) and treatment discontinuation (17.9% vs. 4.3%, p =0.032) favored the TDM group. For TDM and ETA respectively, there was no statistically significant difference regarding need for hospitalisation (12.5% vs. 21.3%, p = 0.232), surgery (5.4% vs. 14.9%, p =0.103) and treatment failure (26.7% vs. 34.5%, p =0.395).

Conclusion
Our results suggest a benefit of TDM in achieving higher rates of mucosal healing The higher rates of treatment discontinuation suggest that TDM improves drug selection as patients switched unhelpful treatment earlier.