bluuebunny/crossref_metadata_2025_split huggingface dataset:
P434 Effectiveness and safety of ustekinumab in ulcerative colitis: real-world evidence from Eneida Registry
Authors: Chaparro M , Garre A , Iborra M , Barreiro-de Acosta M , Casanova M J , De Castro L , Fernández-Clotet A , Hinojosa J , Boscá-Watts M , Busquets D , López-García A , Lorente R , Manceñido N , Martínez T , Monfort D , Pérez-Calle J L , Villoria A , Angueira T , Bermejo F , Carbajo A Y , Carpio D , González-Muñoza C , Gomollón F , Huguet J M , Rivero M , Iglesias-Flores E , Sierra M , Hernández-Villalba L , Domènech E , Gisbert J P 
Published: January 2020

Abstract

Background
Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life.

Methods
Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring.

Results
Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to &gt;2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant).

Conclusion
Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.
P445 Efficacy and safety of induction therapy with calcineurin inhibitors followed by maintenance therapy with vedolizumab in severe ulcerative colitis: a large patient cohort with long-term follow-up
Authors: OLLECH J , Dwadasi S , Normatov I , Israel A , Rai V , Sossenheimer P , Christensen B , Dalal S , Pekow J , Sakuraba A , Cohen R , Rubin D 
Published: January 2020

Abstract

Background
The options for the medical management of patients with severe ulcerative colitis failing IV steroids are limited and include the calcineurin inhibitors cyclosporin or tacrolimus, especially in patients who had previously failed anti-TNF agents. Following induction therapy with a calcineurin inhibitor, transitioning to vedolizumab as maintenance therapy could be an option. We report on the largest cohort of patients successfully induced with calcineurin inhibitors who were then transitioned to vedolizumab maintenance therapy.

Methods
We performed a retrospective observational study of adult ulcerative colitis patients followed at the University of Chicago Inflammatory Bowel Disease Center. Patients with severe steroid-refractory ulcerative colitis were included if they received a calcineurin inhibitor (ciclosporin or tacrolimus) as induction therapy followed by maintenance therapy with vedolizumab between January 2014 and December 2018. Patients who had a follow-up of fewer than three months were excluded. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14.

Results
A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with calcineurin inhibitors for severe steroid-refractory colitis. Truelove and Witts criteria for Acute Severe Ulcerative Colitis were fulfilled in 77% of patients, and 97% of patients had moderate to severe endoscopic disease. Patients were followed for a median time of 25 months (IQR 16–36). Colectomy free survival rates from vedolizumab initiation were 67% at one year and 55% at two years (Figure 1, Panel A). At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At one and two years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab, respectively (Figure 1, Panel B). Vedolizumab was dose escalated to infusions every four weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1–8.2). No serious adverse events were recorded in our patient cohort.

Conclusion
Transitioning to vedolizumab following induction of remission with calcineurin inhibitors is effective and safe. Such a treatment strategy should be considered in patients with severe steroid-refractory ulcerative colitis, especially in cases of previous anti-TNF failure.
P449 Systematic review with meta-analysis: risk of lymphoma associated with anti-tumour necrosis factor (TNF) agents in inflammatory bowel disease
Authors: CHUPIN A , Perduca V , Bellanger C , Carbonnel F , Dong C 
Published: January 2020

Abstract

Background
We performed a systematic review and meta-analysis to investigate the risk of lymphoma in patients with IBD treated with anti-TNF agents and thiopurines, alone or combined.

Methods
We conducted a systematic review of studies including IBD patients treated with anti-TNF and/or thiopurines from Pubmed, Embase and Cochrane databases until May 1, 2019. Two methodology reviewers (AC, CD) separately and repeatedly screened and selected studies according to study selection criteria, collected data and assessed quality. The meta-analysis used the mixed-effect Poisson models (particularly generalised linear mixed models, GLMM) to estimate incidence rate ratios (IRRs) in patients unexposed and exposed to anti-TNF, thiopurines and combotherapy (anti-TNF and thiopurines).

Results
We identified 4 998 citations. Fourteen studies were eligible for the meta-analysis. There were 8 observational studies involving 265 171 patients and 6 randomised controlled trials involving 2 311 patients (table). As compared with unexposed patients, those exposed to anti-TNF, thiopurines and combotherapy had IRRs (per 1000 patient-years) of 1.66 ([CI 95%, 1.18–2.35], p = 0.004 with I2 = 0%), 3.32 ([CI 95%, 1.87–5.90], p &lt; 0.001 with I2 = 66.83%) and 2.64 ([CI 95%, 1.17–5.93], p = 0.02 with I2 = 1.69%), respectively. The risks of lymphoma did not differ between anti-TNF and thiopurines, between combotherapy and anti-TNF and between combotherapy and thiopurines (table). The results were unchanged when the meta-analysis was restricted to observational studies.

Conclusion
These results show that the risk of lymphoma is higher in IBD patients treated with anti-TNF monotherapy and combination therapy compared with patients unexposed to anti-TNF or thiopurines.
P473 Long-term follow-up of switching from original adalimumab to adalimumab biosimilar: real-world data in IBD
Authors: Padilla Suarez C , Webb K , Persad N , Sercombe J , Tyler E , Klimova K 
Published: January 2020

Abstract

Background
Studies have reported good efficacy outcomes for patients with inflammatory bowel disease (IBD) treated with biosimilars. There are limited long-term data. We assessed the long-term efficacy data and safety after switching from adalimumab to adalimumab biosimilars in patients with IBD.

Methods
A prospective single-centre observational study involving patients with Crohn’s disease or ulcerative colitis switched from adalimumab to adalimumab biosimilar and reviewed up to 12months. Efficacy and loss of response were measured using the Harvey–Bradshaw (HB) index and partial Mayo score for patients with Crohn’s disease and ulcerative colitis respectively. Blood tests including C-reactive protein, adalimumab drug levels and anti-drug antibodies were monitored. We have recorded side effects and possible serious adverse effects. The plan is to continue the study for 24 months.

Results
109 patients with IBD have completed at least 6 months of treatment with adalimumab biosimilar, 12 of which have ulcerative colitis and 97 Crohn’s disease. Most of them (88%) continued on biosimilar after 6 months. Patients discontinued the therapy due to loss of response or development of antibodies in one case. Two patients were switched to a different biosimilar due to the presence of side effects which were however not serious. Of those who remained on the treatment, 74.5% were in clinical remission at 6 months and 71.4% at 9 months. HB index, partial Mayo score, C-reactive protein and adalimumab drug levels did not show significant changes. We have not reported any serious adverse events. We hope than by February, at least 60% of these patients will have been on Adalimumab for 12 months and further amended date would be added.

Conclusion
Most of the patients switching from original adalimumab were maintained on biosimilar at 6 and 12months of follow-up with similar efficacy and safety as the original drug.
P477 Italian real-life study evaluating the long-term effectiveness of vedolizumab for the treatment of inflammatory bowel disease: the elderly cohort
Authors: Pugliese D , Privitera G , Armuzzi A 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) is the first biological therapy for Inflammatory Bowel Disease (IBD) tested, in pivotal trials, on patients up to 80 years old and has usually been presented as a safer choice in frail patients. However, real-world data on the effectiveness and safety of VDZ in elderly (≥ 65 years) are scarce. The aim of this study is to explore the effectiveness and safety of VDZ in a large real-life cohort of elderly IBD patients, with a 2 years follow-up.

Methods
The Long-term Italian Vedolizumab Effectiveness (LIVE) study included CD and UC patients started on VDZ from April 2016 to June 2017 at 40 centres of the Italian Group for the study of inflammatory bowel disease (IG-IBD). Patients were prospectively followed-up to June 2019. Co-primary endpoints were to evaluate cumulative VDZ treatment persistence and safety.

Results
Of 966 patients, 174 (18%; 81 CD, 93 UC) were ≥ 65 years old at enrolment. Mean disease duration at baseline was 10.9 years ± SD10 (CD 12.5 ± 11, UC 9.6 ± 9). VDZ was used as a first biologic therapy in 78 patients (44.8%). 25 patients (14.4%) had a history of previous cancer. The majority of CD patients had a stricturing behaviour (45, 55.6%) and had already undergone surgery (41, 49.4%). 48 UC patients (51.6%) had extensive colitis. Moderate-to-severe endoscopic activity was present in 80% of CD and in 92% of UC, according to SES-CD and endoscopic Mayo score, respectively. Cumulative VDZ treatment persistence at 12 and 24 months was 71.8% (71.6% CD and 72.0% UC) and 54% (54.2% CD and 53.8%% UC), respectively. 52.9% (40 CD; 52 UC), 4.0%, 3.5%% and 2.9% of patients were on concomitant steroids at baseline, 6, 12, and 24 months, respectively. Clinical remission at 12 and 24 months was achieved in 28.7% (31 CD and 29 UC) and in 31.6% (25 CD and 30 UC) of patients. Mean C-reactive protein was 15.6 mg/l ± SD 20 (CD 15.9 ± 21; UC 15.2 ± 19) at baseline and dropped to 8.4 mg/l ± 10 (CD 8.0 ± 8, UC 8.9 ± 11) at 12 months and to 5.9 mg/l ± 6 (CD 5.8 ± 5, UC 6 ± 7) at 24 months. Dose escalation was necessary for 20.3% and 24.7% of patients within the first 12 and 24 months. 44 adverse events were reported: 16 infections.,6 new diagnosis of cancer/dysplasia (2 colon, 1 kidney, 1 prostate, 1 lung, 1 melanoma), 4 arthritis, 3 skin rash, 2 drug-induced cholestasis,11 miscellaneous. 11 patients (6.3%) underwent VDZ withdrawal because of adverse events (6 new diagnosis of cancer/dysplasia; 4 infections; 1 cholestasis). One patient died for pneumonia complications.

Conclusion
In this preliminary analysis of the largest reported real-world cohorts of elderly IBD patients treated with VDZ, up to 55% of patients persisted on therapy after two years; an acceptable safety profile was observed throughout the entire follow-up period.
P479 The effect of adalimumab on linear growth in children with Crohn’s disease: a post hoc analysis of the PAILOT randomised control trial
Authors: Matar M , Shamir R , Turner D , Broide E , Weiss B , Ledder O , Guz-Mark A , Rinawi F , Cohen S , Topf-Olivestone C , Shaoul R , Yerushalmi B , Ben-Horin S , Assa A 
Published: January 2020

Abstract

Background
Growth impairment is common in children with Crohn’s disease. We aimed to assess the effect of adalimumab treatment on linear growth in children with Crohn’s disease in a post-hoc analysis of the PAILOT randomised controlled trial.

Methods
Children 6–17 years old with moderate-to-severe Crohn’s disease, naïve to biologic treatment, who responded to adalimumab induction, were assessed at week 4, 8 andevery8 weeks thereafter until week 72 for anthropometric parameters (height, weight and body mass index, BMI, Z-scores). We also analysed the associations of these parameters with clinical disease activity, inflammatory biomarkers, faecal calprotectin and adalimumab trough concentration.

Results
Overall, 66 patients had available anthropometric parameters between week 4 to 72(29% females, mean age 14.3 ± 2.6 years). The median improvement of height z–score /month was +0.014, 95% CI 0.004–0.024, p = 0.006 with an overall improvement during the study period from -0.62 (IQR −1.6–0.15) to −0.33 (IQR -1.3–0.5). The median increase of weight z- score/month was +0.025, 95% CI 0.015–0.034, p = 0.025 [overall increase from -0.54 (IQR −1.2–0.15) to −0.1, (IQR -0.9–0.6)], whereas the median increase in BMI z –score/month was +0.02, 95% CI 0.008–0.031, p = 0.001 [overall increase from −0.4 (IQR −1.0–0.5) to 0.0 (IQR −0.8–0.9)]. There was a significant correlation between paediatric Crohn’s disease activity index and erythrocyte sedimentation rate at week 4 and height z-score changes (p = 0.043 and p = 0.048), respectively, and a marginal correlation with C-reactive protein (p = 0.06). There was a significant correlation between sustained clinical and biologic remission (weeks 4–72) and changes in height z-score during follow-up (p = 0.001). Faecal calprotectin, adalimumab trough concentrations and combination therapy with an immunomodulator were not associated with height z-score changes.

Conclusion
Adalimumab treatment significantly improved linear growth, and normalised weight and BMI in children with moderate-to-severe Crohn’s disease.
P481 Repeated surgery for recurrent ileocolonic Crohn’s disease: does the outcome keep worsening operation after operation? A comparative study of 1224 consecutive procedures
Authors: Colombo F , Frontali A , Baldi C , Lamperti G M B , Maconi G , Ardizzone S , Foschi D , Sampietro G 
Published: January 2020

Abstract

Background
Despite relevant improvement in the medical treatment of ileocolic Crohn’s disease (CD), still surgery is needed in 80% of patients and clinical recurrence occurs in more than 50% of cases after surgery. Aim of the study is to assess the outcome for patients undergoing repeated surgery for recurrent CD.

Methods
All patients undergoing surgery for ileal or colonic CD between 1993 and 2018 in our tertiary care centre were retrospectively reviewed. We considered all small bowel resections, colonic resections, conventional (SP) and not conventional strictureplasties (NCSP).

Results
In the study period, 1224 CD patients underwent a surgical operation. We performed 713 (58.2%) primary operations (1R), 325 (26.5%) re-operations (2R group) and 186 (15.3%) three or more interventions (≥3R group). A CD diagnosis and the time of first surgery at early age were a negative prognostic factor, favouring repeated surgery in the time (R1 vs. R2p &lt; 0.004 and R1 vs. ≥3R p &lt; 0.0001 comparing age at diagnosis; R1 vs. R2p &lt; 0.0001 and R1vs. ≥3R&lt; 0.0001 regarding the time to firstt surgery). The indication for surgery (stenosis, fistula/abscess and refractoriness to medical therapy) does no’t change significantly with the number of surgeries regarding the analysis of variance of the three groups (p = 0.3). In the repeated surgery (R2 and ≥3R group) the incidence of recurrence appears to be more frequent at the anastomotic site for the 2R group (197/325, 61% vs. 103/186, 55% p &lt; 0.05) and at SP site for the ≥3R group (19/325, 5% vs. 23/186, 12% p &lt; 0.01). The ≥3R group underwent to a higher number of strictureplasties in comparison to the 1R group (100/186, 53% vs. 305/713, 43% p &lt; 0.0001) and the 2R group (100/186, 53 vs. 127/325, 43% p &lt; 0.0004). The duration of the surgical procedure tends to be higher for the ≥3R group but without reaching a statistical significance (p = 0.2). Postoperative morbidity (Clavien Dindo I-V) was increased in the 2R and in the ≥3R group but not in a significant way: (1R group n = 187 (26%); 2R group n = 102 (31%); ≥3R group n = 64 (34%); 1R vs. 2R p = 0.1, 2R vs. ≥3R group p = 0.5). In particular there was no difference between the groups in the incidence of severe postoperative morbidity (Clavien-Dindo ≥3): 1R group n = 69 (9.6%); 2R group n = 37 (11%); ≥3R group n = 24 (12%); 1R vs. 2R p = 0.4, 2R vs. ≥3R group p = 0.7.

Conclusion
In this series, we treated more than 40% of the small bowel segments with SP and NCSP at first surgery. This percentage gradually increases to 49% in 2R group and to 53% in ≥3R group. Even if the overall morbidity rate was higher, repeated surgery for recurrent CD doesn’t appear to be related to an increased risk of severe postoperative morbidity in our experience.
P484 Effectiveness and safety of ustekinumab in patients with Crohn’s disease: a real-world experience
Authors: Mohammad D , Alshahrani A , Bao Y , Alramdan R , Rajani A , Chauhan U , Salena B , Tse F , Greenwald E , Albashir S , Halder S , Armstrong D , Marshall J , Narula N 
Published: January 2020

Abstract

Background
Ustekinumab is a monoclonal antibody against the p40 subunit of IL-12 and IL23 which has been proven efficacious and safe in clinical trials, yet, real-word effectiveness studies are lacking. We aimed to determine the effectiveness and safety of ustekinumab in Crohn’s disease patients in a usual care setting, as well as to identify factors that predict response to treatment.

Methods
This was a retrospective review of patients with Crohn’s disease who had received ustekinumab at McMaster University Medical Center between January 2017 and August 2019. The primary endpoints were 12-month rates of clinical response, clinical remission and endoscopic improvement (according to physician assessment). We also performed a multivariate logistic regression to determine independent predictors of treatment effectiveness. Key safety outcomes were rates of adverse events including infections.

Results
We included 123 patients with Crohn’s disease, 58.8% of which had ileocolonic disease. Of these patients, 79.5% had prior TNF-antagonist exposure and 17.1% had previously used vedolizumab. The 12-month rate of clinical response, clinical remission, and endoscopic improvement, were 88%, 35%, and 47% respectively. On univariable analyses, longer disease duration was associated with a lower likelihood of achieving endoscopic improvement (OR 0.91 per year of disease duration, 95% CI 0.84–0.99, p = 0.03). On multivariate logistic regression, concomitant steroid use (OR 0.34, 95% CI 0.12–0.99, p = 0.049) and previous vedolizumab exposure (OR 0.13, 95% 0.02–0.77) were significantly associated with less likelihood of achieving clinical response at 12 months. Adverse events occurred in 13% of patients and infections occurred in only 1% of patients.

Conclusion
Ustekinumab has been effective in our real-world experience at achieving clinical response, clinical remission and endoscopic improvement in patients with Crohn’s disease. We found that concomitant steroid use and prior vedolizumab exposure were associated with a lower likelihood of clinical response. Further prospective data are needed to understand whether these are truly predictors of lack of response, or represent confounding from patients with more refractory disease.
P488 How reliable is the online medical information on paediatric inflammatory bowel diseases?
Authors: Velasco Rodríguez-Belvís M , Palomino Pérez L M , Sánchez Fernández-Bravo C , Sanchiz Perea A , Jose Luis L F , Domínguez Ortega G , Cañedo Villarroya E , Pedrón Giner C C , Jorge M P , Rodríguez Manchón S , Muñoz González A , Muñoz Codoceo R A 
Published: January 2020

Abstract

Background
Patients with paediatric Inflammatory Bowel Diseases (p-IBD) and their families widely use the Internet as a resource and tend to read the first page of 10 results. However, online content may be of questionable quality, and valuable information may be hard to find. This study aimed to (i) determine the average quality of online information on p-IBD and (ii) analyze whether it depends on the source of information.

Methods
A google search was performed on the 28 October 2019 using the keywords: ‘Crohn’s disease’, ‘ulcerative colitis’, ‘Inflammatory Bowel Disease’, ‘colonoscopy’, ‘endoscopy’, all of them combined with the terms ‘paediatric’ and ‘children’. We recorded the first 10 results for each search and excluded scientific papers, advertisements, videos and sites requiring subscription. Websites were classified according to their origin as hospital, professional society, government agency, health press or patient organisations. The quality of the information was assessed with the DISCERN instrument, a validated 16-point questionnaire (total score 16–80) to evaluate the quality of written information. DISCERN scores were graded as excellent (68–80), good (55–67), fair (42–54), poor (29–41) or very poor (16–28). In order to minimise subjectivity, four evaluators assessed the quality, and the mean total score was calculated for every selected website. The proportion of websites with excellent or good grading in each category was compared using the Fisher test.

Results
We identified 100 websites and 65 met the inclusion criteria. The type of authorship and DISCERN scores are shown in Table 1. The overall median DISCERN score was 40.8 [interquartile range, IQR 10.5]. Only 5 websites had an excellent or good score. The proportion of websites with excellent or good grading was significantly higher in those from government agencies and professional societies (33.3% and 30% vs. 2% and 0%, p &lt; 0.05). None of the health press websites showed excellent or good grading. Surprisingly, no websites from patient organisations were identified.

Conclusion
The quality of online information on p-IBD is highly variable. Most of the easily found websites are from hospitals, but professional societies and government agencies provide a higher quality of information. Improvement of online information on p-IBD is still needed.