bluuebunny/crossref_metadata_2025_split huggingface dataset:
P338 Early proactive drug monitoring strategy of infliximab as monotherapy for inflammatory bowel disease in paediatric patients is associated with good sustained clinical remission
Authors: Girard C , Achkar S , Sassine S , Chapuy L , Jantchou P , Deslandres C 
Published: January 2022

Abstract

Background
Monotherapy with infliximab (IFX) could be as efficient as combotherapy with immunomodulators in the treatment and maintenance of remission for children with inflammatory bowel disease (IBD) if a proactive therapeutic drug monitoring strategy is adequately performed. This strategy may allow optimization of blood levels of IFX in order to obtain a sustained clinical response.

Methods
A retrospective study was conducted amongst children with IBD, aged from, 2 to, 18 years old and diagnosed between January, 2018 and June, 2020. All patients were treated with IFX less than, 30 days after diagnosis. Data concerning disease activity was collected at diagnosis, at one year after diagnosis. Close monitoring of IFX blood levels were collected before the third and fourth dose and regularly thereafter. Adjustments in IFX dose per infusion were made according to blood levels and clinical response. The primary outcome was clinical remission, defined by a PUCAI or shortPCDAI score &lt;, 10 without the need of corticosteroid, at one year after diagnosis. The secondary outcomes measured were the median (interquartile range (IQR)) dose of IFX (in mg/kg) after a year of treatment, the median (IQR) number of changes of IFX dose, the time intervals between IFX infusions over a year, and the median (IQR) number of blood levels of IFX done in a year.

Results
A total of, 91 patients were included (81% Crohn’s disease; mean age at diagnosis was, 13.2 years (IQR = 11.3 to, 15.15)). After one year of treatment, 76 patients (83.5%) reached clinical remission. IFX was discontinued in, 13 patients:, 6 due to antibody occurrence, 5 because of treatment failure, 1 due to psoriasis and, 1 due to autoimmune hepatitis. In total, 61.5% of patients needed two or more IFX dose/interval optimization over the course of a year. At one year after diagnosis, the median IFX dose per infusion was, 8.78 mg/kg (IQR = 7.5 mg/kg to, 9.9 mg/kg) with infusions given, 6 weeks apart or less in, 82% of the patients. Patients who were diagnosed before the age of, 10 had a median IFX dose of, 9.43 mg/kg. The median number of IFX blood level dosage was, 4 per patient over a year (IQR=, 3.5 to 6).

Conclusion
Early treatment for IBD with IFX as monotherapy and a proactive optimization strategy is associated with a good sustained steroid free clinical remission. Most patients needed an increase of IFX dose during the first year of treatment. We therefore recommend to proactively monitor blood levels of IFX before the third and fourth dose of IFX and thereafter, in order to lower the risk of treatment failure and anti-infliximab antibodies occurrence.
P342 Trans-continental analysis of over, 2000 Inflammatory Bowel Disease patients implicates geography, disease type, and exposure to immunosuppression as drivers of SARS-CoV-2 seroprevalence: data from the ICARUS-IBD Consortium
Authors: Wong S Y , Helmus D , Marlow L , Martinez Pazos V , Brann S , Wellens J , Kedia S , Mak J W Y , Bergemalm D , Argollo M , Zaltman C , Steinwurz F , Rubin D , Allez M , Halfvarson J , Abreu M T , Lindsay J , Dutta U , Silverberg M S , Ng S C , Ahuja V , Watanabe K , Vermeire S , Colombel J F , Satsangi J 
Published: January 2022

Abstract

Background
IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America.

Methods
Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status.

Results
The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p&lt;0.001). Rates in Europe and North America were similar (range, 3.57%-8.94%). Overall, SARS-CoV-2 seroprevalence appears to be equal to or less than local populations (Table, 2). Seroprevalence rates were associated with IBD type (7.8% CD, 12.4% UC, 15% IBD-U, p&lt;0.001), smoking status (p&lt;0.001), and history of COVID diagnosis (p&lt;0.001) or COVID hospitalization (p=0.001), and any IMM (p&lt;0.001). (Table, 3). Whilst there were no significant differences in seroprevalence between patients receiving infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on IFX monotherapy and combination therapy (both p=0.002) and VDZ (p=0.02), compared with no medications (Figure 1).

Conclusion
We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.
P348 Top down versus step-up strategies to prevent postoperative recurrence in Crohn’s disease
Authors: Buisson A , Blanco L , Manlay L , Reymond M , Rouquette O , Dubois A , Pereira B 
Published: January 2022

Abstract

Background
The best management after ileocolonic resection is still unknown in Crohn’s disease (CD).
We compared step-up and top-down approaches to prevent short and long-terms postoperative recurrences in CD patients.

Methods
From a comprehensive database, consecutive CD patients who underwent intestinal resection (2014–2021) were included. Top-down (biologics started within the first month after surgery) or step-up strategies (no biologic between surgery and colonoscopy at, 6 months) were performed with systematic colonoscopy at, 6 months and therapeutic escalation if Rutgeerts index was ≥i2a (endoscopic postoperative recurrence). Propensity score analysis (Inverse probability of treatment weighting) was applied for each comparison adjusted on the following parameters: gender, prior history of bowel resection, smoking habits, CD location, CD behaviour, resection length &gt;, 30 cm, age and the number of biologics before surgery.

Results
Among, 115 CD patients, top-down was the most effective strategy to prevent endoscopic postoperative recurrence (Rutgeerts index ≥ i2a) (46.8% vs, 65.9%, p=0.042) and to achieve complete endoscopic remission (Rutgeerts index = i0) (45.3% vs, 19.3%, p=0.004) at, 6 months. The median time of follow-up (ending at the time first progression of bowel damage or last follow-up) was, 41.9 months [21.4–76.2]. We did not observe any significant difference between the two groups regarding clinical postoperative recurrence (hazard ratio (HR) = 0.86 [0.44–1.66], p=0.66) and progression of bowel damage (HR = 0.81 [0.63–1.06], p=0.12). Endoscopic postoperative recurrence (Rutgeerts index ≥ i2a) at, 6 months was associated with increased risk of clinical postoperative recurrence (HR = 1.97 [1.07–3.64], p, 0.029) and progression of bowel damage (HR = 3.33 [1.23–9.02], p=0.018). Among the subgroup without endoscopic postoperative recurrence (Rutgeerts index = i0 or i1) at, 6 months, the risks of clinical postoperative recurrence and progression of bowel damage were significantly improved in the top-down group compared to step-up (HR = 0.59 [0.37–0.94], p = 0.025) and HR = 0.73 [0.63–0.83], p&lt;0.001, respectively). In contrast, when focusing on patients experiencing endoscopic postoperative recurrence (Rutgeerts index ≥ i2a) at, 6 months, top-down approach was associated with higher likelihood of clinical postoperative recurrence (HR = 1.92 [1.02–3.59], p = 0.042) and progression of bowel damage (HR = 1.58 [1.03–2.42], p = 0.035).

Conclusion
Top-down strategy should be preferred to step-up approach to prevent endoscopic postoperative recurrence as well as clinical postoperative recurrence and progression of bowel damage in most of the patients with Crohn’s disease after bowel resection.
P355 Exceeding treatment expectations in Crohn’s disease: transmural healing and a new definition of deep remission
Authors: Castiglione F , Imperatore N , Testa A , de Sire R , Nardone O M , Ricciolino S , Di Luna I , Patturelli M , Villani G D , Olmo O , Rispo A 
Published: January 2022

Abstract

Background
While mucosal (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn’s disease (CD), little is known about the real significance and clinical impact of deep remission (DR). The aim of this study was to better explore the concept of DR, towards a direct correlation between MH, TH and biomarkers.

Methods
A real-world observational longitudinal study was performed to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive patients with CD undergoing maintenance treatment with biologics. A ROC curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, CD patients achieving CR, MH and TH, in association with the target FC and CRP values, were considered in DR.

Results
Among, 118 CD patients, CR, MH and TH were achieved in, 74 (62.7%), 52 (44.1%) and, 38 patients (32.2%), respectively. After, 2 years, the mean FC levels decreased from, 494 ±, 515.4 μg/gr to, 260 ±, 354.9 μg/gr (p&lt;0.01). Using the ROC curve analysis, a FC cut-off value of, 94 μg/gr was associated with both MH (sensitivity, 94.2%, specificity, 84.8%, PPV, 83.05%, NPV, 94.92%, AUC, 0.95) and TH (sensitivity, 92.1%, specificity, 70%, PPV, 64.4%, NPV, 94.9%, AUC, 0.88). The MH/FC and TH/FC k of agreement was, 0.81 (p&lt;0.01) and, 0.58 (p&lt;0.01), respectively. CRP &lt;, 5 mg/L was associated with both MH (sensitivity, 96.1%, specificity, 62.1%, PPV, 66.7%, NPV, 95.35%, AUC, 0.85) and TH (sensitivity, 97.4%, specificity, 52.5%, PPV, 52%, NPV, 95.35%, AUC, 0.78). When considering CD patients with concomitant CR, MH and TH associated with a FC level &lt;, 94 μg/gr and CRP &lt;, 5 mg/L, DR was identified in, 33 patients (27.9%).

Conclusion
A FC cut-off of, 94 μg/gr and a normal CRP could be included in the definition of DR in association with CR, MH and TH. Thus, DR can be achieved in approximately, 30% of CD patients during maintenance treatment with biologics.
P358 Keeping it simple: How a streamlined referrals process reduces the time taken to initiate biologic therapy
Authors: Granger E , Heyes E , Cahoon E , Riley G , Kwok J , Shuttleworth E 
Published: January 2022

Abstract

Background
The process of commencing IBD patients on biologic therapy is logistically complex. Most biologic therapy is administered via a subcutaneous or intravenous route, so in addition to a negative pre-biologic screen, patients must be educated on subcutaneous self-administration or booked into an infusion’s clinic. A delay of over, 40 days in starting biologic therapy results in statistically worse self reported GI symptoms and endoscopic appearances at one year1. Therefore, reducing the time between the decision to initiate biologic treatment and the administration of the first dose is a key factor in improving outcomes.

Methods
A retrospective review of clinic letters, appointment dates and email exchanges was performed for all IBD patients commenced on outpatient biologic therapy (Adalimumab, Infliximab, Vedolizumab, Ustekinumab, Golimumab and Tofacitinib) by the Gastroenterology team at Lancashire Teaching Hospitals NHS Trust between February, 2019 and September 2021.
The length of time between the decision to initiate biologic therapy and the administration of the first dose was recorded in days. For cases where this time period was greater than, 28 days, the reason for the delay was categorised into either patient factors; logistical; outstanding biologic screen; outstanding clinical question; homecare delay or no single factor.
A tracking spreadsheet and generic referral email address were introduced in March, 2021 and the impact of these interventions was assessed via run chart.

Results
The median time period from the decision to initiate biologic therapy to administration of the first dose was, 35 days at the start of the study period, with, 67% of patients waiting over, 28 days.
Following the interventions in March, 2021, despite twice the number of patients, the median wait time was reduced to, 20 days with only, 23% of patients waiting over, 28 days.
Outstanding biologic screens and logistical factors such as delays in letter typing were the most common reasons for delays. Only, 17% of cases where communication was via email had a wait time of over, 28 days, compared to, 75% of cases where communication was via letter.

Conclusion
Simple adjustments such as a dedicated tracking spreadsheet and switching to email communication have a big impact on streamlining the process of initiating biologic therapy, almost halving the time taken from decision to initiate therapy to administration of the first dose.
1 System delays have real consequences: Impact of timing of biologic commencement on inflammatory bowel disease patient response A McCulloch, Journal of Crohn’s and Colitis, Volume, 13, Issue Supplement_1, March, 2019, Page S176
P360 The correlation between ophthalmological posterior segment findings and disease severity in patients with inflammatory bowel disease
Authors: Mitrovic M , Jeremić M , Zlatković D , Pantelić M , Vrinić-Kalem D 
Published: January 2022

Abstract

Background
Inflammatory bowel disease (IBD) is often associated with ophatlmological complications, such as blepharitis, conjunctivitis, episcleritis and iridociclitis. Although present in approximately quarter of all IBD patients, ophthalmological posterior segment findings are often overseen and possibly related to disease activity.

Methods
A total of, 136 patients, with previous IBD, underwent a complete ophthalmological examination, including fundus photography and optical coherence tomography/angiography (OCT/OCTA) using Optovue Avanti XR HD-OCT. The retinal foveolar avascular zone (FAZ) and choroidal thickness was measured using AngioPlex OCTA software. IBD activity was evaluated using adapted Mayo score and Crohn’s disease activity index (CDAI), for ulcerative colitis (UC) and Crohn’s disease (CD), respectively, as well as faecal calprotectin and serum C-reactive protein levels. UC remission based on the modified Mayo score was defined as stool frequency sub-score, 0 to, 1, rectal bleeding sub-score of, 0, and endoscopy sub-score, 0 to, 1. CD remission was defined with CDAI score bellow, 150. Patients with recent ophthalmological surgery, refractive errors greater than +3 or -3, as well as patients with retinopathies were excluded from analysis.

Results
We performed a cross-sectional study of, 272 eyes of, 136 IBD patients (91 UC and, 45 CD) average age, 45 years, of which, 87 females. A total of, 37 patients (27.2%), of which, 18 UC and, 19 CD patients, were defined as having an active disease. The most prevalent fundoscopic finding was vascular tortuosity, observed in, 47 eyes (17.2%). The difference between choroidal thickness between UC and CD patients was not observed (308±35µm vs, 314±29µm, p=0.32), as well as the FAZ difference (0.32 vs, 0.33 mm2, p=0.21). On the other hand, if we take in count only patients with active disease, the FAZ area of CD patients was significantly greater in comparison to UC patients (0.31 vs, 0.34 mm2, p=0.028). Correlation study showed significant correlation between choroidal thickness and CDAI (Rho, 0.448, p=0.036).

Conclusion
The choroidal thickness and FAZ area are ophthalmological parameters that could be easily obtained using OCTA and may be taken in count as possible non-invasive markers of disease severity, especially in CD patients.
P365 Weight gain after initiation of adalimumab in patients with Crohn’s disease
Authors: Darwin L , Wall C , Su H , Gearry R B 
Published: January 2022

Abstract

Background
Overweight and obesity are associated with increased risk of metabolic chronic diseases including cardiovascular disease and metabolic associated fatty liver disease. Weight gain post initiation of anti-tumour necrosis factor-alpha (TNFα) inhibitor medication is anecdotally common. This project aimed to determine whether weight gain occurs after inititiation of anti-TNFα inhibitor adalimumab.

Methods
A hospital database of, 277 patients that started on adalimumab between November, 2015 and November, 2020 to manage Crohn’s disease was retrospectively audited. Demographic and clinical data were extracted from the electronic medical record of patients. Weight and height prior to, and after, initiation of adalimumab were recorded and body mass index (BMI) was calculated. Anthropometric data was analysed using paired t-tests and statistical significance was assumed at p&lt;0.05.

Results
Patients initiated on adalimumab were mostly of New Zealand European ethnicity, 216/277 (78%), 159/277 (56%) were female, 129/277 (47%) had ileocolonic Crohn’s disease and, 199/277 (72%) had non-stricturing, non-penetrating disease. Weight before and after starting adalimumab was available for, 160/277 (58%) patients and increased by a mean of, 3.19 ±, 7.62% from, 74.74 ±, 18.98 kg to, 76.91 ±, 19.53 kg (2.18 kg (95% CI:, 1.31 to, 3.06, p &lt; 0.0001). Height (cm) was documented in, 97 (35%) patients. Mean BMI pre-adalimumab was, 25.89 kg/m2 (range, 16.05 to, 45.94 kg/m2) and increased by a mean of, 0.74 kg/m2 (95% CI:, 0.34 to, 1.13, p &lt; 0.001). Post-initiation of adalimumab patients with a BMI &lt;, 18.5 kg/m2 fell from five to three (3.1%) patients and the number of patients with a BMI ≥, 30.0 kg/m2 increased from, 18 to, 21 (21.6%) patients.

Conclusion
This single centre audit of patients starting adalimumab for management of Crohn’s disease found that significant weight gain is common. Less than two thirds of patients had weight documented at follow up appointments and height was documented in approximately a third of patients. Interventions to limit unintentional weight gain on initiation of adalimumab are warranted.
P379 Trends in Colectomy Rates and Biologic use over a, 30-year period: What has changed?
Authors: Doherty J , Stack R , Fennessy A , Cullen G , Mulcahy H , Sheridan J , Kevans D , Doherty G 
Published: January 2022

Abstract

Background
Novel medications including the introduction of biologic therapies in the last decade have expanded treatment options for patients with ulcerative colitis (UC). Large studies in the USA and Europe have shown colectomy rates in UC patients are reducing over the past two decades.

Methods
We performed a single-centre retrospective study of our prospectively maintained IBD database. Our aim was to look at changes in colectomy rates in patients with UC over the past three decades and need for biologic therapy. Basic demographics, need for biologic therapy and colectomy rates were collected. Need for colectomy and biologic therapy within, 10 years of diagnosis was determined across three groups dependent on decade of diagnosis.

Results
2229 patients with confirmed UC were included in our study. Median age at diagnosis was, 37 years [range, 4.9 -92.6]., 1210 [54.28%] were male., 595 patients were diagnosed between, 1990–2000, 795 between, 2000–2010 and, 790 between, 2010–2020. A total of, 366 (16.4%) patients had a colectomy during follow-up and, 363 (16.3%) were treated with biologic therapies. We found rates of colectomy within, 10 years of diagnosis have significant dropped over the past three decades. From, 1990 -2000, 595 patients were diagnosed with UC and, 131 [22%] patients had colectomies, in, 2000-2010, 794 patients were diagnosed with UC and, 135 [17%] had a colectomy and between, 2010-2020, 784 patients were diagnosed with UC and, 55 [7%] had a colectomy [p = &lt;, 0.001]. We found a significant increase in use of biologic therapy within the first, 10-years of diagnosis over the last three decades increasing from, 0.2% to, 5.3% to, 22.7% over the past decade [p = &lt;, 0.001].

Conclusion
Management of UC has changed over the past three decades including the introduction of multiple biologic therapies and the use of therapeutic drug monitoring has allowed a more personalised approach to management of UC. We can see from this study changes in the management of UC over the past decade have resulted in significant reduction in need for colectomy and an increase in the use of biologics.
P388 Asking teenagers and young adults with IBD; “what matters to you?”. A qualitative survey during the COVID-19 pandemic
Authors: King A , Speight A 
Published: January 2022

Abstract

Background
Good paediatric to adult transition of IBD care is important to prevent disengagement and poor disease outcomes [1]. The aim of this study was to qualitatively measure what is important to patients before they attended a new transitional service. There may be a dichotomy between the treating healthcare workers’ priorities and teenagers’ priorities that form a barrier to effective communication. Unprepared services can result in negative consequences for those involved [2] and a greater understanding of what matters to teenagers and young adults may improve the clinicians’ ability to facilitate the transition process.

Methods
We asked, 75 teenagers and young adults, aged between, 14 and, 21, who attended a new transitional service at a tertiary IBD unit in the North of England, to complete a survey prior to their clinic review. This ‘what matters to you’ survey included, 12 suggestions they could circle, with no limitations on how many many they selected, but a suggestion to choose up to, 3 topics. The survey was conducted during the COVID-19 pandemic and UK national lockdown, between September, 2020 and September, 2021.

Results

Conclusion
Inflammatory bowel disease is a condition with potentially a high morbidity from physical symptoms, and it is important not to forget this as a focus of a consultation. Medical therapies and their effects on the patient were important to, 48% of responders, and the transition process should include further education on treatment options with discussions of compliance. The impact on education and schooling feature as a significant topic and should be discussed during transition. Minimising the impact on education and employment should be considered when developing transitional services. Mental health wellbeing and body image were highly significant to a smaller number of patients and remain an important consideration. Interestingly not a single responder including the COVID-19 outbreak as a concern despite universally being on biological therapy or immunomodulators. It is important to note that whilst no patients reported ‘smoking, drugs and alcohol’ as important, risk-taking behaviours are increased in this patient population [3], they need to be sensitively discussed to become apparent and may be under-represented with the methodology used.
References
1. Brooks AJ, Smith PJ, Cohen R, et al UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care Gut, 2017;66:988–1000
2. van Rheenen, P, et al ECCO topical review on transitional care in inflammatory bowel disease. Journal of Crohn’s and Colitis, 2017;11,30-31
3. Brooks A et al. Health-related behaviours in young people with inflammatory bowel disease Gut, 2017;66:A153