bluuebunny/crossref_metadata_2025_split huggingface dataset:
P369 Dual Biologic in Moderate to Severe Pediatric Inflammatory Bowel Disease: A Case Series
Authors: Wlazło M , Jarzębicka D , Meglicka M , Kierkuś J 
Published: January 2022

Abstract

Background
Inflammatory bowel diseases (IBD) patients equipped in biological therapy embody a group with significant disease burden who have never succeeded conventional medication such as corticosteroids and thiopurines. Biologic agents are frequently used in the disease course, however they only result in, 1-year remission rates of approximately, 40% in given IBD populations. We aim to assess the efficacy and safety of concomitant use of, 2 biologic therapies including: anti-TNF (infliksimab, adalimumab) vedolizumab and ustekinumab in a refractory pediatric IBD cohort.

Methods
Eight children (5 ulcerative colitis, 1 ulcerative colitis/IBD-unspecified, 2 Crohn’s disease) with a disease duration of, 3,2 (8mth-9 years), initiated dual therapy at an age of, 10,8 (3–17) years after failing ≥2 biologic therapies. Three (37,5%) were treated with ustekinumab/adalimumab, 3 (37,5%) with vedolizumab/adalimumab and, 2 (25%) with infliksimab/vedolizumab. Primary outcome was clinical response after minimum, 3 dose of a second biological drug. It was defined as a decrease in PCDAI of at least, 12.5 points between baseline and, 3th dose of a second biological drug for CD, and a decrease in PUCAI of at least, 20 points between baseline and this time for UC.

Results
A clinical improvement was obtained in seven children (87,5%;, 4 UC, 1 UC/IBD-unspecified, 2 CD) in PCDAI/PUCAI scale after minimum, 3 dose of a second biological drug. Clinical response in patients: mean baseline PCDAI score was, 58,5 ±, 9 and, 21 ±, 19 after induction therapy with second biological drug, while PUCAI score was, 62 ±, 17 vs., 29 ±, 15, respectively. We reported one adverse event during treatment in the form of an anal abscess (UC, vedolizumab/adalimumab).

Conclusion
In pediatric IBD, combining biological agents seems to be safe and beneficial in selected patients. The application of dual biological therapy seems to be an appealing therapeutic option and may bring a possibility to better tailor and customize the therapies for patients. In a few publications the comparative efficacy and safety endpoints of dual therapies have been provided. Nevertheless, the clarification and justification of potential advantages of combined biological therapies in further studies such as randomized control trials are needed.
P380 Early improvement of endoscopic outcomes with risankizumab is associated with reduced hospitalisation and surgery rates in patients with Crohn’s disease
Authors: Feagan B G , Colombel J F , Panaccione R , Schreiber S , Ferrante M , Kamikozuru K , Lee W J , Griffith J , Kligys K , Kalabic J , Chen N , Dubinsky M 
Published: January 2022

Abstract

Background
Control of endoscopic inflammation like endoscopic remission is an important treatment target in Crohn’s disease (CD), as suggested in the STRIDE II guidelines. This study evaluated the relationship of early improvement in endoscopic outcomes on hospitalisation and surgery rates at, 52 wks in patients with CD treated with risankizumab (RZB).

Methods
This post-hoc analysis uses data from three double-blind, randomised Phase, 3 induction (ADVANCE and MOTIVATE) and maintenance (FORTIFY) trials evaluating the efficacy and safety of RZB in patients with moderate to severe CD. Patients who responded to, 12-wk induction therapy with RZB IV (600 mg or, 1200mg) in ADVANCE or MOTIVATE and received up to, 52 wks of maintenance therapy with RZB SC (180 mg or, 360 mg) in FORTIFY were analysed. Incidence rates (events/100 person-years) of CD-related hospitalisation, CD-related surgery (surgical procedures due to adverse events or complications related to CD), all-cause hospitalisation, and all-cause surgery were evaluated from the beginning of maintenance to wk, 52 and compared between patients who achieved endoscopic outcomes at end of induction (wk, 12) and those who did not. Endoscopic response, endoscopic remission and ulcer-free endoscopy (absence of ulceration) were defined using the Simple Endoscopic Score for CD (SES-CD) (Figure, 1–3), as scored by a blinded central reviewer.

Results
A total of, 298 patients were included in the analyses. Patients who achieved endoscopic response (n=121) at wk, 12 had a significantly reduced incidence rate of CD-related hospitalisation, CD-related surgery, and all-cause hospitalisation by wk, 52 compared to those who did not achieve an endoscopic response (n=177) at wk, 12 (Figure, 1). Additionally, patients who achieved endoscopic remission at wk, 12 (n=83) had a significantly reduced incidence rate of CD-related hospitalisation, CD-related surgery, and all-cause hospitalisation by wk, 52, compared to those not achieving endoscopic remission at wk, 12 (n=215) (Figure, 2). Though not statistically significant, numerically lower rates of all-cause surgery were observed for patients who achieved endoscopic remission or endoscopic response at wk, 12. Significantly lower rates of CD-related hospitalisation, CD-related surgery, all-cause hospitalisation, and all-cause surgery by wk, 52 were observed among patients who achieved ulcer-free endoscopy (absence of ulceration) (n=70) vs those who did not (n=228) at wk, 12 (Figure 3).

Conclusion
Early improvement of endoscopic outcomes at wk, 12 is associated with significant reductions in hospitalisations and surgeries through, 52 wks for patients receiving RZB therapy.
P430 Longer-term tofacitinib effectiveness for the treatment of ulcerative colitis: Two-year outcomes from a UK observational cohort study
Authors: Honap S , Sharma E , Ray S , Mawdsley J , Anderson S , Samaan M , Pavlidis P , Irving P 
Published: January 2022

Abstract

Background
Tofacitinib is an oral small molecule inhibitor licensed for the treatment of ulcerative colitis (UC). Whilst real world data has been presented, outcomes beyond, 26 weeks are limited. The objective of this study was to assess the persistence and long-term effectiveness of tofacitinib.

Methods
We conducted a retrospective observational cohort study, using a prospectively maintained database, at a large UK IBD tertiary referral centre. The primary objective was to assess the proportion of patients in deep remission at one year. Deep remission was defined as corticosteroid free clinical remission (CSFR) and endoscopic remission (Mayo Endoscopic Subscore (MES) of, 0 or, 1). All adult patients receiving tofacitinib for moderate to severe UC were included from October, 2018 to October, 2021. Disease activity was assessed using the Simple Clinical Colitis Activity Index (SCCAI); clinical response and remission were defined as a reduction of SCCAI ≥3 and a SCCAI ≤2, respectively. All analyses were based on an intention-to-treat principle, and we used non-responder imputation in cases of missingness.

Results
In total, 103 patients were included with a median follow up duration of, 53 weeks (range, 1–156). Prior to treatment, patients had active disease clinically (median SCCAI, 7 (range, 0–15) and endoscopically (median MES, 3) with, 54% on corticosteroids. The cohort had refractory disease;, 90% were anti-TNF-experienced and, 48% had prior exposure to at least two different biologic classes. Table, 1 shows the baseline characteristics of the cohort and figure 1 shows patient disposition in the study. Median treatment duration on, 10mg bd was, 18 weeks (range, 1–135);, 27% (n=15) were on, 10mg BD at one year and, 11% (n=3) at two years. At, 52 weeks, 61% were in CSFR, 38% in endoscopic remission, and, 36% in deep remission (figure 2). Deep remission was not associated with baseline variables, including prior biologic exposure or disease severity on univariate analyses. Faecal calprotectin fell from median, 451ug/g [range, 5-6020] at baseline to, 86ug/g [range, 5-2360] at week, 52 (n=41, p&lt;0.001), but CRP change was not significant. Three-quarters of those remaining on tofacitinib at, 104 weeks (n=27) were in deep remission. The Kaplan Meier estimated probability of remaining on tofacitinib was, 62% (95% CI, 51–71%) at week, 52 and, 44% (CI, 95%, 32–54%) at week, 104 (figure 3).

Conclusion
Longer term effectiveness and treatment persistence data in a cohort of highly refractory UC patients is reassuring.
P559 Cannabis Improves Sleep Quality in Patients with Inflammatory Bowel Diseases in a Prospective Observational Study
Authors: Hirsch A , Seidenberg C , Fliss Isakov N , Meiri D , Maharshak N 
Published: January 2022

Abstract

Background
Poor sleep is associated with adverse health consequences and was shown to be associated with subclinically active inflammatory bowel diseases (IBD).
Altered sleep patterns in IBD patients were associated with frequent disease flares and lower quality of life.
The aim of this study was to assess the effect of cannabis use on sleep quality in IBD patients.

Methods
We conducted a prospective observational cohort study enrolling 160 IBD patients who were prescribed medical cannabis.
Patients who changed medication during the trial, reported use of cannabis 3 months before the trial, or failed to follow up were excluded from the analysis.
Patients filled questionnaires at baseline and after 3 and 6 months of therapy. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI).

Results
A total of 91 patients were included, of these 62.6(57%) were males and 74(81.3%) were diagnosed with Crohn’s disease (CD).
Their median age was 36.71 years (range 20.1–73.2) and their median disease duration was 9 years (range 0.5–55.1).
The median cannabis dose prescribed was 20 grams (range 10–40).
Patients reported an improved sleep quality with decreased mean PSQI score after 3 months (7.1±3.85 vs 7.8±3.9, p=0.004) and further improvement after 6 months (6.9±3.7 vs 7.8±3.9, p=0.006) of cannabis therapy, compared to baseline.
Cannabis therapy was safe with no severe adverse or side effects.

Conclusion
Cannabis use is an effective and safe intervention to improve sleep quality in IBD patients.
The impact of cannabis on the disease activity and its association with sleep improvement in these patients should be further explored.
P563 Association between smoking status and the efficacy and safety of tofacitinib in patients with Ulcerative Colitis: Data from the tofacitinib clinical programme
Authors: Rubin D T , Torres J , Regueiro M , Reinisch W , Prideaux L , Kotze P G , Tan F H , Gardiner S , Mundayat R , Cadatal M J , Ng S C 
Published: January 2022

Abstract

Background
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Efficacy and safety of tofacitinib were evaluated in randomised, placebo-controlled Phase (P)2 (NCT00787202) and P3 (NCT01465763; NCT01458951; NCT01458574) studies, an open-label, long-term extension (OLE) study (NCT01470612) and an ongoing P3b/4 study (NCT03281304). Ex-smokers have an increased risk of UC, but the response to therapy in these patients (pts) has not been previously evaluated. We assessed the impact of smoking status on the efficacy and safety of tofacitinib in the UC clinical programme.

Methods
Efficacy endpoints and adverse events (AEs) were evaluated by smoking status (ever smokers [current and ex-smokers] and never smokers) in P2 (safety only)/P3/OLE/P3b/4 studies. Efficacy endpoints were summarised by treatment allocation; pt characteristics and AEs were summarised by tofacitinib predominant dose.

Results
This analysis included 1156 pts (ever smokers, n=416 [36.0%; current smokers, n=59 (5.1%); ex-smokers, n=357 (30.9%)]; never smokers, n=740 [64.0%]; Table 1). Compared with never smokers, ever smokers were older and more likely to have a prior history of myocardial infarction, diabetes mellitus, or ischaemic or coronary heart disease. The proportion of pts achieving efficacy endpoints was generally similar across tofacitinib treatment groups regardless of smoking status (Table 2). AEs were reported in 88.7% of ever smokers and 83.8% of never smokers. Overall, 60.6% of ever smokers had an infection, specifically 10.8% had herpes zoster (non-serious and serious), 12.0% had a Clostridioides difficile infection and 19.5% had a lower respiratory tract infection; corresponding values for each AE among never smokers were 53.1%, 6.8%, 8.5% and 11.4% (Table 1). Major adverse cardiovascular events were reported in 1.0% of ever smokers and 0.7% of never smokers; thromboembolic events were reported in 1.0% of ever smokers and 0.9% of never smokers. Malignancies (excl. non-melanoma skin cancer [NMSC]) occurred in 2.5% of ever smokers and 1.5% of never smokers; NMSC occurred in 3.7% and 1.0%, respectively. In total, 0.6% of never smokers had colorectal cancer and there were no cases in ever smokers.

Conclusion
The efficacy and safety of tofacitinib were generally similar in ever smokers and never smokers. This study is limited by the combined analysis of current and ex-smokers and unknown factors such as the degree of smoking and the time between smoking cessation and UC diagnosis. These data are consistent with previous reports in the general population and pts with UC.1,2

References
1. Meserve J et al. Clin Gastroenterol Hepatol 2019; 7: 1533–1540.
2. Rogers MA et al. PLoS One 2012; 7: e42091.
P608 Systematic review: The impact and importance of body composition in Inflammatory Bowel Disease
Authors: Ding N , Tassone D , Al Bakir I , Wu K , Connell W , Thompson A , Malietzis G , Lung P , Singh S , Choi C H , Gabe S , Jenkins J , Hart A 
Published: January 2022

Abstract

Background
Alterations in body composition are common in Inflammatory Bowel Disease (IBD) and have been associated with differences in patient outcomes. We systematically reviewed the literature to consolidate knowledge on the impact and importance of body composition in IBD.

Methods
We conducted a systematic review according to PRISMA guidelines. A systematic search of MEDLINE, EMBASE and conference proceedings was undertaken by combining two key research themes: Inflammatory Bowel Disease and body composition. Studies which examined alterations in body composition in patients with IBD and studies which explored the impact of body composition on IBD therapeutic outcomes and prognosis were included.

Results
55 studies were included in this review. 31 studies focused on the impact of Inflammatory Bowel Disease on body composition with a total of 2,279 patients and mean age of 38.4 years. Of these, 1,071 (47%) were male. 1470 (64.5%) patients had CD and 809 (35.5%) had UC. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. 24 additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition were associated with poorer prognoses including higher rates of surgical intervention, post-operative complications, and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response were seen in patients with myopaenia.

Conclusion
Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impact of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.
P653 The changing epidemiology of IBD in the western world: a population-based study from Denmark
Authors: Agrawal M , Christensen H , Bøgsted M , Colombel J F , Jess T , Allin K 
Published: January 2022

Abstract

Background
Mitigating the burden of inflammatory bowel disease (IBD) in Western countries requires understanding how its epidemiology is evolving. We conducted a temporal analysis of the epidemiology of IBD between 1995 and 2018 in the Danish nationwide cohort.

Methods
We used the Danish Civil Registration System (CRS) to obtain demographic information on all residents in Denmark between January 1, 1995 and December 31, 2018. We obtained information on Crohn’s disease (CD) and ulcerative colitis (UC) diagnosis from the National Patient Registry (NPR) using International Classification of Disease 8/10 codes. IBD diagnosis was defined as having at least two CD- or UC-related registrations within a two-year period and the date of the first IBD-related registration was considered as the date of diagnosis. We estimated overall and annual incidence rates and prevalence of CD and UC standardized with respect to age and sex.

Results
52,407 individuals met the criteria for IBD diagnosis in the period 1995–2018, of which 17,355 (33%) were diagnosed with CD and 35,052 (67%) were diagnosed with UC. The median age at diagnosis (IQR) for CD and UC was 34 (22, 53) and 43 (29, 60) years, respectively. 9,745 (56.2%) and 18,332 (52.3%) individuals with CD and UC, respectively, were of female sex. During the study period, 1995–2018, the overall incidence rate (95% CI) rose from 9.2 (8.4, 10) per 100,000 person years (PY) to 18 (16.8, 19) per 100,000 PY for CD, corresponding to a 94.9% increase, and from 21.1 (19.9, 22.4) per 100,000 PY to 28.4 (27, 29.8) per 100,000 PY for UC, corresponding to a 34.1% increase. The incidence rates of CD and UC increased for all age groups, at different rates, highest for CD in age group 15–39 years (Figure). While CD incidence was consistently higher in women, increase in CD and UC incidence was comparable between both sexes. The prevalence of IBD also increased from 1995–2018 (225.6% and 218.4% for CD and UC, respectively) with the greatest increase in UC prevalence among individuals older than 40 years of age (248.4%).

Conclusion
The epidemiology of IBD has shifted in the last 20 years with a still increasing incidence of CD and UC in young adults, and a sharply increased prevalence in older age groups, especially for UC. These findings have implications towards understanding environmental shifts associated with this evolution as well as preparing for management of an aging IBD population.
P682 Predictors of response to biologics in Ulcerative Colitis: A population-based study from the epi-IIRN
Authors: Atia O , Lujan R , Greenfeld S , Kariv R , Matz E , Dotan I , Nevo D , Turner D 
Published: January 2022

Abstract

Background
Identifying prognostic factors of therapeutic failure, may facilitate balancing the risks and benefits of biologic treatment. In this population-based study, we aimed to explore predictors of therapeutic failure of biologics in Ulcerative Colitis (UC).

Methods
We retrieved data from two of four Health Maintenance Organizations in Israel, covering 38% of the population and part of the validated epi-IIRN IBD cohort. We included an inception cohort of UC patients, diagnosed since 2005, who were commenced on biologics. Those who underwent colectomy within 90 days from diagnosis were excluded. The primary outcome was therapeutic failure (i.e. discontinuation of treatment or need for colectomy or &gt;1 short steroid courses). The secondary outcome was primary non-response (PNR; i.e. therapeutic failure within 4 months of initiation). Predictors were sought through Cox proportional hazard model.

Results
A total of 910 patients were included (246 [27%] pediatric-onset, 664 [73%] adults) with a median follow-up of 7.9 years (IQR 4.9–12.0). The probability of PNR was 16% and of therapeutic failure 35%, 55% and 63% after one, three and five years after commencing biologics, respectively. Older age at diagnosis (HR 1.01 [95%CI 1.005–1.01]), number of flares prior to initiation of biologics (HR 1.1 [95%CI 1.05–1.2]) and steroid use prior to biologics (HR 1.3 [95%CI 1.1–1.6]) were associated with therapeutic failure. PNR was associated with use of steroids prior to initiation of biologics (HR 2.1 [95%CI 1.4–3.3]). Laboratory blood work, including CRP, ESR, albumin, leukocytes, hemoglobin and platelets did not predict therapeutic failure, whether at diagnosis (HR 1.1 [95%CI 0.6–2.0]) or at initiation of biologics (HR 1.2 [95%CI 0.7–2.1]).

Conclusion
One third of UC patients failed to response to biologic treatment within one year. Older age at diagnosis and disease severity prior to biologic treatment, reflected by number of flares and steroid use, predicted therapeutic failure.
P709 Distinct Pattern of Gut Microbial Dysbiosis in Crohn’s Disease and Intestinal Tuberculosis - A Machine Learning-based classification model
Authors: Markandey M , Bajaj A , Vuyyuru S K , Mohta S , Singh M , Verma M , Kumar S , Kante B , Kumar P , Makharia G , Kedia S , Ahuja V 
Published: January 2022

Abstract

Background
Crohn’s disease (CD) and intestinal tuberculosis (ITB) are chronic granulomatous inflammatory disorders characterized by a compromised mucosal immunity. Even with diverging etiologies, CD and ITB presents an uncanny resemblance in clinical manifestation resulting in diagnostic dilemma. The gut microbiota regulates myriad of gut mucosal immunological processes. Present study aims to decipher gut microbial dysbiosis in the two disorders and utilize the CD and ITB-specific gut dysbiosis to construct a machine learning (ML)-based predictive model, which can aid in their differential diagnosis.

Methods
Fecal samples from healthy controls (n=12) and from patients with CD (n=23) and ITB (n=25) were subjected to 16S (V3-V4) amplicon sequencing. Processing of raw reads, construction of ASV feature tables, diversity, core microbiome analysis and ML classifier construction was done using QIIME2-2021.4. Differential abundance analysis (DAA) between the groups was carried out using Deseq2, after adjusting for the subject-specific confounders.

Results

The α and β diversity indices in CD and ITB groups were significantly reduced than HC group (p = 0.011 and 0.012 resp.), with no significant differences between the two diseases (Fig.1A, 1B). On comparison with HC, CD and ITB groups showed reduction in members of Firmicutes and Bacteroidetes, with enhancement of Actinobacteria and Proteobacteria (Fig.1C and 1D). DAA (FDR q &lt;0.1, FC &gt;2.5) between CD and ITB groups revealed expansion of Succinivibrio dextrinisolvens, Odoribacter splanchnicus, Megasphaera massiliensis, Bacteroides uniformis and B.xylanisolvens in CD group, while Clostridium sp., Haemophilus parainfluenzae and Bifidobacterium sp. were elevated in ITB (Fig.2A). Random Forest-based ML model constructed on the basis of raw microbiome reads and using 80% of the samples to train the model, showed predictive accuracy of 0.78 (AUC=93%). (Fig.2B)

Conclusion
Our study shows that CD and ITB witnesses significant changes in gut microbial structure. With no significant differences in microbial diversity between two diseases, the signature of gut dysbiosis is distinct between CD and ITB. Exploitation of these differences to construct ML models can potentiate differential diagnosis of CD and ITB.