bluuebunny/crossref_metadata_2025_split huggingface dataset:
P394 A prospective analysis of body composition in patients with Inflammatory Bowel Disease and changes during biologic therapy
Authors: Nguyen A , Burns M , Herath M , Holt D , Gibson P R , Milat F , Ebeling P , Moore G 
Published: January 2022

Abstract

Background
Low muscle mass is common in Inflammatory Bowel Disease (IBD) and is associated with poor quality of life and increased need for surgery. Our aim was to compare body composition in patients with IBD to controls, active and inactive IBD, and before and after biologic induction therapy.

Methods
Body composition was prospectively analysed in patients with IBD and gender-matched controls. Active disease was defined as a faecal calprotectin (FCP) ≥150 µg/g. In patients with active IBD commencing biologic therapy, body composition was measured at baseline and after induction, at ≥14 weeks. Patients were considered responders if the FCP reduced by ≥50%. All participants underwent whole-body dual-energy X-ray absorptiometry (DXA) (GE Lunar Prodigy), hand-grip strength, an International Physical Activity Questionnaire, Australian Eating Survey and a Subjective Global Assessment for malnutrition. Low skeletal muscle index (SMI) was defined as men ≤7.26 kg/m2 and women ≤5.45 kg/m2. Protein intake &lt;15% of total daily macronutrient intake was considered low.

Results
Patients with IBD (54% Crohn’s disease, 56% male) had a median age of, 29 years (IQR, 23–40) and, 5-year duration of disease (IQR, 1–11). Body composition was similar between, 48 patients with IBD and, 30 controls, including body mass index (25 vs, 23 kg/m2), fat mass (24.5 vs, 18.7 kg), estimated visceral adipose tissue (437 vs, 318 g), total lean body mass (46.6 vs, 47.9 kg) and appendicular skeletal mass (21.3 vs, 23.2 kg).

These markers were also similar when comparing active (n=28) to inactive (n=16) patients with IBD, stratified by gender. Low SMI was more common in the IBD cohort compared to controls (19% vs., 3%, p=0.048). Only one patient with low SMI had low hand-grip strength to meet the criteria for sarcopenia in the IBD cohort. More patients with IBD had low protein intake (13% vs, 0%, p=0.027) and were mild to moderately undernourished (25% vs, 0%, p=0.003) compared to controls. No difference was found with physical activity and hand-grip strength. In the IBD cohort, patients with low SMI were more likely to be undernourished (56% vs, 18%, p=0.019) but had similar protein intake compared to those with normal SMI. In, 7 of, 14 patients who responded to biologic therapy, SMI (7.9 to, 9 kg/m2, p=0.028) and total lean body mass (50.6 to, 54.3 kg, p=0.043) increased, while total fat mass or body mass index did not change. Low SMI was found in, 3 responders at baseline and increased after induction. There was no change in any body composition parameters in non-responders (n=7).

Conclusion
Body composition was similar between patients with IBD and controls, however low SMI was more common in IBD. Increasing muscle mass can be detected at ≥14 weeks after active disease is treated.
P395 Proactive Therapeutic Drug Monitoring May Reduce the Need for Combination Therapy in Inflammatory Bowel Disease Patients Treated with Infliximab
Authors: Doherty J , Varley R , Dunne C , Mc Carthy F , Hartery K , Mc Kiernan S , Kevans D 
Published: January 2022

Abstract

Background
Combination therapy with an immunomodulator [IM] is recommended by ECCO guidelines for patients with moderate-to-severe inflammatory bowel disease (IBD) treated with infliximab [IFX]. Combination therapy reduce anti-drug antibody (ATI) formation. Maintenance of adequate trough IFX levels is also known to reduce ATI formation.

Methods
We hypothesised that the use of proactive TDM in patients receiving IFX monotherapy would result in equivalent therapy outcomes compared with patients receiving IFX in combination with an immunomodulator. A pilot study using proactive TDM was undertaken at our unit with IFX and ATI levels, assessed at trough, in all IBD patients receiving IFX. We retrospectively evaluated the outcome of proactive IFX TDM on IFX therapy outcome. Baseline demographics, IFX dosing schedules and use of concomitant immunomodulators were documented. The study primary endpoint was time to infliximab discontinuation in IFX monotherapy and combination therapy groups.

Results
109 IBD patients receiving IFX with proactive TDM assessment were included. Median age, 36 years, 46% were female and, 36% UC., 37% and, 67% of patients were receiving IFX combination and monotherapy respectively. There was no significant difference in mean time to drug discontinuation between IFX combination and monotherapy groups, 2.33 [95% CI, 2.2–2.5] versus, 2.32 [95% CI, 2.0 –, 2.6] years respectively, p = 0.63. ATI concentrations [median] did not differ significantly between IFX combination and monotherapy groups, 2.9 AU/mL versus, 11.6 AU/mL, p = 0.54. In a multivariate analysis disease activity [p=0.005], low IFX levels [p=0.01] and elevated ATIs [p=0.001] were all independently associated with IFX discontinuation. There was no association between the use of IFX combination therapy and rates of IFX discontinuation, p=0.42.

Conclusion
Infliximab persistence, which is a proxy for successful therapy outcome, was similar in IFX monotherapy and combination therapy groups when proactive TDM was utilised. In the absence of concomitant immunomodulatory therapy, proactive TDM may improve IFX monotherapy outcomes, by maintaining higher IFX concentrations.
P402 Incidence and outcomes of herpes zoster in the ozanimod phase, 3 ulcerative colitis and relapsing multiple sclerosis clinical program
Authors: Siegmund B , Melmed G Y , Irving P M , Pai A , Patel A , Sheffield J K , Caldera F , Cree B A C , Dubinsky M C 
Published: January 2022

Abstract

Background
Patients with ulcerative colitis (UC) and patients with multiple sclerosis (MS) have an elevated risk of developing herpes zoster (HZ), caused by reactivation of latent varicella zoster virus (VZV). Increased incidence of HZ has been reported with sphingosine, 1-phosphatase (S1P) receptor modulators. This analysis examined the number of patients who failed screening due to a lack of demonstrated VZV immunity and the incidence of HZ from completed phase, 3 ozanimod clinical trials.

Methods
Safety results were included from True North (52-week trial) in patients with UC, and SUNBEAM (12-month trial), and RADIANCE (24-month trial) in patients with MS. All patients were required to have had a positive VZV IgG antibody status or completed VZV vaccination ≥30 days prior to randomization based on known effects of S1P modulators. Patients with a negative VZV antibody titer could choose to receive the VZV vaccination to qualify for the trial. Number of pre-screen failures because of lack of demonstrated immunity, occurrence of HZ, and association between HZ cases and lymphopenia were analyzed.

Results
Of, 1831 patients with UC screened for VZV immunity, 104 (5.7%) failed screening due to lack of documentation of VZV antibody or VZV vaccination ≥30 days before randomization;, 22% (23/104) subsequently received varicella vaccination and were rescreened and enrolled. Of, 3332 MS patients tested for VZV immunity, 309 (9.3%) tested negative and, 32% (98/309) of these patients were vaccinated prior to randomization. In the UC and MS trials, the incidence of HZ cases was low in ozanimod-treated patients (8 cases [1.0%] and, 5 cases [0.6%], respectively; Table, 1). All cases were distributed across a single dermatome, did not result in a complication of HZ, and were treated with oral antivirals while patients remained on ozanimod. None of the patients discontinued ozanimod because of HZ and none of the HZ cases were associated with grade, 4 lymphopenia (defined as an absolute lymphocyte count &lt;0.2 x, 109/L).

Conclusion
In the ozanimod phase, 3 UC and MS trials, 5%–10% of patients screened did not have demonstrated VZV immunity;, 22%–32% of these patients received varicella vaccination, were rescreened and enrolled. The overall HZ incidence in clinical trials was low (≤1% of patients), all cases were distributed across a single dermatome, and no serious or complicated cases occurred in ozanimod-treated patients with VZV immunity. Additional studies are warranted to evaluate the incidence of HZ in clinical practice.
P403 The role of Organic Cation Transporter (OCTN)-1 in predicting individual response to therapy in Ulcerative Colitis: towards a personalized approach
Authors: Puca P , Capobianco I , Petito V , Masi L , Fidaleo M , Del Chierico F , Palucci I , Lopetuso L R , Laterza L , Settanni C R , Parisio L , Bibbò S , Pugliese D , Armuzzi A , Pani G , Gasbarrini A , Scaldaferri F 
Published: January 2022

Abstract

Background
Ulcerative colitis is a chronic invalidating disease, whose therapeutic strategies include amino-salicylates, steroids, probiotics, immune-modulators, biologics, fecal microbiota transplantation and surgery. In clinical practice, there is little evidence available about elements that could predict response to each of the above-mentioned therapies. Our study suggests that OCTN1, an organic cation transporter directly involved in innate immunity, with its variants (C503L homozygous, heterozygous or T503F), could have a role in predicting individual response to biologic therapies (antiTNFa and vedolizumab).

Methods
In this prospective study, we enrolled a cohort of, 80 patients with active ulcerative colitis (51 in treatment with anti-TNF alpha agents and, 29 with vedolizumab), determining their OCTN1 genotype and evaluating their clinical response to therapy, calculated with clinical Mayo score, after six weeks (T1), six months (T2) and after three years (T3).

Results
Left colitis at diagnosis was more frequent in C503L patients (60% left colitis vs, 40% pancolitis) than patients with T503F (42.8% left colitis vs, 57.2 pancolitis). In the same way, the average age at diagnosis was sensibly lower in patients with T503F genotype (34.7 years C503L vs, 25 years T503F). We used clinical response at T2 (6 months) as a primary outcome of our study. Among patients under anti-TNF alpha therapies, patients with C503L genotype were divided into, 8 no responders and, 6 responders (43% responders vs, 57% no responders); patients with T503F genotype were divided into, 10 responders and, 2 no responder (80% responders vs, 20% no responders). On the contrary, patients under vedolizumab therapy showed different trends: patients with C503L genotype were divided into, 12 responders and, 3 no responders (83% responders vs, 17% no responders); patients with T503F genotype were, 1 responder and, 1 no responder (50% responders vs, 50% no responders). After, 3 years, patients responders to anti-TNF alpha therapies at T2, with T503F genotype, still maintain the response to the same drug.

Conclusion
Patients with the T503F genotype present an overall worse course of the disease, with a higher rate of pancolitis and younger age at diagnosis. Patients with the C503L genotype showed a better response to vedolizumab, whilst patients with the T503F genotype showed a better response to anti-TNF alpha. We can therefore conclude that the presence of the mutation (allele T) increases the response rate to anti-TNF alpha, especially for the homozygous mutated genotype (OR=371.82, p=0.009), but for the heterozygous genotype as well (OR=10.95, p=0.088).
P415 Improving food-related quality of life in Inflammatory Bowel Disease with a novel web-based intervention: a randomised controlled feasibility trial
Authors: Cox S , Wall C , Clarke H , Drysdale C , Czuber-Dochan W , Lomer M , Lindsay J , Whelan K 
Published: January 2022

Abstract

Background
Food-related quality of life (FR-QoL) refers to the psychosocial aspects and pleasure derived from food, eating and drinking. Impaired FR-QoL is prevalent in inflammatory bowel disease (IBD) and is associated with reduced intakes of fibre and certain micronutrients. Patient and health professional focus groups identified the need for web-based support and education on food in IBD, which was subsequently developed through experience-based co-design. The aim of this study was to establish the feasibility of a randomised controlled trial (RCT) investigating the effectiveness of the web-based intervention compared to usual care on FR-QoL in people with newly diagnosed IBD.

Methods
A randomised controlled feasibility trial was conducted in adults with Crohn’s disease or ulcerative colitis diagnosed in the preceding, 12 months. Patients with active and inactive IBD experiencing impaired FR-QoL (≤90 scored on the validated FR-QoL-29 questionnaire) were recruited. Participants were delivered usual care by their IBD team and were also randomised to either access to the web-based intervention (containing information and patient and clinician videos on various IBD-specific food and nutrition considerations) or no access to the website for, 12 weeks. Questionnaires were completed at baseline and end of trial to assess FR-QoL (FR-QoL-29), health-related quality of life (UK IBDQ), IBD distress (IBD Distress Scale) and anxiety and depression (HADS). Google Analytics was used to investigate usage of the web-based intervention.

Results
In total, 50 participants (ITT population) were recruited (81 screened), 30 randomised to the web-based intervention and, 20 to usual care, with, 48 completing the trial (PP population). In the ITT analysis, a greater increase in FR-QoL was observed in the web-based intervention (+11.7 SD, 18.2) than usual care group (+1.4 SD, 20.4, P=0.057), whilst IBD distress reduced in the web-based intervention (-6.8 SD, 26.6) and increased in the usual care group (+8.3 SD, 25.5, P=0.052). Participants in the web-based intervention group logged into the website an average of, 4.2 (SD, 2.9) times, and spent an average of, 13 minutes, 41 seconds (SD, 15 minutes, 1 second) on the website per visit. The most frequently accessed content covered dietary management of specific gut symptoms (accessed by, 52% of participants). In qualitative interviews the participants reported the intervention to be clear, user friendly, easy to navigate, and a good source of educational information.

Conclusion
This feasibility study demonstrates that a RCT of a web-based intervention is feasible and potentially effective in improving FR-QoL in IBD. An adequately powered RCT investigating the effectiveness of this intervention in IBD is feasible and now warranted.
P428 A Phase IB/IIA study of remestemcel-L, an allogeneic bone marrow derived mesenchymal stem cell product, for the treatment of medically refractory Crohn’s colitis: A preliminary analysis
Authors: Lightner A , Ream J , Nachand D , Fulmer C , Regueiro M , Steele S 
Published: January 2022

Abstract

Background
Mesenchymal stem cells (MSCs) have been successfully used for the treatment of perianal Crohn’s fistulizing disease by direction injection. However, no studies have looked at the direct injection of MSCs for luminal Crohn’s disease.

Methods
Following screening and informed consent, patients with medically refractory Crohn’s colitis who had a washout of at least, 4 weeks from monoclonal antibody treatment were randomized in a, 2:1 fashion to receive remestemcel-L, an ex vivo expanded allogeneic bone marrow derived MSC product versus placebo. If randomized to treatment, patients received, 150 million MSCs delivered via direct injection using a, 23 G sclerotherapy needle at the time of colonoscopy. Patients were included if they had medically refractory Crohn’s colitis defined as an established diagnosis for at least, 6 months prior to study enrollment and had lost response to at least one monoclonal antibody in the past, no small bowel involvement, and no colorectal stricture. Patients were evaluated with validated clinical and endoscopic scoring systems at, 2 weeks, 6 weeks, and, 3 months. Patients randomized to control crossed over at, 3 months to receive MSC treatment.

Results
A total of six patient have been enrolled;, 4 treatment and, 2 controls. There were, 7 reported adverse events, none of which were related to the investigational product (2 with eye pain, 1 with hiatal hernia, 1 with abdominal pain, 1 with partial small bowel obstruction, 1 with arthritis symptoms, 1 with Crohn’s flare requiring hospital admission and treatment with infliximab and intravenous corticosteroids). With regard to efficacy, in the treatment group (n=4), the SES-CD dropped from, 17 at baseline to, 5 by, 3 months, the CDAI from, 228 to, 200, and the fecal calprotectin from, 231 to, 67. In the control cohort, the SES-CD increased from, 15.5 to, 25, the CDAI increased from, 146 to, 158, and the fecal calprotectin increased from, 330 to, 505.

Conclusion
MSCs offer a safe alternative therapeutic for the treatment of medically refractory Crohn’s colitis. Early data suggests improved clinical and endoscopic scores by as early as two weeks following MSC delivery.
P432 Relationship between haemoglobin status and utility in patients with iron deficiency anaemia in inflammatory bowel disease: A post-hoc analysis of a phase, 3 clinical trial
Authors: Murphy D , Wooton P , Jacob I 
Published: January 2022

Abstract

Background
Iron deficiency anaemia (IDA) can significantly impair the health-related quality of life of patients with inflammatory bowel disease (IBD), but there is little evidence demonstrating a relationship between haemoglobin (Hb) and utility values. This study aimed to estimate preference-based health state utility values from Short-Form Health Survey (SF-36) data, stratifying by treatment received, and to investigate the relationship between Hb status and health-related quality of life.

Methods
A randomised phase, 3b clinical trial compared oral ferric maltol (FM) vs intravenous (IV) iron (ferric carboxymaltose (FCM)) in patients with IBD and IDA who were eligible for IV iron. This post-hoc analysis used patient-level data on SF-36 responses to generate Short-Form Six-Dimension (SF-6D) and EuroQol-5 Dimension (EQ-5D) health-state utility values using published algorithms. Utility values were further stratified by the proportion of patients achieving normalisation of Hb levels (Hb &gt;, 13g/dL for men and &gt;, 12g/dL for women).

Results
In the overall study population, mean (SD) SF-6D values were, 0.67 (±0.12) at baseline and, 0.70 (±0.13) at, 52 weeks. Mapped mean EQ-5D values were, 0.77 (±0.17) at baseline and, 0.78 (±0.19) at, 52 weeks. There were no significant differences in the mean utility estimates for patients receiving FM and FCM at any assessment point (Table, 1). Of note, 45.38% of patients randomised to the FCM arm received repeat treatments after the initial course administered at baseline. In the overall study population, mean utility estimates for patients in a normalised state were significantly greater than those estimated for patients in a non-normalised state (pooled analysis of all time points): SF-6D, 0.724 (95% CI:, 0.717–0.731) vs, 0.690 (95% CI:, 0.683–0.697), respectively, Pr (|T|&gt;|t|):, 0.001; EQ-5D, 0.834 (95% CI:, 0.826–0.842) vs, 0.792 (95% CI:, 0.782–0.802), Pr (|T|&gt;|t|):, 0.001. No statistically significant differences were observed between treatments in the normalised or non-normalised groups.

Conclusion
Oral ferric maltol results in similar utility scores to IV iron therapy with ferric carboxymaltose in patients with IBD eligible for intravenous iron therapy. Normalised Hb was associated with significantly better utility than non-normalised, demonstrating the value to patients of treating IDA in IBD. A cost-effectiveness analysis should be conducted to examine the incremental benefit of IV iron considering the large cost of treatment.
P450 Ustekinumab and vedolizumab for extraintestinal manifestations in inflammatory bowel disease
Authors: Livne-Margolin M , Ling D , Attia Konyo S , Haj O , Abitbol C M , Ben-Horin S , Kopylov U 
Published: January 2022

Abstract

Background
Extraintestinal manifestations (EIM) occur in up to 50 % of patients with inflammatory bowel disease (IBD) and are associated with significant morbidity and diminished quality of life. Ustekinumab (UST) and vedolizumab (VDZ) are effective for Crohn’s disease (CD) and ulcerative colitis (UC). However, their efficacy for treatment of EIM is not well established. The aim of our study was to compare the effectiveness of UST and VDZ for treatment of EIM in IBD.

Methods
We included IBD patients treated with VDZ or UST that are followed in the gastroenterology department of Sheba medical center between 2015 and 2021. Only patients with active EIM at the start of the treatment were included. The duration of follow- up was up to 52 weeks

Results
112 patients were included. Fifty-three patients (47%) were treated with ustekinumab and 59 (53%) with vedolizumab: 62(55%) women, 88% (n-99) had CD (52% had a small bowel,29% had both small bowel and colon disease location). Twenty-four patients (21%) were naïve to anti-tumor necrosis factor (TNF) inhibitors. The most common EIM was arthralgia (95/112, 84%). Patients treated with UST were more likely to be anti TNF experienced (n=51/53 [96%] compared with n=34/59 [58%], p&lt;0.0001). Only 1 UC patient (1/53, 2%) treated with UST was included compared with 12 UC patients (12/59, 20%) in the VDZ group.
Clinical response of EIM at week 52 was achieved in 42% of patients treated with UST (n-20/47) and 25% of patients (n- 13/52) treated with vedolizumab, this difference was not statistically significant (p =0.08). There was no difference between UST and VDZ regarding their effect on EIM at earlier timepoints (week 6, 14, 26) (n-9/39 [23%] vs. n-17/56 [30%] p=0.8, n-9/36 [25%] vs. n-17/55 [31%], p=0.6, n-14/41 [34%] vs. n-17/55 [30%], p=0.8, respectively). The difference between groups was also not observed for specific types of EIMs

Conclusion
In our retrospective study, no difference was found between VDZ and UST regarding their effect on EIM in IBD patients for up to 52 weeks of follow-up.