bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 >, 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<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

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<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<0.01) and, 0.58 (p<0.01), respectively. CRP <, 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 <, 94 μg/gr and CRP <, 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

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

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

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<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 < 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 < 0.001). Post-initiation of adalimumab patients with a BMI <, 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

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 = <, 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 = <, 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

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
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

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 <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

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

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 <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

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

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

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

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 >, 13g/dL for men and >, 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|>|t|):, 0.001; EQ-5D, 0.834 (95% CI:, 0.826–0.842) vs, 0.792 (95% CI:, 0.782–0.802), Pr (|T|>|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

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<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.
P460 A Real-World Picture of Adverse Drug Reactions in Inflammatory Bowel Disease
Authors: Lemos Garcia J , Rosa I , Saraiva S , Moleiro J , Claro I
Published: January 2022

Background

Patients with Inflammatory Bowel Disease (IBD) face complications of medical treatment that may compromise their health and the drugs’ therapeutic success. Real world data regarding adverse drug reactions (ADR) is crucial.

Methods

Unicentric retrospective study. All patients followed for IBD in a tertiary Portuguese hospital between 2015–2021 were included.

Results

328 patients included-55.8% women; age at last follow-up 53.4±16.7 years old; Crohn’s Disease (CD) in 53.0%; follow-up of 15.8±10.8years. Extraintestinal manifestations(EIM) occurred in 13.1%(n=43) patients, mostly arthropathy/arthritis(n=33). Current or previous treatment included salicylates in 69.5%, thiopurines 63.1%, corticosteroids 54.3%, methotrexate 5.5%, infliximab 38.4%, adalimumab 11.6%, ustekinumab 4.9% and vedolizumab 4.6%. In total, 124 ADR occurred in 97 patients(28.7%). ADR occurred with salicylates in 20/228 patients(8.8%), corresponding to 9/215 of mesalazine and 10/26 of salazopyrin treated patients, mostly gastrointestinal(GI) intolerance(n=8). ADR occurred in 78/207(37.7%) of thiopurine-treated patients; 5 had more than one ADR to thiopurines and 10 developed ADR despite change from azathioprine to 6-mercaptopurine. Reactions included myelosuppression(n=21), GI symptoms(n=20), pancreatitis(n=8). One case of corticosteroid ADR was reported (psychosis). 4/18(22,2%) methotrexate-treated patients experienced ADR, all liver toxicity. Infliximab-associated ADR occurred in 20/126 patients(6.1%), namely infusion reactions(n=7) or lupus-like syndrome(LLS) (n=6). 9/39 adalimumab-treated patients experienced ADR, such as skin rash(n=3). No reported ADR with ustekinumab or vedolizumab. Overall, ADR led to dose adjustments in 100/120 cases and to drug suspension in 22. Nine patients needed hospital admission and one died with squamous cell carcinoma in fistula tracts. 94.9% of these ADR remitted. In the univariate analysis, ADR were associated with IBD type(p=0.040), EIM(p=0.001), UC extent(p=0.016), thiopurine(p<0.001), infliximab(p<0.001) and adalimumab (p=0.005) exposure. In multivariate analysis, significance was kept with EIM(p=0.003), thioupurine(p=0.006) and infliximab(p=0.003) exposure. Patients who had one ADR, were not more likely to have ADR with other drugs.

Conclusion

ADR occurred in 28.7% of IBD patients and the most commonly implicated drugs were salazopyrin (10/26, 38.5% of patients) and thiopurines (75/207, 36.2%), rates much higher than those found with mesalazine and biologics. Nevertheless, most of these reactions resolved with dose adjustments or drug suspension, without hospital admission. This indicates that drugs available for IBD treatment remain safe, but their use must be cautious and toxicities should be monitored.
P464 Rac1/pSTAT3 expression in T lymphocytes: A potential pharmacodynamic marker for thiopurines in the treatment of Inflammatory Bowel Disease patients?
Authors: Deben D , Creemers R , Van Adrichem A , Drent R , Merry A , Leers M , Van Bodegraven A , Wong D
Published: January 2022

Background

The thiopurine derivatives, azathioprine (AZA), mercaptopurine (MP) and tioguanine (TG), remain standard treatment of Inflammatory Bowel Diseases (IBD). To date, therapeutic drug monitoring (TDM) is used to optimize thiopurine therapy. However, since this provides mainly pharmacokinetic information, TDM is of limited use to predict clinical effectiveness or to explain therapeutic failure. A specific pharmacodynamic marker would therefore be of more beneficial use. The immune suppressive mechanism of thiopurines, by the active thiopurine metabolite 6-thioguanine triphosphate, is primarily based on blocking the Ras-related C3 botulinum toxin substrate 1 (Rac1) causing T-cell apoptosis by inhibition of the phosphorylated downstream transcription factor signal transducer and activator of transcription 3 (pSTAT3) (Figure 1). The aim of this study was to explore whether expression of Rac1 and pSTAT3 in T-cells may be used as a pharmacodynamic marker for the therapeutic effect of thiopurine therapy in IBD patients.

Methods

To assess feasibility, T-cell Rac1 and pSTAT3 expression was evaluated in six parallel IBD groups: patients with active disease (1) and patients in remission on AZA/MP (2), TG (3), infliximab (IFX) (4), thiopurine and IFX (5) or without medication (6). Data of healthy subjects were used as reference values. Rac1 and pSTAT3 expression of patients in remission on AZA/MP or TG were compared to all other IBD groups and healthy subjects.

Results

Absolute Rac1 expression in T-cells did not differ between any of the IBD patient groups (Figure 2). A decrease in absolute pSTAT3 expression was found in IBD patients in remission on AZA/MP or TG, when compared to active disease patients, although not statistically significant. Notably, Rac1-corrected pSTAT3 expression was decreased in IBD patients in remission on AZA/MP or TG compared to active disease patients (p<0.01). This effect was not observed in the IBD groups in remission on other immunosuppressive therapy.

Conclusion

Rac1-corrected pSTAT3 expression in T-cells was significantly decreased in IBD patients in remission on thiopurine monotherapy compared to IBD patients with active disease, resulting in comparable values to healthy subjects. Rac1/pSTAT3 expression may serve as a potential, class specific pharmacodynamic marker to assess therapeutic efficacy of thiopurine monotherapy or as a marker to explain thiopurine resistance.
P471 Real-world experience of using Tofacitinib in Ulcerative Colitis in biologic naïve and biologic exposed patients
Authors: Cheesbrough J , Quraishi M N , Sharma N , Nassar I
Published: January 2022

Background

Tofacitinib is an oral, small molecule, which recently received NICE approval for the treatment of moderate to severe treatment refractory ulcerative colitis (UC). We present data on the regional experience for it use in relation to its efficacy in a cohort of patients with UC.

Methods

This study analysed a retrospective, cohort from a large IBD unit in the UK. Patients with UC commenced on tofacitinib between 2019 and 2021 for active disease were included. Clinical disease activity was assessed at baseline, week 8, week 16 and during follow up visits. We evaluated clinical response (>50% reduction in symptoms) at week 8, proportion of patients requiring extended of induction therapy to week 16 and need for re-escalation of maintenance dosing.

Results

A total of 55 patients were included (median age 34 years; IQR 15.75). Twenty six (47.3%) patients had pancolitis, 20 (36.4%) were biologic naïve and 18 (32.7%) were exposed to more than one biologic. Eighteen patients (32.7%) entered clinical response at week 8 and were able to de-escalate to 5mg BD maintenance therapy. Six patients (10.9%) had a primary non response and required a switch to an alternative biologic or a colectomy. Of the patients given an extended induction period (10mg BD for 16 weeks), 7/31 (22.6%) were able to de-escalate to 5mg BD, 15/31 (48.4%) continued on 10mg BD as maintenance and 9/31 (29.0%) discontinued treatment due to lack of clinical response. Of the patients on 5mg BD as maintenance 10/24 (41.6%) required re-escalation to 10mg BD maintenance dosing following a median duration of 10 weeks. Primary non response to tofacitinib were similar in biologic naïve patients compared to biologic exposed patients (25% vs 28.5% respectively). Biologic exposed patients were more likely to need 10mg BD as maintenance dosing compared to biologic naïve patients (72% vs 46.7% respectively).

Conclusion

Consistent with prior literature, our experience confirms the effectiveness of Tofacitinib in both biologic naive and biologic exposed patients with moderate to severe UC with similar clinical response between the two cohorts. Patients exposed to biologics however appear to have a greater likelihood of escalation to 10mg BD for maintenance therapy.