bluuebunny/crossref_metadata_2025 huggingface dataset:
P409 Non-invasive predictors of maintaining remission in patients with moderately to severely active Ulcerative Colitis treated with tofacitinib who dose-reduced from tofacitinib 10 mg twice daily to 5 mg twice daily: 6-month data from the double-blind, randomised RIVETING study
Authors: D’Haens G R , Dubinsky M C , Regueiro M , Santana G O , Torres J , Kulisek N , Gardiner S , Mundayat R , Paulissen J , Lawendy N , Su C , Modesto I , Sandborn W J
Published: May 2021

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). RIVETING (NCT03281304) is an ongoing, double-blind, randomised, parallel-group study designed to evaluate the efficacy and safety of dose reduction to tofacitinib 5 mg twice daily (BID) vs remaining on 10 mg BID in patients (pts) with UC in stable remission on tofacitinib 10 mg BID maintenance therapy. Eligible pts had received tofacitinib 10 mg BID for ≥2 consecutive years in an open-label, long-term extension study (NCT01470612), and had been in stable remission for ≥6 months and corticosteroid-free for ≥4 weeks prior to enrolment.1 We aimed to determine if faecal calprotectin (FCP), C-reactive protein (CRP) or partial Mayo score (PMS) can be used as predictors of maintaining remission after dose reduction.

Methods

Median FCP levels, median CRP levels and mean PMS at baseline (BL), Month 1 and Month 3 were analysed by efficacy endpoint status at Month 6 in pts who dose-reduced to tofacitinib 5 mg BID. The proportions of pts who achieved efficacy endpoints at Month 6 were analysed by stool frequency (SF) subscore, rectal bleeding (RB) subscore and modified PMS.

Results

Seventy pts were randomised to receive tofacitinib 5 mg BID in RIVETING. For pts in modified Mayo score remission at Month 6, PMS was relatively stable over time, whereas PMS increased from BL to Month 1 and Month 3 in pts not in modified Mayo score remission at Month 6; mean change from BL at Month 3 was 0.1 vs 0.7, respectively (Table 1). This trend was also observed for other efficacy endpoints (Table 1). Median FCP levels did not change from BL to Month 3 in pts who achieved Month 6 efficacy endpoints, whereas median FCP levels increased from BL to Month 3 in pts who did not achieve Month 6 efficacy endpoints (except remission) (Table 1). For all efficacy endpoints, no trend was observed in median CRP levels over time in pts who did and did not achieve Month 6 efficacy endpoints (Table 1).

A numerically higher proportion of pts with a SF subscore, RB subscore or modified PMS of 0 at Month 1 or Month 3 achieved efficacy endpoints at Month 6 compared with pts with respective subscores >0 (Table 2).

Conclusion

These analyses suggest that in pts previously in stable remission, an increase in FCP levels at Month 3, or PMS as early as Month 1, may help predict loss of efficacy after dose-reduction from tofacitinib 10 mg BID to 5 mg BID. A SF subscore, RB subscore or modified PMS of 0 at either Month 1 or Month 3 could indicate the likelihood of maintaining efficacy with tofacitinib 5 mg BID at Month 6. These analyses are post hoc, exploratory and limited by the small sample size.

Reference
P436 SPOSAB ABP 501 - A Sicilian Prospective Observational Study of Patients with Inflammatory Bowel Disease Treated with Adalimumab Biosimilar ABP 501
Authors: Macaluso F , Cappello M , Busacca A , Fries W , Viola A , Costantino G , Magnano A , Vinci E , Ferracane C , Privitera A C , Piccillo G , Belluardo N , Giangreco E , Romano C , Citrano M , Graziano F , Garufi S , Bertolami C , Scrivo B , Renna S , Casà A , Rizzuto G , Ventimiglia M , Orlando A
Published: May 2021

Background

Clinical data on the use of Adalimumab (ADA) biosimilar ABP 501 in inflammatory bowel disease (IBD) are lacking.

Methods

SPOSAB ABP 501 is a multicenter, observational, prospective study performed among the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). All consecutive patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) treated with ABP 501 from the introduction of the drug in Sicily (February 2019) to February 2020 (12 months) were enrolled. Patients were divided into 3 groups (group A: naive to ADA and naive to anti-TNFs; group B: naive to ADA and previously exposed to anti-TNFs; group C: switch from ADA originator to ABP 501). The primary end-point was the assessment of safety, in terms of rate of serious adverse events (SAEs). Secondary end-point was the evaluation of effectiveness, in terms of clinical response and steroid-free clinical remission at 12 weeks for group A and B, and as treatment persistency for all 3 groups.

Results

559 patients (median age 39 years; CD 88.0%, UC 12.0%) were included [group A: 189 (33.8%); group B: 30 (5.4%); group C: 340 (60.8]. Overall, the mean follow-up was 8.7 months (median 10.0 months, interquartile range: 6.0–12.0 months), and the total follow-up time was 403.4 patient-years. 36 SAEs occurred in 36 patients (6.4%), with an incidence rate of 8.9 per 100 person-years (PY), and 22 of them caused the withdrawal of the drug (incidence rate: 5.5 per 100 PY). The incidence rate of SAEs was higher among patients in group A compared with group C (17.4 vs. 4.8 per 100 PY; incidence rate ratio=3.61; p<0.001) and among patients in group B compared with group C (16.4 vs. 4.8 per 100 PY; incidence rate ratio=3.42; p=0.041). The effectiveness of ABP 501 after 12 weeks of treatment was assessed in patients naïve to ADA (group A + B; n=219): 188 patients (85.8%) had a clinical response, including 165 (75.3%) who achieved a steroid-free remission. Among the patients who responded at 12 weeks, a subsequent loss of response was reported in 17 subjects (9.0%). At the end of follow-up, 56 patients (10.0%) interrupted the treatment, with higher treatment persistency estimations for patients in group C compared with group A and B (log-rank p<0.001).

Conclusion

This is the first prospective study on the use of ADA biosimilar ABP 501 in IBD. Safety and effectiveness of ABP 501 seem to be overall similar to those reported for ADA originator. Switching from originator to ABP 501 was safe and effective.
P439 Effectiveness of Ustekinumab on Crohn’s disease associated spondyloartropathy: real-world data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)
Authors: Macaluso F , Fries W , Viola A , Costantino G , Muscianisi M , Cappello M , Guida L , Giuffrida E , Magnano A , Pluchino D , Ferracane C , Magrì G , Di Mitri R , Mocciaro F , Privitera A C , Camilleri S , Garufi S , Renna S , Casà A , Scrivo B , Ventimiglia M , Orlando A
Published: May 2021

Background

The efficacy of Ustekinumab (UST) on Crohn’s disease (CD) associated spondyloarthropathy (SpA) was evaluated neither in randomized controlled trials nor in real-world studies. Web-based data from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD) were extracted to perform a multicentre, real-world assessment of the effectiveness of UST on CD-associated SpA

Methods

All consecutive CD patients with active SpA at the initiation of the treatment with UST from January 2019 (the date on which the drug became available for clinical practice in Sicily) to August 2019 were extracted from the SN-IBD cohort. The study outcomes were evaluated at 8 and 24 weeks. The primary outcome was the articular response, defined as the disappearance of objective signs of arthritis (swelling and/or articular stiffness) and resolution of pain. As ancillary end-points, the clinical response (reduction of Harvey-Bradshaw Index ≥ 3 compared with baseline with a concomitant reduction of at least ≥ 50% of steroid dosage compared with baseline) and the steroid-free remission (Harvey-Bradshaw Index < 5 without steroids use) were assessed.

Results

Out of 131 total patients treated with UST, 30 consecutive patients (22.9%) had active SpA at baseline (axial SpA: 3/30; peripheral SpA: 18/30; axial plus peripheral SpA: 9/30). After 8 weeks, 10 patients (33.3%) reported an articular response [0/3 patients with axial SpA, 7/18 patients (38.9%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. After 24 weeks, 13 patients (43.3%) had an articular response [0/3 patients with axial SpA, 10/18 patients (55.5%) with peripheral SpA, and 3/9 patients (33.3%) with axial and peripheral SpA]. None of these 13 responders was taking systemic steroids at 24 weeks. The concomitant presence of a clinical response on intestinal symptoms was associated with the articular response at 24 weeks at univariable analysis (OR 5.14, CI 1.09-32.70, p=0.038).

Conclusion

UST obtained a response on articular symptoms in nearly half of the patients with CD and active SpA at baseline after 24 weeks. The rate of response was higher in case of peripheral arthropathy. The articular response was associated with the clinical response on intestinal symptoms.
P448 Safety of anti-TNF introduction following tuberculosis treatment in Inflammatory Bowel Disease patients in an endemic area
Authors: Azevedo M F C D , Justus F F , Lima C C G , Garcia K S , Barros L L , Oba J , Carlos A D S , Milani L R , Sipahi A M , Damião A O M C , Queiroz N S F
Published: May 2021

Background

Patients with inflammatory bowel diseases (IBD) have a greater risk of developing opportunistic infections, especially if they are under immunosuppressants and biological agents. Anti-tumor necrosis factor alpha (anti-TNF) has considerably increased the risk of tuberculosis (TB) in IBD patients. Brazil is considered an endemic area for TB and the safety of anti-TNF agents in IBD patients previous diagnosed with TB infection remains to be elucidated. The aim of this study was to evaluate the safety of anti-TNFs in patients with previous TB infection at a tertiary center in São Paulo, Brazil.

Methods

We retrospectively reviewed IBD patients with active TB followed in our center between January 2010 and December 2020. Data regarding disease phenotype, TB clinical presentation, IBD treatment at TB diagnosis and following TB treatment were collected from electronic medical records. TB diagnosis was based on symptoms, identification of the bacillus in body secretions, sample cultures, radiologic, endoscopic and histopathologic exams.

Results

Among 1040 IBD patients, we identified 37 patients with active TB (mean age at TB diagnosis 41.2 [25–69]; 59.4% male). Overall, 33 patients (89.2%) were under immunosuppressive medications. Of them, 27 (72.9%) were under anti-TNF drugs, 8 (29.6%) in monotherapy and 19 (70.3%) in combination with thiopurines or methotrexate. Pulmonary TB was the most common clinical presentation (40.5%) followed by disseminated TB (37.8%). Only 4 patients (10.8%) were not under immunosuppressant drugs and all of them were smokers. Sixteen (43.2%) patients received anti-TNF therapy after TB treatment, 4 of them had not been previously exposed to biologics. Median interval from TB diagnosis and anti-TNF initiation was 8 months (interquartile range [IQR] 4–24) and patients have been followed for a median of 34 months (IQR 7–108). Only one patient developed “de novo” tuberculosis, ten years after the first infection and after 48 months of treatment with infliximab and azathioprine.

Conclusion

Our findings suggest that treatment with anti-TNF following antituberculosis treatment is probably safe, even in endemic areas. TB occurred infrequently and after long-term follow-up, suggesting “de novo” infection rather than TB reactivation. This data emphasize the importance of periodic TB screening in IBD patients living in endemic areas.
P485 Development and implementation of a remote monitoring tool for real-world assessment of mild, moderate and severe infectious complications in Inflammatory Bowel Disease patients
Authors: Rezazadeh Ardabili A , Wintjens D S J , Mujagic Z , Cilissen M , Stassen L P S , Haans J J L , Jonkers D M A E , Pierik M J
Published: May 2021

Background

Immunomodulators and biologicals are cornerstones in the current management of Inflammatory Bowel Disease (IBD), but are associated with increased risk of infections. Post-marketing surveillance studies are important to assess the risk for infectious side effects in real-world populations, yet mainly focus on severe infections. Data on mild and moderate infections in IBD patients are scarce, primarily since self-limiting infections and infections treated by the general practitioner are not systematically captured in surveillance registries. Mild and moderate infections take longer to clear in immunosuppressed patients, have a large impact on (work) disability and quality of life, and potentially precede severe infections. In the current study, we aimed to develop and implement a remote monitoring tool for real-world assessment of infections in IBD patients.

Methods

Through a structured iterative process with input from IBD specialists, nurse practitioners, and a comprehensive literature review, a 7-item Questionnaire comprising 15 different types of infections (covering e.g. upper/lower respiratory tract; urinary tract; eye; and skin infections) was developed to measure Patient-Reported Infections (PRIQ) with a recall period of 3 months. Infection severity was defined as either mild (self-limiting or requiring topical/local treatment), moderate (requiring oral antibiotic, antiviral or antifungal drugs) or severe (requiring hospitalization and/or IV treatment). To ascertain comprehensiveness and comprehensibility in the intended study population prior to implementation, in three rounds a total of 36 randomly selected IBD patients visiting the outpatient clinic were interviewed individually until saturation was reached.

Results

Overall, patient understanding of the PRIQ was good and cognitive interviews did not result in reduction of questionnaire-items. Analysis of feedback from interviews resulted in addition of definitions to certain response options (e.g. definition for antivirals) and minor linguistic adjustments to further improve patient understanding. A total of three patients (8.3%) raised concerns on the recall period of 3 months, which after expert consensus, did not result in alteration of the recall period. Next, the PRIQ was digitized and implemented in myIBDcoach, an established telemedicine platform for management of IBD.

Conclusion

We developed a remote monitoring tool (PRIQ) to assess patient-reported infections in IBD and ascertained patient understanding through cognitive interviewing. A prospective multicentre study using the myIBDcoach platform is ongoing to validate the PRIQ and subsequently report the risk of mild and moderate infections across different treatment regimens in IBD patients (NCT04151420).
P500 Assessing physical activity, fatigue and quality of life in an outpatient cohort of IBD patients
Authors: Janssen L M , Hendrix E M B , Spooren C E G M , Stassen L P S , Pierik M J , Jonkers D M A E
Published: May 2021

Background

Inflammatory bowel disease (IBD) has a substantial impact on quality of life (QoL). This can further be affected by modifiable psychosocial and lifestyle factors, like physical activity (PA). In the current study, we aimed to determine whether PA activity levels were associated with patient and disease characteristics, fatigue and QoL in IBD patients.

Methods

In this cross-sectional study, consecutive adult IBD outpatients were included. PA was assessed by the Short QUestionnaire to ASsess Health-enhancing physical activity (SQUASH). Patients were considered to have adequate PA levels when exercising with moderate intensity during minimal 30 minutes for at least five days per week according to the Dutch Standards for Healthy Physical Activity. Body composition was assessed by body mass index (BMI) and fat-free mass using BodPod. Fatigue was measured with the Shortened Fatigue Questionnaire (SFQ) and QoL was determined using the SF-36. Patient and disease characteristics, fatigue, and QoL between patients with and without adequate PA levels were analyzed by a student’s t-test or X2-test when appropriate.

Results

Of the 200 patients (139 Crohn’s disease (CD), 61 ulcerative colitis (UC)), 53.3% were female, and 21.5% were active smoker. Mean disease duration was 11.4 [SD 9.9] years, and 28.6% had an exacerbation at inclusion. The Dutch Standards for Healthy Physical Activity were not met by 41.7%. CD patients (53.2%) were less likely to have adequate PA levels compared to UC (70.0%) patients (p=0.028). There were no other significant differences in patient and disease characteristics stratified by adequate PA level (i.e. sex, active smoking, age at inclusion, disease duration, Montreal classification, previous bowel resection, and disease activity). BMI and fat-free mass index were not associated with PA levels. However, patients not meeting PA standards were significantly more tired compared to patients meeting the standards (mean 17.4 [SD 7.0] vs. 13.5 [SD 7.2], p=0.015), and had lower physical and mental component scores (PCS: mean 43.5 [SD 9.7] vs. 46.0 [SD 8.5]; MCS: mean 46.2 [SD 11.3] vs. 52.3 [SD 9.5]) for QoL, reaching significance for SF-36 MCS (p=0.012).

Conclusion

IBD outpatients with low physical activity levels showed significantly higher fatigue and lower quality of life scores, regardless of disease characteristics. More research is necessary to identify contributing factors to further improve patients’ well-being by holistic management.
P521 Correlation between physician disease assessment in Ulcerative Colitis and burden of disease: ICONIC 2-year data of 120 patients in Turkey
Authors: Sezgin O , Atug O , Gonen C , Can G , Duman A E , Erzin Y Z , Yurci M A , Alkim C , Unal Ozcelik N G , Yildirim B , Kayacetin E , Beyazit Y , Tayfur Yurekli O , Kiyici M
Published: May 2021

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), and the overall burden is increasing at the global level. Differences in perceptions of UC-related burden may highlight dramatic degree insufficient patient-physician communication. ICONIC is a prospective, non-interventional, observational study assessing disease burden in adults with UC using Pictorial Representation of Illness and Self Measure (PRISM). The local results of ICONIC study for Turkey are presented.

Methods

Patients aged ≥18 years with early UC (diagnosed ≤36 months) were enrolled. At baseline and every 6 months, patient and physician reported outcomes were collected using PRISM, the Simple Clinical Colitis Activity Index (SCCAI and P-SCCAI), The Rating Form of IBD Patients’ Concerns (RFIPC), the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), and the Patient Health Questionnaire-9 (PHQ-9). Correlations between the patient assessed PRISM and other measurement tools were evaluated with Pearson correlation coefficient.

Results

One hundred and twenty patients were included (77 [64.2%] female; mean age 35.2 years). Physician-assessed disease severity was: severe 23 [19.2%], moderate 42 [35.0%], mild 40 [33.3%], in remission 15 [12.5%]. The mean ± SD physician- and patient-assessed PRISM scores were 4.8 ± 2.3 cm (range: 0.0–9.0) and 4.1 ± 2.6 cm (range: 0.0–8.5) at baseline and increased to 6.1 ± 2.3 cm (range: 0.1–8.5) and 5.5 ± 2.7 cm (range: 0.0–9.3) at the final visit, respectively, indicating an improvement in the perceived disease burden. The mean values of physician-SCCAI and P-SCCAI were 3.8 ± 3.5 and 5.5 ± 4.3 at baseline and decreased to 1.4 ± 2.5 and 2.7 ± 3.2 at the final visit, respectively, showing a decrease in disease activity. At baseline, the RFIPC and PHQ-9 values were 2.7 ± 1.7 and 8.0 ± 5.5 and decreased to 2.2 ± 2.0 and 5.2 ± 4.5 at the final visit, respectively. Patient-assessed SIBDQ was 43.8 ± 14.5 at baseline and increased to 54.0 ± 13.0 at the final visit. The strongest correlation of patient-assessed PRISM was with the physician-assessed PRISM (Spearman rho = 0.69, p<0.0001), followed by SCCAI (rho = -0.56, p<0.0001). Differences between physician- and patient-assessed PRISM scores were statistically significant (baseline: p=0.0010 vs. final visit: p=0.0206), highlighting an underestimation of patient’s suffering by physicians.

Conclusion

In the Turkish ICONIC sub-study, majority of patients on treatment showed improved outcomes during the follow-up period. A moderate correlation between patient-assessed PRISM and other measurement instruments represents that PRISM may be used as surrogate marker for patient suffering.
P555 Outcomes of multiswitching from original infliximab to biosimilars in patients with inflammatory bowel disease
Authors: Nascimento C , Revés J , Morão B , Frias Gomes C , Gouveia C , Palmela C , Roque Ramos L , Fidalgo C , Cravo M , Glória L , Torres J
Published: May 2021

Background

Since 2013 multiple Infliximab (IFX) biosimilars became available in the market. While there is evidence that switching from original IFX (RemicadeÒ) to an approved biosimilar product is safe and effective, little is known about outcomes of reverse switching and multiple switching among biosimilars in IBD patients. As the access to biosimilars at competitive prices increases, it is necessary to evaluate multiple switches to provide data on their interchangeability. Our aim was to evaluate the efficacy, safety and pharmacokinetic profile in a cohort of IBD patients who experienced multiple switches.

Methods

This is a cohort retrospective observational study, enrolling patients with IBD who were successively switched from original IFX to one or more biosimilars (multiswitching). We compared clinical disease activity, assessed using the Harvey-Bradshaw index (HBI) and partial Mayo Score (pMS), biochemical markers (hemoglobin, C-reactive protein (CRP) and albumin), IFX trough levels (ITL) and anti-IFX antibodies (ADA) immediately before and after multiswitching. Adverse and infusion-related events leading to drug discontinuation were registered.

Results

We included 26 patients (59% male, mean age 35±12 years), 85% (n=22) with Crohn’s Disease (CD) and 15% (n=4) with ulcerative colitis (UC) or indeterminate colitis. The mean disease duration from diagnosis was 9±6 years. According to Montreal classification, most patients were A2 (68%), had ileocolonic disease (L1 51%; L2 9%; L3 50%) and an inflammatory phenotype (B1 41%; B2 23% and B3 36%). Perianal disease was present in 44%. Half of patients had pancolitis (E3). About 51% of the patients had a prior resection surgery and 27% was on combination therapy when the first switch occurred. In 35% (n=9) of the patients three switches were observed. The mean follow-up from the first switch was 15±18 months. There was no significant difference in the proportion of patients in clinical remission (HBI < 5; Mayo score < 3) (91% vs 96%, p=NS). We found no differences in laboratory markers such as CRP (0,79 vs 0,67 mg/dl, p=NS), hemoglobin (13,83 vs 13,75g/dl, p=NS) and albumin (3,98 vs 4,37mg/dl, p=NS) before and after the multiswitching. No significant difference was observed in mean ITL (4,9 vs 4,05 μg/mL, p=NS) or in the proportion of patients with ITL>3ug/ml (p=0.205). None of patients developed ADA, infusion-related events or loss of response leading to drug discontinuation. During our follow-up none of patients was operated. Drug persistence was 100%.

Conclusion

In our cohort, no significant changes in efficacy, safety or immunogenicity were observed when IBD patients experienced multiple switches between the original IFX and its biosimilars.
P621 Lactose intolerance assessed by analysis of genetic polymorphism, breath test and symptoms in patients with inflammatory bowel disease
Authors: Nardone O M , Manfellotto F , D’Onofrio C , Rocco A , Annona G , Sasso F , De Luca P , Imperatore N , Testa A , de Sire R , Biffali E , Castiglione F
Published: May 2021

Background

Many patients with inflammatory bowel disease (IBD) make restriction of dairy products to control their symptoms. We aimed to investigate the prevalence of lactose intolerance assessed with hydrogen breath test (H-BT) in IBD patients in clinical remission with symptoms suggestive for lactose intolerance, compared to a sex- age- and BMI-matched control population. We further detected the prevalence of three single nucleotide polymorphisms of the lactase (LCT) gene: the lactase non persistence LCT-13910CC (genetic wildtype) and the intermediate phenotype LCT-22018AG, LCT-13910CT and we assess the correlation between genotype and H-BT

Methods

We performed a prospective study enrolling IBD patients in clinical remission: Crohn disease (CD) activity index CDAI<150 for CD and pMayo score≤1 for ulcerative colitis (UC) and controls. All of them underwent clinical evaluation, H-BT and genetic test analysing lactase gene polymorphisms located on chromosome 2. Statistical analysis was performed using chi-square, Student’s t-test and ANOVA.

Results

A total of 54 IBD patients and 69 matched controls were enrolled. H-BT was positive in 35(64.8%) IBD patients and 43 (62.3%) controls (p=0.3). No significant difference in lactose intolerance rate, assessed by H-BT and symptoms,was found between CD and UC patients (p =0.8). The wild-type genotype was found in 46 (85.2%) IBD patients , CT22018, AG13910 and CT22018/AG13910 polymorphisms were found in 9.3%, 1.8% and 3.7% respectively. While in the control group, the wild-type genotype, CT22018, AG13910 and CT22018/AG13910 polymorphisms were found in 87%, 5.8%, 5.8% and 1.4% of cases, respectively. The wild type and polymorphisms’ prevalence did not differ between IBD population and control group (85.2%vs 87%, p=0.1) (14.8% vs 13%, p=0.7) [Fig.1] and between CD and UC (p>0.05) [Fig.2]. The correlation between positive H-BT and genetic analysis showed that the wild-type genotype was associated with higher rate of lactose intolerance in the total population (OR 5.31, 95%CI 1.73–16.29, p=0.003) and in the IBD population (OR 7.61, 95%CI 1.36–42.7, p=0.02), even thought not in the control group (OR 4, 95%CI 0.90–17.68, p=0.07)

Fig.1

Fig.2

Conclusion

The prevalence of lactose intolerance in IBD is high but not dissimilar from that of the general population. The prevalence of the wild-type genotype in patients with IBD does not differ from the general population and it correlates with higher rate of lactose intolerance assessed with H-BT.

Despite suggestive symptoms, about 1/3 of IBD patients is not lactose intolerant, not needing elimination diet. These can lead to promote a rationale and balanced dietary management in IBD and thereby preventing the occurrence of calcium phosphate metabolism disorders.
P623 The impact of SARS-CoV-2 outbreak on the treatment adherence and clinical outcome of patients with inflammatory bowel disease treated with biological agents
Authors: Martino G , Carparelli S , Marseglia A , Pastore M R , Placentino M , Nardella M , Guerra M , Palmieri O , Latiano A , Perri F , Ercolino F , Bossa F
Published: May 2021

Background

The SARS-CoV-2 pandemic has led to a remodeling of care activity, including the inflammatory bowel disease (IBD) centers. According to international recommendations, we did not discontinue immunosuppressive or biologic drugs and reorganized biologic drug infusions’ administration to minimize the risk of infection. The aim of this study is to describe the clinical outcome of SARS-CoV-2 infection and the adherence to the scheduled biologic therapies in a single tertiary center including both IBD adult and pediatric patients treated with biological agents during COVID-19 pandemic.

Methods

Demographic information, clinical data and the adherence to the therapy were collected in all consecutive IBD patients treated with biologic agents from March 2020 to February 2021. Moreover, we reported the clinical outcome of IBD patients infected with SARS-CoV-2.

Results

A total of 278 subjects (171 male) treated with a biologic agent (34 children) were included. The mean age was 41.6 ± 17.3 years (range 5 – 88), and the mean disease duration was 12.7 ± 10.1 years (range 0.2 – 49). One hundred eleven patients (39.9 %) had ulcerative colitis, and 167 (60.0 %) had Crohn’s disease. About the therapy: 73 patients were receiving infliximab, 93 adalimumab, 20 golimumab, 59 vedolizumab, 29 ustekinumab, and 4 an experimental compound. 31 patient, including 1 child, (11.1 %) were treated with combination therapy. The mean Charlson Comorbidity Index was 1.5 (range 0 – 8). Twenty one patients (2 pediatrics and nineteen adults) (7.5 %) had a confirmed diagnosis of SARS-COV-2 infection. Only one of them (an adult man) was hospitalized but did not require intensive care unit measures. Compared to cumulative SARS-CoV-2 infection in the general population in our Region, the cumulative incidence of SARS-CoV-2 infection in our cohort was significantly higher (7.5% vs 4.0%, p < 0.002). Twelve adult patients (4.3%) postponed biologic therapy for fear of SARS-CoV-2 infection during the first wave of the pandemic, and two of them (16.6%) experienced a clinical relapse.

Conclusion

In our cohort, the adherence to biologic therapy was high during the pandemic, but the rate of clinical relapse in patients who postponed the scheduled administration of therapy was relevant. Although the incidence of SARS-CoV-2 infection was significantly higher than in general population, the clinical impact was mild as no patients experienced a severe form of COVID-19.
P629 Rural-urban inequities in Inflammatory Bowel Disease health care access: a population-based retrospective cohort study from a Western Canadian Province
Authors: Peña-Sánchez J N , Osei J A , Rohatinsky N , Lu X , Risling T , Boyd I , Wicks K , Quintin C L , Dickson A , Fowler S A
Published: May 2021

Background

Inflammatory bowel disease (IBD) is a chronic digestive condition with significant complications if left untreated. Rural dwellers face barriers to access specialised health care, which is located in larger urban centres. We aimed to contrast health care utilization (outpatient gastroenterology visits, colonoscopies, claims for IBD medications, IBD-specific and IBD-related hospitalizations, and surgeries for IBD) between rural and urban residents diagnosed with IBD in the Canadian province of Saskatchewan (SK).

Methods

We completed a population-based retrospective study using SK administrative health databases (hospital discharge abstracts, medication claims, and physician billings) between the 1999 to 2016 fiscal years. A validated IBD algorithm requiring multiple health care contacts was used for case ascertainment. IBD incidence cases were identified by requiring eight years of continuous health care coverage without IBD health care contacts before the date of diagnosis. Cases were assigned to a rural or urban location based on their residential postal codes at the date of IBD diagnosis. Study outcomes were measured from IBD diagnosis to the end of the study period or end of health care coverage. Cox proportional regression models were used to evaluate the associations between rural-urban residence and each study outcome. Models were adjusted by sex, age, neighbourhood income quintile at IBD diagnosis, and disease type (Crohn’s disease and ulcerative colitis). Adjusted hazard ratios (HR) and 95% confidence intervals (95%CI) were reported.

Results

We identified 5,173 IBD incident cases in SK between 1999 and 2016; 1,544 (29.8%) individuals were living in rural locations at the date of diagnosis. Compared to urban dwellers, rural residents had lower gastroenterology visits (HR=0.82, 95%CI 0.77–0.88) and higher 5-aminosalicylic acid (5-ASA) claims (HR=1.10, 95%CI 1.02–1.18). Furthermore, rural residents had a higher risk of IBD-specific (HR=1.23, 95%CI 1.13–1.34) and IBD-related (HR=1.20, 95%CI 1.11–1.31) hospitalizations than their urban counterparts. We did not observe significant rural-urban differences in the access to colonoscopies, biologic and immune modulator therapies, and surgeries for IBD.

Conclusion

We identified rural-urban disparities in IBD health care access, specifically, lower outpatient gastroenterology visits, higher 5-ASA claims, and a higher risk of hospitalizations for individuals living in rural locations at IBD diagnosis. Our findings reflect rural-urban inequities in the access to IBD care that require the attention of health care providers and decision-makers to promote health care innovation and equitable management of patients with IBD living in rural areas.
P642 Effects of Covid-19 on employment in IBD patients
Authors: Sciberras M , Nascimento C , Tabone T , Karmiris K , Nikolaou P , Theodoropoulou A , Mula A , Goren I , Yanai H , Amir H , Mantzaris G , Georgiadi T , Foteinogiannopoulou K , Koutroubakis I , Allocca M , Fiorino G , Furfaro F , Katsanos K H , Fousekis F , Michalopoulos G , Torres J , Ellul P
Published: May 2021

Background

There is an ongoing concern over the impact of COVID-19 on IBD patients. A significant proportion of IBD patients are treated with immunosuppressive medications and their effects on COVID-19 susceptibility and outcomes remain of concern to patients and physicians alike. Apart from the clinical outcome, the pandemic may have other psychosocial effects on this vulnerable cohort such as employment stability.

The primary aim of this study was to analyze the percentage of COVID-19 patients who tested themselves for COVID-19 and the outcome of those who tested positive. A secondary aim was to assess their employment status.

Methods

This was a multicentre international study whereby IBD patients (>18 years) in clinical remission over the last year, were asked to answer an anonymous questionnaire. Demographic data, type of IBD, current and previous medication, admissions to hospital, were collected.

Exclusion criteria included patients with IBD flares requiring corticosteroids in the previous 12 months.

Results

573 patients (CD: 55.5%) from 8 European Centres and Israel participated in the study. The mean patient age was 39.9 years (SD+/- 13.0). 21.6% were current smokers and 48.5% were non-smokers. The rest were ex-smokers.

44.5% (n=255 ) of patients were tested for Covid-19 and 5.1% (n=13) were positive. The majority were treated at home (92.3%) with only one patient requiring hospital admission. This was a 33 year old female smoker with UC (E3 disease activity) on anti-TNF therapy. 66.7% of positive cases were on anti-TNF medication and 22.2% were on thiopurines. None of the positive cases were on dual antiTNF/thiopurine therapy. 7.2% of patients had family members who also tested positive for Covid-19.

Almost half of all patients (45.2%) had their job affected during the pandemic and this was more prevalent in the UC cohort (P<0.05). 70% of patients switched to remote work from home and 21.4% became unemployed. The average age of patients becoming unemployed was 39.3years (SD+/- 11.9).

Conclusion

Nearly half of our cohort (45.2%) underwent testing and the majority (92.3%) were treated at home even though two thirds of them were on Anti-TNF medication. Unemployment rates affected 1 in 5 individuals and measures promoting remote work have been taken up wisely by IBD patients. Though the clinical outcomes were excellent, the psychological effects of unemployment have yet to be considered.
P651 Diagnostic delay, effectiveness and safety outcomes in a real-world cohort of patients with Crohn’s disease: data from administrative databases in Tuscany, Italy
Authors: Bertani L , Ferraro S , Bartolini C , Convertino I , Giometto S , Cappello E , Valdiserra G , Tillati S , Blandizzi C , Lucenteforte E , Gini R , Tuccori M , Costa F
Published: May 2021

Background

Diagnostic delay (DD) of Crohn’s disease (CD) is poorly investigated in the real-world setting, and could affect significantly the outcome of CD. The aim of the present study was to quantify the possible DD of CD in CD patients in Tuscany region of Italy, evaluating effectiveness and safety outcomes in CD patients with DD.

Methods

We conducted a retrospective cohort study on data extracted from administrative databases of Tuscany. We included patients >18 years old (yo) with a record of ICD-9 diagnosis for CD or disease exemption or a dispensation of oral budesonide from 6/1/2011 to 6/30/2016 (index date, ID) whichever came first. Patients with a look-back period (time before ID) < 5 y and follow-up (FUP) < 3 y were excluded. Patients with at least one Emergency Department (ED) access or hospitalisation for gastrointestinal causes in the lookback period (excluding 6 months before ID) could have a possible DD. DD was classified in short (up to 18 months) and long (up to 60 months). We performed survival analyses (Kaplan-Meier curves) for effectiveness (time free from the first: dispensation of azathioprine, biologic drug and ileocecal resection surgery) and safety outcomes (time free from first: ED access and/or hospitalization for any cause). Hazard ratio (HR) was calculated by using Cox models adjusted for age, gender and number of concomitant drugs in the month before ID. Both outcomes were evaluated for dichotomous (No DD and DD) and categorical variables of DD (No DD, short DD and long DD).

Results

Among 3342 CD patients, 584 (17,5%) had a suspected DD: 212 and 372 patients had short and long DD, respectively, p<0.001. The effectiveness analysis revealed that about the 20% of patients with long DD were treated with a biologic within 3 years, as compared with those with short DD or no DD (10%), p=0.0007. The adjusted (a)HR for biologic drug was 1.30 (Confidence Interval, CI 95%: 1.12–1.56) for patients with long DD and 1.02 (CI 95%:0.82–1.30) for those with short DD. No significant aHRs were found for the other effectiveness outcomes. The safety analysis showed that 75% of patients with DD had first ED access or hospitalization for any causes with the FUP, as compared with those without (about 60%), p<0.001. The aHR showed an increased risk for safety outcomes in patients with DD: 1.71 (CI 95%:1.61–1.91) for the ED accesses, 1.31 (CI 95%:1.19–1.49) for hospitalization, and 1.54 (CI 95%:1.41–1.71) for the composite outcome.

Conclusion

More than 17% of patients had a putative DD (mostly long DD). A risk of treatment with biologic drug, ED accesses and hospitalizations for any cause was found for patients with DD compared with those timely diagnosed.
P676 The small intestinal microbiome in Crohn’s disease is characterised by increased luminal diversity and stable mucosa-associated communities
Authors: Wauters L , Tito R , Ceulemans M , Moens A , Outtier A , Sabino J , Ferrante M , Vermeire S , Vanuytsel T , Raes J
Published: May 2021

Background

Crohn’s disease (CD) may affect the entire gut but the composition and optimal sampling of the small intestinal microbiome are understudied. We assessed the variation in small intestinal luminal and mucosal microbiota in CD compared to healthy volunteers (HV) and functional dyspepsia (FD) patients.

Methods

Duodenal biopsies were collected with the Brisbane aseptic biopsy device1 followed by sterile brushing of the lumen/mucus layer. Aseptic ileal biopsies and brushes were also collected in CD patients with synchronous lower endoscopy. Acid- (proton pump inhibitors, PPIs) or immune-suppression (IS) and macro- (erosions/ulcers) and/or microscopic inflammation (CD) were recorded. Contamination was minimised during sample and data processing2 with further analysis at genus level. Microbiota covariates were studied using distance-based redundancy analysis (dbRDA, genus-level Aitchison distance) and PERMANOVA. Alpha-diversity (α) was compared between sampling types (biopsy/brush), disease groups, PPIs (off/on), IS (yes/no) or location (CD). Genera abundance profiles were compared transversally (sampling type) and regionally (CD) with correction for multiple testing (FDR<.1).

Results

A total of 99 participants (21 CD, 48 FD and 30 HV) with similar demographics were included. Only sampling type and subject were associated with duodenal community variation (table). Transversal variation was also evident from the more significant clustering for sampling type vs. groups (fig 1). Within CD, sampling type (8.5%) and location (17.8%, both p=.005) but not treatment or inflammation were associated with community variation. Duodenal α-diversity of brushes was lower vs. biopsies (p<2*10–9) and higher in CD vs. controls (fig 2). Compared to untreated subjects, α-diversity was lower with PPI in brushes (fig 3) and higher with IS in biopsies (CD) (fig 4). The 42 differentially abundant genera between sampling types of the duodenum were largely shared between groups vs. only 3 different genera for the ileum (CD). In CD, regional differences were found for 24 genera in brushes vs. only 6 in biopsies, with inflammation driving minor changes in brush and not biopsy samples of the duodenum only.

Conclusion

Small intestinal microbiota variation is significant, especially between duodenal luminal and mucosal communities. Luminal α-diversity was highest in CD but lower than that of the mucosa with an effect of treatment. Despite regional variation, mucosal genera profiles were more conserved and less affected by inflammation in CD.

References

1. Shanahan et al., AP&T 2016

2. Davis et al., Microbiome 2018
P686 Novel grape-derived prebiotic selectively enhances abundance and metabolic activity of IBD and IBS faecal butyrate producing bacteria in an in vitro model of intestinal fermentation
Authors: Oliver L , Ramió-Pujol S , Amoedo J , Malagón M , Serrano M , Bahí A , Lluansí A , Busquets D , Pardo L , Serra-Pagès M , Aldeguer X , Garcia-Gil J
Published: May 2021

Background

Inflammatory Bowel Disease (IBD) and Irritable Bowel Syndrome (IBS) are two intestinal disorders with unknown aetiology. IBD presents two main forms which are Crohn’s disease (CD) and ulcerative colitis (UC). It has been reported recently that bacterial communities present in the colon of patients with either IBD or IBS are structurally different compared to those found in healthy individuals. This dysbiosis mainly consists of a decrease of butyrate producing bacteria and, therefore, the recovery of this metabolic group should be at the baseline of any successful treatment.

The main goal of this proof-of-concept study was to test the capacity of a new prebiotic of selected dietary fibre obtained from grape to balance the dysbiosis found in patients with different intestinal disorders.

Methods

In this study, fresh faecal samples from 6 healthy subjects, 3 CD, 3 UC, and 3 IBS were collected at the Hospital Universitari Dr. Josep Trueta. Fresh samples were diluted 1:5 with fermentation buffer and incubated with 200 mg of prebiotic at 37 ºC under agitation for 72 h. Results were compared with those obtained with various commercial prebiotics after simulating in vitro digestion: inulin, grape pectin, and grape seed extract (GSPE).

Total DNA was extracted and the abundance of butyrate-producing bacterial markers: F. prausnitzii (Fpra), its two phylogroups (PHGI and PHGII), Roseburia spp. (Ros) and S. variabile (Sva) was analysed by qPCR. Bacterial activity was determined by measuring short chain fatty acids (SCFA) concentration (butyrate, acetate, and propionate) by gas chromatography.

Results

The abundance of all butyrate-producing bacteria analysed increased after incubation with the new prebiotic. Among them, Ros presented significantly higher abundance values with respect to negative control in healthy, CU, and IBS patients. It also showed a significant increase in all individuals analysed compared to inulin, grape pectin, and GSPE.

Fermentation of the tested new prebiotic, produced significantly higher concentrations of SCFA (p < 0.001) when compared to negative control and all other commercial fibres. Acetate concentration was a 241% higher than negative control, followed by butyrate (187%), and propionate (169%).

Conclusion

The studied prebiotic produces in vitro an increase of the abundance and enhancement of the metabolism of butyrate-producing bacteria, when compared to commercial prebiotics. These results suggest that this new fibre is a promising prebiotic to be used in promotion of intestinal microbiota restoration at mucosa.
P687 Development of a panel of microbial markers to distinguish transient from pathological dysbiosis
Authors: Oliver L , Ramió-Pujol S , Malagón M , Serrano M , Bahí A , Busquets D , Torrealba L , Serra-Pagès M , Aldeguer X , Garcia-Gil J
Published: May 2021

Background

Dysbiosis is a widely used but unspecific term. It has been defined as any change in the composition of resident microbial communities relative to the ones found in healthy individuals. But it is still unclear which are the appropriate communities to define it and the reference values to measure it. Different studies have described dysbiosis in various diseases such as Inflammatory Bowel Disease (IBD), diabetes, rheumatoid arthritis, and autism, among others. Besides, the microbiota can be altered by transient factors such as antibiotics, diet, stress, or infections. Therefore, different degrees of severity can be associated with the term dysbiosis from which pathological and transient dysbiosis can be differentiated.

This work aimed at defining more specifically the term intestinal dysbiosis and to differentiate both transient and pathological dysbiosis.

Methods

Fifteen key microbial markers belonging to the principal families, classes and orders found in the human intestinal microbiota were accurately selected based on its functionality: F. prausnitzii (Fpra), E. coli (Eco), Firmicutes (Fir), Bacteroidetes (Bac), A. muciniphila (Akk), Ruminococcus sp. (Rum), Roseburia sp. (Ros), Gammaproteobacteria (Gam), Clostridia cluster I (Clo), Clostridia cluster XIV (XIV), Enterococcus sp., Lactobacillus sp. (Lac), C. albicans (Can), M. smithii (Msm), and the total bacterial load (Eub).

The dysbiosis was defined using stool samples in a cohort of healthy subjects (n=24) and then validated with 9 patients diagnosed with intestinal diseases 4 IBD and 2 Irritable Bowel Syndrome (IBS)). Total DNA was extracted and the abundance of microbial markers was analysed by qPCR.

Together with the establishment of the most common range in which each microbial marker was found, an index to define the pathological dysbiosis was calculated.

Results

Almost all healthy subjects analysed presented one or two slightly altered markers. The affected microbial markers in this “transient dysbiosis” were Fpra, Akk, and Ros, which are indicative of the mucous layer state, Firm as indicative of the lifestyle and fiber intake, Gam as characteristic of the pro-inflammatory state of the gut, and Msm as an altered intestinal habit and gas production.

All patients analyzed (IBD and IBS) presented alterations mainly of the bacteria inhabiting the mucosa and an alteration of the opportunistic species related to the disrupted mucous layer and defining “pathological dysbiosis”.

Conclusion

This study establishes an appropriate abundance range of key microbial markers in the gut, leading to a specific definition of dysbiosis which allows to differentiate the pathological from the transient dysbiosis. These results need further validation in a larger patient cohort.