bluuebunny/crossref_metadata_2025 huggingface dataset:
DOP47 Real World Evidence on the effectiveness of ustekinumab in Crohn’s Disease: Induction phase results from the prospective, observational RUN-CD Study
Authors: Bokemeyer B , Plachta-Danielzik S , Di Giuseppe R , Mohl W , Teich N , Hoffstadt M , Schweitzer A , von der Ohe M , Gauss A , Atreya R , Krause T , Blumenstein I , Höchstödter J , Hartmann P , Schreiber S
Published: May 2021

Background

Prospective, observational real world studies on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD) are required in addition to RCTs, usually confined to selected patients, which may not represent special treatment patterns and everyday clinical practice. The aim of the present 3-year RUN-CD study was to investigate the induction phase effectiveness of UST vs. other biologics (OB) in CD in terms of clinical and steroid-free remission at week 16. To the best of our knowledge, RUN-CD is currently the largest prospective real world evidence (RWE) study with UST in CD using propensity score adjustment.

Methods

Between 2017–2020, 901 CD-patients starting a new therapy with UST or OB, were enrolled in 44 IBD-experienced centers across Germany. After exclusion of missing outcomes, the final sample consisted of 657 patients. Clinical remission (HBI ≤ 4), and steroid-free remission (HBI ≤ 4 and no systemic use of steroids or budesonide during the last 8 weeks) were considered as outcomes at week 16. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI).

Results

339 UST (naïve: 34) and 318 OB CD-patients were included (ADA: 50.3%, IFX: 37.4%, VDZ: 12.3%) (naïve: 203). PS removed systematic differences between both groups (30.8% smokers, 15.1% perianal disease, 36.2% surgical resection, 40.5% EIM). The effectiveness of UST for clinical and steroid-free remission was comparable to that of OB at week 16. Besides, in bio-naïve patients, clinical remission was numerically, though not significantly, higher in UST vs OB (Table 1). Similar results were observed in the bio-experienced UST vs. OB groups [remission: 59.3% vs 55.4%; OR: 1.17 (0.73–1.90)]. For both the remission rates were higher in the bio-naïve than in the bio-experienced groups (p<0.05 for both).

Conclusion

In this prospective RUN-CD study, with propensity score weighted groups, UST showed similar induction effectiveness in comparison with OB therapies. Remarkably higher remission rates were observed in this RWE study than in prior RCTs. An additional favorable safety profile supports consideration of UST as a first-line targeted therapy for CD.
DOP65 Dietary therapy with the Crohn’s Disease exclusion diet induces sustained clinical and endoscopic remission in adults with Mild to Moderate Crohn’s Disease: Results from the CDED-AD trial
Authors: Yanai H , Levine A , Hirsch A , Sigall Boneh R , Kopylov U , Banai Eran H , Cohen N A , Ron Y , Goren I , Leibovitzh H , Wardi J , Zittan E , Ziv-Baran T , Abramas L , Fliss-Isakov N , Raykhel B , Pfeffer Gik T , Dotan I , Maharshak N
Published: May 2021

Background

Crohn’s disease exclusion diet (CDED) with partial enteral nutrition (PEN) is effective for induction of remission in children with mild-moderate Crohn’s disease (CD). Here we evaluated CDED in adults with CD.

Methods

This was an open-label prospective randomized controlled pilot trial in patients with mild-moderate CD defined as Harvey-Bradshaw Index (HBI) between 5–14, active disease on colonoscopy, or imaging with calprotectin>200 μ/gr. Group-I received CDED+PEN, and Group-II CDED-alone. A colonoscopy was performed at week-24. Endoscopic remission (ER) was defined as Simple Endoscopic Score for CD (SES-CD)≤3. The primary end-point was corticosteroid (CS) free remission defined as HBI<5 at week-6.

Results

Forty patients were included (median age 30 years [IQR;24–39], 19 patients- Group-I, 21 patients- Group-II). By intention-to-treat (ITT) analysis CS-free remission at week-6 was 62.5% of patients (25/40), comparable between Group-I 68.4%(13/19) vs.Group-II: 57.1%(12/21) (P=.46). Among remitters at week-6, sustained remission was present in 88%(22/25) week-12, and 80%(20/25) week-24. For patients with baseline elevated C-reactive protein (CRP) (n=30), median CRP decreased from 14.5 mg/L [IQR;7.7–37] to 8.4[IQR;5.4–18.5] at week6(P=.006), and to 8[IQR;5.4–20.6] week-24(P=.002). ER at week-24 was present in 14/28 patients (50%) and was 14/40(35%) by ITT. ER week-24 was similar between groups, 8/15(53.3%) vs. 6/13(46.1%) (P=.7). A comparison between baseline and week-24 SES-CD revealed a median of 5-points decrease (IQR; [-6.25]-[-1]), corresponding to 72.8% (IQR;20–100%) decline from baseline (P=.003).

Conclusion

CDED with or without PEN was effective for induction and maintenance of remission in adults with mild to moderate CD and may lead to endoscopic remission.
DOP75 Loss-of-response and immunogenicity following immunomodulator withdrawal from anti-tumour necrosis factor alpha combination therapy: Results from a large retrospective cohort study
Authors: Mahmoud R , Schultheiss J , Louwers J , van der Kaaij M , van Hellemondt B , Mahmmod N , van Boeckel P , Jharap B , Fidder H , Oldenburg B
Published: May 2021

Background

Combination therapy with anti-TNF compounds and immunomodulators (IMM; thiopurine or methotrexate) is superior to IMM or anti-TNF monotherapy in patients with inflammatory bowel disease (IBD). IMMs are frequently discontinued during the maintenance phase to mitigate the risk of adverse events, but long-term consequences of this practice are not well studied. We explored the real-world outcomes after IMM discontinuation, including loss-of-response (LOR), dose escalations, immunogenicity and trough levels.

Methods

This was a multicenter, retrospective cohort study in a general hospital and a tertiary referral center. We included adult patients with IBD, treated >4 months with infliximab (IFX) or adalimumab (ADA) and an IMM at baseline between 2011–2019. The IMM had to be started within 30 days of anti-TNF initiation, or continued for >30 days in case of prior IMM monotherapy. LOR was defined as anti-TNF discontinuation due to disease activity. Adjusted hazards rates (aHR) were calculated using mixed-effects Cox regression analysis with time-varying covariates, accounting for follow-up prior to and after IMM cessation. We adjusted for sex, age, BMI, smoking, Crohn’s disease (CD) vs ulcerative colitis (UC), disease duration, primary sclerosing cholangitis, rheumatological comorbidity, ADA vs IFX, and prior anti-TNF exposure.

Results

We included 615 episodes of combination therapy (543 individual patients; CD, n=382, 70%). The IMM was discontinued in 296 (48%) episodes after a median of 0.9 (IQR: 0.6 – 2.1) years, at which point 252 (85%) patients were in clinical remission. IMM withdrawal was performed as part of a de-escalation strategy (n=158, 53%), for intolerance (n=86, 29%) or for miscellaneous reasons (n=52, 18%). During a median follow-up of 1.7 (IQR 0.8 – 3.5) years after IMM withdrawal, 46 (16%) patients experienced LOR, 79 (32%) required dose-escalation and 31 (10.3%) developed anti-drug antibodies. Compared to IMM continuation, withdrawal did not significantly increase the risk of LOR (aHR 1.10, 95%CI: 0.74 – 1.64), but more patients required dose escalations (aHR 1.42, 95%CI 1.02 – 1.97) or developed anti-drug antibodies (aHR 2.22, 95%CI 1.21 – 4.08). Among patients who stopped the IMM, clinical remission at IMM withdrawal was the only predictor of LOR (aHR 0.48, 95%CI 0.23 – 0.99), while higher BMI (aHR 1.09, 95%CI 1.01 – 1.17) and shorter duration of combination therapy (Figure 1, aHR 0.57 per year, 95%CI 0.33 – 0.96) increased the risk of immunogenicity. IFX, but not ADA, trough levels decreased significantly after IMM withdrawal.

Conclusion

Withdrawal of immunomodulators is not associated with higher risk of LOR, but does increase the risk of dose-escalation and unfavorable pharmacokinetics.
DOP79 Primary hypogammaglobulinemia with IBD-like features: An ECCO CONFER Multicenter Case Series
Authors: Albshesh A , Eder P , Ribaldone D G , Oldenburg B , De Boer N K , Mantzaris G J , Savarino E V , Dragoni G , Weisshof R , Truyens M , Festa S , Maillard M H , Capirchio L , Filip R , Kopylov U
Published: May 2021

Background

The most commonly recognized clinical feature of hypogammaglobulinemia is recurrent infections with high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease (IBD).

Methods

This was a multicenter case series performed as a part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project.

Results

This report includes 25 patients with primary hypogammaglobinemia and IBD-like features [20 males and 5 females, mean age 50 years (±21.7 SD)]. Crohn’s disease-like features were noted in 22 patients, three patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinemia preceded IBD-like features diagnosis in 20 patients (mean of 7.7 years prior, range 0.3–35 years), and followed IBD-like features appearance in 5 cases (mean of one year after, 0.4- 9.1 years).

Hypogammaglobinemia etiologies were common variable immunodeficiency (72%), Agammaglobulinemia (8%), selective IgA-deficiency (8%), Goods syndrome (8%), IgG subclass deficiency with IgA deficiency (4%). In addition to antibiotics and intravenous immunoglobulin (IVIG) as a treatment for hypogammaglobinemia, fifteen patients received IBD treatment during the follow-up period, of whom two were on 5-aminosalicylic acid, five on corticosteroids, three on immunomodulatory, four on anti-tumor necrosis factor, and one on vedolizumab. By the end of the follow-up [35.5 months (Interquartile range 18–75)], 20 of 25 (80%) patients were in clinical remission.

Conclusion

This case series illustrates a strong male and CD-like features predilection. The diagnosis of IBD-like features mainly occurs after that of hypogammaglobulinemia, the majority of cases successfully recovered after appropriate treatment.
DOP86 Corticosteroid-sparing effects of ustekinumab therapy for Ulcerative Colitis through 3 years: UNIFI long-term extension
Authors: Scherl E J , Rowbotham D S , Danese S , Sandborn W J , Miao Y , Zhang H , Abreu M T , Panaccione R , Afif W , Hisamatsu T , Leong R W , Arasaradnam R P , Sands B E , Marano C
Published: May 2021

Background

Ustekinumab (UST) is an IL12/23 blocker approved for use in Crohn’s disease and ulcerative colitis (UC). In the UNIFI maintenance study of patients (pts) with moderate-severe UC, >90% of the pts who achieved clinical response or remission at week (wk) 44 were able to eliminate corticosteroids, an important goal of therapy. In this analysis, we describe the corticosteroid-sparing effects of UST treatment through 3 years among pts who were treated in the UNIFI long-term extension (LTE).

Methods

523 intravenous UST induction responders were randomized to SC maintenance therapy (SC placebo [PBO], n=175; UST 90mg every 12 wks [q12w], n=172; or UST 90mg q8w, n=176). 284 UST pts who completed wk44 entered the LTE. PBO pts were discontinued after wk44 unblinding. Based on the investigator’s clinical judgement of their UC disease activity, pts in the LTE were eligible to receive dose adjustment starting at wk56: PBO to q8w, q12w to q8w, and q8w to q8w (sham adjustment). Pts in PBO or q8w groups were only eligible for dose adjustment or sham dose adjustment before unblinding. Efficacy was evaluated in randomized pts using symptomatic remission (Mayo stool frequency subscore of 0 or 1 and a rectal bleeding subscore of 0).

During the maintenance study, all pts receiving corticosteroids at maintenance baseline were required to initiate tapering. Through wk152 of the LTE, symptomatic remission endpoints were calculated with treatment failure and missing data nonresponder imputation, and dose adjustment was not considered to be a treatment failure. Missing corticosteroid dose data was managed using last observation carried forward.

Results

Of the 284 pts in the randomized population who were treated with UST in the LTE, 139 were receiving corticosteroids at maintenance baseline. Of these, 91.4% (n=127) were no longer receiving corticosteroids at wk152. The average prednisone-equivalent corticosteroid dose among pts receiving corticosteroids at maintenance baseline in the q8w group was 15.4 mg/day at maintenance baseline and 1.7 mg/day at wks44 & 152. In the q12w group, average prednisone-equivalent doses were 15.4, 1.0, and 4.6 mg/day, respectively (Table 1). Corticosteroid-free symptomatic remission rates through wk152 are summarized in Table 2. Results were similar for the q8w and q12w maintenance doses. Of the UST-treated pts who were in symptomatic remission at wk152, 94.6% (88/93) in the q12w group and 98.0% (97/99) in the q8w group were corticosteroid-free.

Conclusion

UST maintenance therapy, with both q8w and q12w dosing regimens, was effective in reducing and eliminating the use of corticosteroids in pts with UC through 3 years. Through 3 years of treatment with UST, the majority of pts in symptomatic remission were corticosteroid free.
P134 Ultrasonographic scores for Crohn’s disease activity assessment – still lag behind CEUS
Authors: Freitas M , Macedo Silva V , Arieira C , Cúrdia Gonçalves T , Dias de Castro F , Leite S , Moreira M J , Cotter J
Published: May 2021

Background

Intestinal ultrasound (IUS) is an increasingly used non-invasive tool to monitor Crohn‘s disease (CD) activity. Currently, there is no widely accepted, reproducible IUS activity index to evaluate inflammatory activity. In 2020, two new scores emerged: the Simple Ultrasound Activity Score for CD (SUS-CD) and International Bowel Ultrasound Segmental Activity Score (IBUS-SAS). We aimed to compare the accuracy of SUS-CD, IBUS-SAS and contrast ultrasound (CEUS) in predicting inflammatory activity in the terminal ileum in ileocolonoscopy.

Methods

Retrospective study including all IBD patients submitted to conventional IUS and CEUS with contrast SonoVue® directed to the terminal ileum performed by a single operator between April 2016 and March 2020. Examinations were performed using an ultrasound Hitachi HI VISION Avius®. Qualitative and quantitative parameters from the conventional IUS analysis including wall thickness, stratification, colour Doppler and inflammatory fat were evaluated, and segmental SUS-CD and IBUS-SAS were calculated. A quantitative measurement of contrast bowel wall enhancement, peak intensity, was evaluated using CEUS. The CD activity was assessed with ileocolonoscopy by Simple Endoscopic Score for CD (SES-CD). Disease activity was graded as inactive (SES-CD<7) or active (SES-CD≥7).

Results

Fifty patients were included, 54.0% female, with mean age of 33±12years. Patients had a mean SUS-CD of 3.4±1.0, IBUS-SAS of 58.9±25.9 and CEUS peak intensity of 12.6±12.2. SUS-CD and IBUS-SAS were not different between patients with active or inactive disease (p=0.15; 0.57, respectively) with a poor capability to predict endoscopic activity (AUC 0.62, 95% CI 0.45–0.78; 0.55, 95% CI 0.38–0.72, respectively). Peak intensity in CEUS was significantly different in patients with active or inactive disease (p=0.004) with a good capability to predict endoscopic activity (AUC 0.80; 95% CI 0.64–0.92). A peak intensity optimal cut-off to predict active disease was 8.2 with a sensitivity of 71.4% and a specificity of 78.9%.

Conclusion

SUS-CD and IBUS-SAS were not able to predict with good accuracy endoscopic activity in terminal ileum in CD. On the other hand, CEUS with peak intensity assessment showed a good diagnostic accuracy for active inflammation in CD. Therefore, CEUS is a non-invasive emerging method, that should be routinely integrated in the ultrasonographic evaluation in CD.
P184 Disease activity in Inflammatory Bowel Disease patients is associated with increased liver fat content during follow-up
Authors: Van Lingen E , Tushuizen M , Steenhuis M , van Deynen T , Martens J , Diaz-Infante Morales D , van der Meulen-de Jong A , Molendijk I , van der Marel S , Maljaars J
Published: May 2021

Background

Increased liver steatosis is a frequently reported condition in patients with Inflammatory Bowel Disease (IBD). Different factors, both metabolic and IBD-associated, are believed to be contribute to the pathogenesis. The aim of our study was to calculate the prevalence of liver steatosis (LS) and fibrosis (LF) in IBD patients and evaluate which factors influence changes in steatosis and fibrosis during follow-up.

Methods

From June 2017 to February 2018, consecutive adult IBD patients were enrolled. Demographic and bio-chemical data were collected at baseline and after 6 to 12 months. The degree of LS and LF was assessed by transient elastography (Fibroscan). LS was defined as a Controlled Attenuation Parameter (CAP) ≥248, LF as a liver stiffness value (Emed) ≥7.3 kPa and IBD disease activity as C-reactive protein (CRP) ≥10 mg/l and/or fecal calprotectin (FCP) ≥150 μg/g. Changes in LS and LF were studied using ∆CAP and ∆Emed (follow-up minus baseline). An independent sample T-test was used to analyze the mean change in ∆CAP and ∆Emed. Univariate and multivariate linear regression analyses were performed, a P-value of ≤0.05 was considered significant.

Results

A total of 117 IBD patients were enrolled, of which 86 patients were also seen for follow-up. Of these 86 patients, 57% were male with a mean age of 43 (16.1) years. 48% of the patients suffered from Crohn’s disease. The mean Body Mass Index (BMI) was 25.0 (4.7) kg/m2 and 28 patients (33%) had an active episode of IBD at enrollment. The prevalence of LS at baseline was 39%, the prevalence of LF at baseline 13%. The mean change in ∆CAP was 22.44 (75.7) in patients with active disease at baseline and -34.1 (67.5) in patients in remission at baseline (p=0.001). The mean change in ∆Emed was 0.40 (1.9) in patients with active disease at baseline and -0.53 (2.7) in patients in remission at baseline (p=0.075).). Using a multivariate analysis, disease activity at baseline (B=37, 95%CI 6.38–67.61,P=0.018) and LS at baseline (B=-0.4, 95%CI -0.64 – -0.23,P=0.000) were associated with an increase in LS during follow-up. In univariate analyses, no factors associated with LF during follow-up were found.

Conclusion

Our study reveals a high prevalence of liver steatosis and liver fibrosis in IBD patients. Active IBD at baseline was associated with an increase in liver steatosis during follow up, but not with an increase in liver fibrosis.
P186 Inflammatory Bowel Disease Care in the Covid-19 pandemic era: Experience from a Tunisian gastroenterology department
Authors: Dahmani W , Sahar N , Aya H , Nour E , Wafa B A , Aida B S , Ahlem B , Mehdi K , Hanene J , Ali J
Published: May 2021

Background

The coronavarius disease (COVID-19) pandemic has brought forth a multitude of challenges for both patients having inflammatory bowel disease (IBD) and clinicians involved in their care. The national-wide lockdown in Tunisia, from Mars to Mai 2020 had substantially decreased healthcare accessibility and drugs availability. In addition, the uncertainty caused by the COVID-19 pandemic was likely to lead to anxiety and negative emotional and behavioral reactions which are thought to be predictors of active IBD and relapses.

We aimed to assess the hospital admission and complication rates in patients with IBD during the first wave of COIVD-19 infection in Tunisia and to compare them to those observed during the same period one year earlier.

Methods

We retrospectively analyzed the clinical features of patients with IBD admitted to our department during the period of time following the national lock-down in Tunisia ( from Mai, the 4th to August, the 31th). We compared the total global admission rate, IBD related complications, surgery rates and postoperative complications between the study period (P1) and the corresponding period of the previous year (P2 : from Mai, the 4th to August, the 31th, 2019). The Chi square test and Fisher exact test were used for analysis of categorical data.

Results

Eighty patients with IBD were included in this study (44 patients in P1 and 36 patients in P2), 73.7% of which (n=59) had Crohn disease. The sex ratio was 1.16 and the mean age was33.8 years ± 11.9. The mean follow-up period was 5 years. In 17.5% of cases (n=14), the IBD was diagnosed during the admission. None of the P1 patients had tested positive for SARS-CoV-2. The incidence of hospitalizations during P1 was 2.6 per week. It was greater than that of P2 but without the difference being statistically significant (2.1 admissions per week; incidence rate ratio: 0.34; 95% CI: 0.67-1.2; p = 0, 54). A total of 31 complications were noted (19 in P1 vs 12 in P2; p=0,489). The complications were as follows: 19 cases of acute severe colitis (12 in P1 vs 7 in P2 ; p= 0,234), 8 cases of intra-abdominal abscesses (6 in P1 vs 2 in P2 ; p=0,234), 4 cases of acute intestinal obstruction (1 in P1 vs 3 in P2 ; p=0,322). Among patients who had presented an acute severe colitis, 6 had undergone subtotal colectomy (6 in P1 vs 0 in P2, p=0,006).

Conclusion

Our study showed that during the pandemic period, there was an increase in the incidence of hospitalizations of patients with IBD as well as a significant increase in the need for surgery in severe acute colitis. These results should be taken into account so that IBD management strategies can be adjusted accordingly, if the COVID-19 pandemic persists or recurs, or in case of future outbreaks.
P232 Assessing effectiveness and patient perceptions of a novel electronic medical record for the management of inflammatory bowel disease
Authors: Kaazan P , Li T , Seow W , Bednarz J , Pipicella J , Ng W , Wiiliams A J , Connor S , Andrews J
Published: May 2021

Background

There is an increasing prevalence of chronic disease worldwide, resulting in multiple management challenges. Inflammatory bowel disease (IBD) is an exemplar chronic disease requiring optimal longitudinal coordinated care. We propose that Crohn’s Colitis Care (CCCare), a novel IBD-specific electronic medical record intended to improve IBD care is effective and acceptable to patients. We aimed to assess both the effectiveness of CCCare for data capture and patients’ acceptability of CCCare.

Methods

Methods:

The study was conducted at two tertiary Australian hospitals with dedicated IBD services: Royal Adelaide Hospital and Liverpool Hospital.

The effectiveness of CCCare was examined by comparing IBD-specific data completeness between pre-existing medical records and CCCare.

Acceptability was assessed with quantitative and qualitative feedback through the CCCare patient portal and with standardized paper-based questionnaires administered to a convenience sample of IBD clinic patients in two unmatched pre-CCCare and post-CCCare exposure cohorts. Descriptive statistics and multivariable regression models were applied to specifically examine overall ratings of CCCare acceptability using a 10-point numeric scale; factors associated with acceptability before exposure to the system and whether exposure or security concerns influenced its acceptability.

Results

In all 73 cases reviewed, there was data gain when using structured CCCare fields compared to IBD documentation in usual medical records.

Acceptability assessment through the patient portal feedback of 287 patients showed that the majority were very likely to recommend it to others (score, 8.56 ± 2.2 on a scale of 0–10). Common themes of concern among the 22 respondents with qualitative feedback were related to the novelty and limited experience of CCCare.

Study questionnaires indicated that the overall acceptability in the combined cohort (n=310) was very high (8.4 ± 2.1; scale of zero to ten) with more than three-quarters of patients rating acceptability as at least 8 out of 10. Self-reported information technology (IT) literacy was positively associated with acceptability. Exposure had a small positive affect on acceptability while the level security concerns had little impact on acceptability.

Conclusion

The IBD-specific electronic medical record CCCare is effective in facilitating enhanced completeness of IBD-specific data capture in comparison to pre-existing medical records. It is highly acceptable to patients, especially those with reasonable IT literacy. Patient concerns about privacy and security of EMRs did not significantly influence acceptability.
P321 Cessation of Anti-Tumour Necrosis Factor Therapy in Patients with Perianal Fistulizing Crohn’s Disease: Individual Patient Data Meta-Analysis of 323 patients from 12 studies
Authors: Ten Bokkel Huinink S , van der Woude J , Casanova M J , Bouguen G , Mak J W Y , Molnar T , Seidelin J , Aurelien A , D’Haens G , Riviere P , Guidi L , Renata B , Lin W C , de Vries A
Published: May 2021

Background

The risk of relapse after anti-tumour necrosis factor [TNF] therapy cessation in Crohn’s disease [CD] patients with perianal fistulas is unclear. We aimed to assess the risk of relapse after anti-TNF cessation in a large cohort and to identify risk factors.

Methods

A systemic literature search was conducted to identify cohort studies reporting on the incidence of relapse after cessation of anti-TNF therapy in CD patients. Individual patient data [IPD] were requested from the original study cohorts. Inclusion criteria for IPD-meta-analysis (IPD-MA) included age ³ 18 years, perianal fistulizing CD as indication for start of anti-TNF therapy, minimal treatment duration ³3 doses, and remission of luminal and perianal CD at cessation of anti-TNF therapy. Primary outcome was CD relapse [either perianal or luminal]. Perianal fistula relapse was defined as recurrence of draining perianal fistula related to previous or new fistula tracks, or abscess. Luminal relapse was defined as a clinical, biochemical, endoscopic, or radiological relapse requiring treatment or dose optimization of IBD medication or surgery. In a secondary analysis, risk factors associated with relapse were assessed using multivariate logistic regression analysis.

Results

A total of 307 patients from 12 studies in 9 countries were included in this IPD-MA. The median duration of anti-TNF treatment prior to therapy cessation was 14 months [IQR 6.1 – 29.9]. In 272/307 patients [89%] anti-TNF therapy was started for active perianal fistula and in 34 [11%] for both active perianal fistula and luminal CD. 169 patients [55%] developed a relapse [either perianal or luminal] after a median follow-up after cessation of 25 months [IQR 12 – 54]. Overall cumulative incidence of relapse was 31% and 43% at 1 and 2 years after anti-TNF cessation. Risk factor for CD relapse include upper GI involvement (L4) [HR 1.9], whereas older age [A3 vs A1, HR 0.48] and continuation of concomitant immunomodulators [HR 0.62] were protective factors. For a subgroup of patients with active perianal fistula and in luminal remission at start of anti-TNF, the cumulative incidence relapse rates were 25% and 43% at 1 and 2 years. No considerable differences in risk factors were found within this subgroup regarding risk of recurrence. Of the 179 patients who relapsed, 104 were retreated with anti-TNF with a response rate of 85%.

Conclusion

According to this IPD-MA, approximately two-thirds of CD patients with perianal fistula remain in remission with regard to fistulizing and luminal disease during 2 years after cessation of anti-TNF therapy. Further risk stratification based on perianal fistula characteristics is required.
P370 Concomitant azathioprine prevents new-onset arthralgia after initiation of vedolizumab: A retrospective cohort study
Authors: Kokkotis G , Zampeli E , Tzouvala M , Giotis I , Orfanos P , Benetou V , Stoupaki M , Gizis M , Kioulos N , Kitsou V , Leontidis N , Leonidakis G , Chatzinikolaou M L , Perlepe N , Koutsounas I , Lagiou P , Michopoulos S , Bamias G
Published: May 2021

Background

Vedolizumab is a monoclonal antibody against the gut-homing integrin α4β7 that is being used for the treatment of moderate to severe Ulcerative Colitis (UC) and Crohn’s Disease (CD). An increasing number of studies have reported new onset or reactivation of extra-intestinal manifestations (EIMs), among which arthralgia is the most prominent.

Methods

We aimed to study the incidence, characteristics and possible predictors of arthralgia development in patients under treatment with Vedolizumab, in a retrospective cohort study in 3 IBD centers in Athens, Greece. UC and CD patients treated with Vedolizumab (n=115, men=50.4%, UC=70.4%, median duration of follow-up=9 months) or Infliximab (n=93, men=69.9%, UC=29%, median duration of follow-up=29.1 months) were recruited. For each participant the entry point for the study was the first day of drug administration while the endpoint was either the day of arthralgia occurrence, the day of drug discontinuation or the day of the last interview if the patient was still receiving the drug. The SPSS-23 statistical program was used for analysis.

Results

Patients under Vedolizumab were at higher risk for new-onset (HR=4.76, P=0.001) and recurrent (HR=5.41, P=0.003) arthralgia compared to patients under Infliximab. New-onset arthralgia occurred in 20.9% while recurrent in 37.8% of 45 patients with a history of articular EIM. New-onset and recurrent arthralgias differed in certain characteristics. New-onset arthralgia involved peripheral joints in 91.7%, was milder, occurred shortly after Vedolizumab initiation (median drug exposure= 3 months, IQR=5 months) in patients in remission and remitted in 50% of cases. In multivariate Cox’s proportional-hazards model new-onset arthralgia was significantly associated with extensive colitis (HR=2.91, 95%CI=1.04-8.12). Of 15 patients with concomitant treatment of azathioprine no one manifested new-onset arthralgia (X2 P= 0.03, Fisher’s exact test P=0.038). Similarly, no patient with a history of appendectomy manifested new-onset arthralgia (n=12, X2 P= 0.067, Fisher’s exact test P=0.12). No predictors were identified for recurrent arthralgia. No patients discontinued vedolizumab due to arthralgia.

Conclusion

Vedolizumab treatment may be associated with the temporal manifestation of arthralgias. Patients under Vedolizumab with extensive ulcerative colitis have a higher risk of developing new-onset arthralgia, whereas, concomitant treatment with azathioprine and a history of appendectomy appears to have a prophylactic effect. This effect could be indicative of a distinct pathophysiological lymphocyte-mediated mechanism.
P378 Oxidative status and antioxidant capacity in children and adults with IBD: preliminary results of the OxIBDiet trial
Authors: Gatti S , Cianfruglia L , Galeazzi T , Palpacelli A , Quattrini S , Quatraccioni C , Catassi G , Monachesi C , Di Sario A , Armeni T , Catassi C
Published: May 2021

Background

Redox imbalance is involved in several aspects of inflammatory bowel disease (IBD). The OxIBDiet (NCT04513015) is a multicentre, 2-phases project involving IBD children and adults with the following aims: 1. To evaluate oxidative status of IBD subjects. 2. To estimate the effects of an antioxidant diet in IBD patients. Preliminary results are shown in this abstract.

Methods

The total antioxidant capacity, lipid peroxidation and the degree of protein oxidation were measured respectively through the ferric reducing ability of plasma (FRAP, µmol/equivalent FeSO4), serum levels of the thiobarbituric acid reactive substances (TBARs, µmol MDA) and advanced Oxidation Protein Products (AOPP, µmol/g protein). Reactive oxygen species (ROS, Arbitrary Units) and activities (nmol/min/mg of protein) of the main antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione S-Transferase (GST) and catalases (CAT) were evaluated in PMNs cells. Oxidative stress markers were correlated with demographic variables and clinical parameters.

Results

Fifteen adults (mean age: 36.2 ±11.4 years, 47% female, 67% in remission) and thirty five children (mean age: 14.13 ±2.2 years, 60% female, 65% in remission) with IBD have been enrolled so far. FRAP was significantly reduced in IBD children compared to healthy controls (median values: 212.1 vs. 248.3, p=0.0001) and to IBD adults (median value: 281, p<0.001), while no difference was observed between adults with IBD and the control group (p= 0.1). ROS levels did not differ in IBD children compared to adults and controls. The activity of GPX and CAT enzymes was increased in children with IBD in comparison to controls (p:0.02 and 0.001, respectively) while the activity of the other enzymes (GST, GR and SOD) and levels of lipid peroxidation and protein oxidation was not different between the 2 groups. Overall in the IBD group (children plus adults) FRAP was positively correlated with age (r=0.40, p=0.006), male gender (r=0.33, p=0.03) and use of biologics (r=0.47, p=0.001) and inversely correlated to disease activity based on clinical scores (r= -0.38, p=0.009). No correlation was found between FRAP and serum C-reactive protein or calprotectin levels.

Conclusion

The total antioxidant capacity (FRAP) is significantly impaired in IBD children respect to IBD adults and to healthy controls, thus suggesting an early involvement of oxidative stress in IBD pathogenesis. Moreover, the activity of the main antioxidant enzymes (GPx and CAT) in IBD children is increased, as a possible compensation for redox imbalance. Final results will clarify the involvement of antioxidant cascade in IBD pathogenesis and in therapeutic approach.
P383 Relationship between histo-endoscopic mucosal healing and baseline characteristics in patients with moderately to severely active Ulcerative Colitis receiving filgotinib in the phase 2b/3 SELECTION study
Authors: Peyrin-Biroulet L , Loftus Jr E V , Hibi T , Birchwood C , Yun C , Zhao S , Liu X , Rogler G , Danese S , Colombel J F , Feagan B
Published: May 2021

Background

Filgotinib (FIL), an oral preferential Janus kinase 1 inhibitor, was evaluated for the treatment of ulcerative colitis in the phase 2b/3 double-blind, placebo (PBO)-controlled SELECTION study (NCT02914522). Clinical, histological and endoscopic remission rates at week 58 were significantly greater with FIL 200 mg than with PBO (p < 0.025 for all comparisons). Here, we identify disease characteristics contributing to histo-endoscopic mucosal healing (HEMH; Geboes histological remission and endoscopic subscore ≤ 1) at week 58. FIL 100 mg data are excluded from by-treatment summaries because histological and endoscopic remission rates were not significantly different from PBO in SELECTION.

Methods

Eligible patients (18–75 years old) with moderately to severely active ulcerative colitis were enrolled in Induction Study A (biologic-naïve) or B (biologic-experienced) and randomized to receive FIL 200 mg, FIL 100 mg or PBO (2:2:1) once daily for up to 11 weeks, with response assessed at week 10. At week 11, FIL responders were re-randomized 2:1 to continue their induction FIL dose or to receive PBO for the 47-week maintenance study. PBO responders continued receiving PBO. For the maintenance study, univariate logistic regression was used to identify baseline and week 10 disease characteristics associated with HEMH (defined as achieving both Geboes histological remission [Grade 0 of ≤0.3, Grade 1 of ≤ 1.1, Grade 2a of ≤ 2A.3, Grade 2b of 2B.0, Grade 3 of 3.0, Grade 4 of 4.0, and Grade 5 of 5.0] and an endoscopic subscore of 0 or 1) at week 58 for patients receiving FIL 200 mg; variables with p < 0.05 in the univariate analysis were included in a multivariate analysis.

Results

Patients had similar characteristics across the treatment groups for both the induction (Table 1) and maintenance studies (Table 2). HEMH was achieved in a greater proportion of patients receiving FIL 200 mg than those receiving respective PBO at week 58 (32.7% vs 10.2%; p < 0.0001). No associations between disease characteristics (at baseline and week 11) and HEMH at week 58 were found (Table 3).

Conclusion

FIL 200 mg was effective at establishing HEMH compared with PBO at week 58; there were no baseline characteristics identified to be associated with HEMH at week 58.
P395 Impact of mirikizumab therapy on histologic measures of intestinal inflammation in a Phase 2 study of patients with moderately to severely active Crohn’s disease
Authors: Pai R , De Hertogh G , Reinisch W , Harpaz N , Feagan B , Agada N , Pollack P , Chan L S , Protic M , Magro F
Published: May 2021

Background

Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02891226) in patients with Crohn’s disease (CD). The histologic results at Week (W)12 induction and W52 maintenance are presented here.

Methods

Patients were randomized 2:1:1:2 across 4 treatment arms (PBO, 200, 600, 1000mg miri) administered intravenously (IV) every four weeks (Q4W) at Weeks 0, 4, and 8. Patients who received miri and achieved ≥1 point improvement from baseline (BL) at W12 in Simple Endoscopic Score for Crohn’s Disease (SES-CD) were re-randomized 1:1 into double-blind maintenance to continue their IV dose assignment Q4W (IV/IV) or to 300mg miri SC Q4W (IV/SC); maintenance IV arms were pooled for analysis. W12 non-improvers and all induction PBO patients received 1000mg miri Q4W from W12 through W52. Biopsies from terminal ileum and 4 colonic segments (ascending, transverse, descending, rectum) were obtained during endoscopy at W0, 12 and 52 and scored blind to treatment and response status. Ileum and colon scores were reported separately. Colon scores were derived from the sum of the 4 colonic segments, and total intestine scores from the 4 colonic segments plus ileum. Endpoints were defined post-hoc but prior to performing the analyses and only included patients with active histologic disease at BL (see Table). Histologic response was defined as: a) absence of neutrophils in lamina epithelialis, and absence of epithelial damage, erosions and ulceration or b) decrease of either RHI or GHAS ≥50% from BL. Histologic remission was defined as absence of mucosal neutrophils, epithelial damage, erosions, and ulceration. Deep histologic remission was defined as histologic remission combined with absence of chronic inflammatory cell infiltration of the lamina propria. For assessment of total intestine inflammation, the criteria for response, remission or deep remission must have been met in all 5 bowel segments.

Results

At W12, histologic response and remission were significantly higher in all segments of the 1000mg group versus PBO (response: ileum p<0.01, total intestine p<0.01, colon p<0.05; remission: ileum p<0.05, colon p<0.05, total intestine p<0.01). Among the W12 improvers, both histologic response and histologic remission at W52 were similar in ileum and colon in the IV/IV group, but lower in ileum than colon in the IV/SC group. All but 2 patients with remission at W52 were in deep histologic remission.

Conclusion

Patients treated with miri achieved and sustained histologic response and remission over 52 weeks of treatment. Among patients with W52 histologic remission, all but 2 patients achieved deep remission.
P397 Response to biologics in IBD patients assessed by Computerized image analysis of Probe Based Confocal Laser Endomicroscopy with molecular labeling
Authors: Iacucci M , Grisan E , Labarile N , Nardone O , Smith S C , Jeffery L , Ghosh S , Buda A
Published: May 2021

Background

The increase in therapeutic choices in inflammatory bowel diseases (IBD) imposed the identification of personalized therapeutic strategy. Confocal laser endomicroscopy (CLE) is a new endoscopic tool developed to obtain virtual in vivo histology. This study aimed to identify CLE in vivo and ex vivo features predictive of response for patients starting biologics.

Methods

We performed a prospective observational study at a single tertiary referral centre. 29 IBD patients (14 ulcerative colitis-UC and 15 Crohn’s Disease-CD) underwent colonoscopy with CLE before and 12-14 weeks after starting anti -TNF or 16 weeks after anti α4β7 integrin. CLE parameters analyzed were: crypt distribution along the mucosal surface, crypt area (CA), eccentricity, diameter, inter-cryptic distance (ICD), vessel tortuosity (VT), fluorescein leakage through the colonic mucosa (FLCM). Ex-vivo binding activity of fluorescein labelled biologics on corresponding biopsies was also assessed. Mosaicism reconstruction of CLE images were analyzed using a dedicated software algorithm (CellvizioViewer, Mauna Kea Technologies, ParisFrance). A dedicated Graphical User Interface was designed to enable a semiautomated analysis.

Results

After treatment, VT resulted significantly changed in overall IBD population (p<0.05), FLCM were reduced in UC patients (p<0.05), whilst CA, eccentricity and ICD decreased in CD patients (p< 0.05). The univariate regression analysis identified FLCM as the most accurate parameter for predicting responsiveness (AUROC) 83%, accuracy 83%, positive predictive value-PPV 94% and negative predictive value-NPV 57%). FLCM and ICD were the best discriminants in responders Vs non responders in UC patients (AUROC 85%, accuracy 85%, PPV 100% and NPV 71%); whilst VT, CA and ICD in CD patients (AUROC 95%, 86% and 83%; accuracy 90%, 90% and 88%; PPV 100%, 100% and 86%; and NPV 75%, 75% and 100%, respectively). Ex vivo confocal imaging revealed that UC patients, especially those responders, had higher basal fluorescent intensity signals with a significant reduction after biological treatment (p< 0.05), whereas in CD patients no significant change was found. An increased mucosal binding to the fluorescent labelled biological agent was associated to a higher likelihood of response to the treatment; this effect was higher in UC patients (AUROC 81%, accuracy 77%, PPV 100%, NPV 63%) compared to CD patients (AUROC 64%, accuracy 79%, PPV 80%, NPV 50%).

Conclusion

FLCM and ICD were the best discriminants of response in UC, while VT, CA and ICD in CD. A higher mucosal binding to a biological agent before treatment was observed in responders UC patients but not in CD patients.
P401 Risk of severe COVID-19 outcomes associated with inflammatory bowel disease medications: Reassuring insights from the United Kingdom PREPARE-IBD multicentre cohort study
Authors: Lamb C A , Sebastian S , Kent A J , Segal J P , Gonzalez H A , Brookes M J , Mehta S J , Subramanian S , Bhala N , Hicks L C , Conley T E , Patel K V , Walker G J , Kennedy N A
Published: May 2021

Background

During the early COVID-19 pandemic, the British Society of Gastroenterology (BSG) developed a risk stratification grid to inform the United Kingdom (UK) government regarding strict social isolation, termed “shielding”. This advised inflammatory bowel disease (IBD) patients thought to be most clinically vulnerable to SARS-CoV-2 infection or severe COVID-19 outcomes, to stay at home and minimize face to face contact, even with household members. Those considered at highest risk included recent commencement of combination biologic and immunomodulator therapy, prednisolone ≥20mg/day, presence of comorbidities, age ≥70 years or clinically active disease in those receiving immunosuppression. Mesalazine was not considered to increase risk. An acknowledged limitation was an absence of COVID-19 risk data. This study sought to identify patient or IBD medication-related factors associated with severe outcomes from COVID-19.

Methods

PREPARE-IBD was a multi-centre observational United Kingdom (UK) cohort study including adult IBD patients (≥18 years) diagnosed with COVID-19 by PCR between 1st March 2020 and 31st August 2020. The primary outcome was severe COVID-19 defined as requirement for intensive care admission, invasive ventilation or death. We tested associations of severe outcomes with medications and other covariates using multiple logistic regression.

Results

211 patients were included from 60 UK centres. 56 of 211 patients (26.5%) met the primary outcome. Severe COVID-19 was more common in ulcerative colitis relative to Crohn’s disease patients (33.9% [37/109] vs. 18.6% [16/86], p=0.018). Shortness of breath, nausea and vomiting were more common with severe COVID-19 (p<0.001 and p=0.023 respectively). Multivariable analysis identified co-morbidities and age as associated with severe COVID-19 outcomes; odds ratio (OR [95% CI]) 1.68 (1.23-2.35) for each co-morbidity, and an OR 1.03 (1.00-1.05) with each successive year of age. Neither clinically active IBD (OR 0.58 [0.26-1.26]), non-white ethnicity (OR 1.98 [0.92-4.28]), nor prednisolone use (OR 2.42 [0.47-11.26]) were associated with increased risk. On multivariable analysis, mesalazine was associated with severe COVID-19 outcomes (OR 2.03 [1.01-4.12]). Univariable analysis identified biologics and thiopurines as protective (OR 0.38 [0.15-0.87] and 0.32 [0.092-0.86] respectively). On multivariable analysis no association of severe COVID-19 outcomes with thiopurine or biologic exposure was seen.

Conclusion

Our data provide reassurance for the continued evidence-based use of corticosteroids, immunomodulators and biologic therapies in IBD during the ongoing COVID-19 pandemic, and is consistent with an as yet unexplained association between mesalazine use and severe COVID-19 outcomes.
P473 Ustekinumab and vedolizumab influence on cardiovascular risk factors in patients with Inflammatory Bowel Disease
Authors: Amiama Roig C , Suárez Ferrer C , Poza Cordón J , Rueda García J L , Sánchez Azofra M , Martín Arranz E , González Díaz I , Amor Costa C , García Ramírez L , Martín Arranz M D
Published: May 2021

Background

Chronic inﬂammatory diseases, including the Inflammatory Bowel Disease (IBD), show an increased risk in the development of atherosclerotic cardiovascular disease and coronary microvascular dysfunction at an early age.

AntiTNF α have proven to be effective in reducing the cardiovascular risk in these malaises, nevertheless due to their mechanism of action, we cannot determine whether such efficacy is due to an adequate inflammation control or due to the specific cytokine blockade, which plays an important role in both the inflammation and the atherogenic process.

Taking this into account, our hypothesis assesses whether using other anti-inflammatory therapies, such as Ustekinumab and Vedolizumab, would achieve a decrease in cardiovascular risk.

Methods

In this observational and retrospective study, we collected cardiovascular risk factors(CVRFs) in 46 patients, immediately before starting Ustekinumab or Vedolizumab and a year after, taking into account if patients were in clinical remission or not.

The CVRFs included were: body mass index (BMI), arterial hypertension, triglycerides values, lipid profile, albumin and C-reactive protein.

Results

46 patients were included, 33(71.74%) with Crohn and 13(28.26%) with Ulcerative Colitis. Of the total number of patients 25(54.35%) were treated with Ustekinumab and 21(45.65%) with Vedolizumab. During the follow-up, only one patient(0.02%) presented a new cardiovascular event.

Paired student’s t-test were used for data analysis in both treatment groups, comparing the values of the different CVRFs at the baseline and after one year of treatment. When comparing these values according to clinical remission at one year, no statistically significant differences were observed for any of them.

BMI and weight values were |24.49(DE 4.58) vs 24.93(DE 4.74) p=0,71| and |70.76kg(DE 13.86) vs 71.38kg(DE 13.33) p=0,85| respectively. As for hypertension, no relevant changes were observed, representing 15.22% of the population at the beginning and 17.39% after one year of treatment.

The differences observed in blood glucose values were|86.23(81.87–90.6)mg/dL vs 89.87mg/dL(84.72–95.01) p=0,27|. Regarding the lipid profile, the total cholesterol values were 158.58mg/dL(DE 36.5) and 168.69mg/dL(DE 32.72) p=0.18. HDL at the beginning 44.67mg/dL(DE 11.69) and after one year 47.43mg/dL(DE 10.19) p=0.28 and triglycerides values of 126.65mg/dL(DE 56.38) and 133.5mg/dL(DE 60.95) p=0,61. Albumin levels|4.08g/dL(DE 0.39) vs 4.27g/dL(DE 0.27)|did show significant differences (p=0,01).

Conclusion

Patients treated with Vedolizumab or Ustekinumab do not present a significative reduction in the cardiovascular risk after one year regardless of clinical remission.