bluuebunny/crossref_metadata_2025 huggingface dataset:
P278 Type IV collagen formation/degradation ratio predicts response to infliximab induction therapy in patients with Ulcerative Colitis
Authors: Bourgonje A R , Alexdottir M , Loveikyte R , Bay-Jensen A C , van Dullemen H M , Visschedijk M C , Festen E A M , Weersma R K , Karsdal M A , Faber K N , Mortensen J H , Dijkstra G
Published: May 2021

Background

Up to 50% of patients with ulcerative colitis (UC) do not respond to biological therapies, including TNF-α-antagonists (e.g., infliximab, IFX) and migration inhibitors (e.g., the α4β7-integrin inhibitor vedolizumab, VEDO). Therefore, serological biomarkers that predict therapy response are urgently needed. In this respect, biomarkers of extracellular matrix (ECM) remodeling, including basement membrane (BM) remodeling, and intestinal inflammation may hold promise as these processes play an important role in the pathophysiology of UC. In this study, we aimed to assess the predictive ability of serological biomarkers of ECM turnover and intestinal inflammation with regard to clinical response to IFX and VEDO therapy in patients with UC.

Methods

Serological biomarkers of collagen formation (PRO-C3, PRO-C4), matrix metalloproteinase (MMP)-mediated collagen degradation (reC1M, C3M, C4M, C4G, C6Ma3) and intestinal inflammation (macrophage activity marker [VICM] and calprotectin degradation fragments [CPa9-HNE]) were measured using neo-epitope solid-phase competitive enzyme-linked immunosorbent assay (ELISA) technology in 80 patients with UC who received either infliximab (IFX, n=26) or vedolizumab (VEDO, n=54) induction therapy. Clinical response to therapy was defined by composite assessment of available Simple Clinical Colitis Activity Index (SCCAI) scores and physician’s global assessments (PGA) derived from clinical records. Logistic regression modelling and receiver operating characteristics (ROC) statistics were used to assess discriminative capacity regarding response to IFX and VEDO.

Results

Only baseline ratios of type IV collagen formation and degradation (PRO-C4/C4M) were significantly elevated in patients with UC who clinically responded to IFX therapy (P<0.05). In addition, PRO-C4/C4M ratios accurately discriminated responders and non-responders to IFX therapy (area under the curve [AUC]=0.77, P<0.05), also after adjustment for confounding factors (AUC=0.88, P<0.01). Serum VICM levels were elevated in patients not responding to IFX therapy, but did not reach statistical significance (AUC=0.76, P=0.06). None of the biomarkers predicted response to VEDO therapy.

Conclusion

The baseline ratio of type IV collagen formation/degradation demonstrated high predictive accuracy with regard to response to IFX therapy in patients with UC, which may imply that patients with increased BM formation vs. degradation are more likely to respond. Furthermore, VICM may hold promise as a predictor for non-response to IFX therapy. Serological biomarkers of ECM turnover and intestinal inflammation may aid in predicting response to biological therapy and deserve validation in larger, prospective cohort studies.
P285 A retrospective observational study on the effectiveness and safety of vedolizumab with or without budesonide induction therapy among patients with moderate-to-severe Crohn’s disease
Authors: Weisshof R , Vavricka S , Pouillon L , Braegger F , Roset M , Bent-Ennakhil N , Ferrante M
Published: May 2021

Background

The α4β7 integrin monoclonal antibody vedolizumab (VDZ) has been shown to be efficacious for patients with moderate-to-severe Crohn’s disease (CD). This study aimed to analyse the added value of budesonide in combination with VDZ as an induction treatment for this indication.

Methods

A multicentre, retrospective chart review study was conducted in Belgium, Israel, and Switzerland. Adult patients with moderately to severely active CD (defined as an abdominal pain [AP] score of ≥2 and/or a mean daily loose stool frequency [LSF] score of ≥4 for the previous 7 days) who initiated induction therapy with either VDZ monotherapy (mono) or a combination therapy (combo) of VDZ with budesonide (index date) between 1 January 2015 and 31 January 2019 were included. Patients who received VDZ by IV infusion at weeks 0, 2, 6, 10 (only some patients received VDZ during week 10), and 8 weeks thereafter were assessed for time to patient-reported outcome (PRO) clinical remission (Kaplan-Meier curves), defined as an average daily composite score of AP ≤1 and LSF ≤31 within 14 weeks. Regression models were used to assess differences and associations.

Results

Overall, 123 patients were included (mono, n=73; combo, n=50). Patients initiating combo presented with more severe disease at index date than patients initiating mono. PRO clinical remission rates were estimated at 71.4% (50/70) in the mono and 68.0% (34/50) in the combo groups, with a similar median time to PRO remission of 91 days (95% CI: 70–98) and 95 days (95% CI: 70–98), respectively (Figure 1). Figure 2 shows the mean % change in AP and LSF from baseline to week 14, which was comparable for mono and combo. The variables associated with mean % change were moderate and severe AP scores for AP and being a current smoker for LSF. One patient in each group discontinued VDZ before week 14 (due to lack of effectiveness [mono] and adverse event [AE; combo]); 68.0% of patients in the combo group discontinued budesonide by the end of the follow up period. The reasons for discontinuation were routine treatment regimen (8 weeks 9 mg/day+subsequent tapering-off) in 85.3% of the patients, lack of effectiveness in 5.9% and AEs in 2.9% (5.8% other reasons). Safety event rates were similar among the groups for overall AEs (mono, 23.3%; combo, 26.0%), with the majority designated as mild to moderate in severity, and 83.3% resolved within the follow-up period.

Conclusion

Comparable effectiveness and safety outcomes were observed with mono and combo therapy in patients with CD; however, disease state among patients receiving combo was more refractory/severe at baseline. Further evidence is needed to corroborate these findings.

Reference
P290 Impact of concomitant 5-aminosalicylic acid therapy on vedolizumab efficacy and safety in Inflammatory Bowel Disease
Authors: Ungaro R , Kadali H , Zhang W , Adsul S , Reinisch W
Published: May 2021

Background

Vedolizumab (VDZ), a gut-selective anti-lymphocyte trafficking monoclonal anti-a4β7-integrin antibody, has showed efficacy in multiple phase 3 clinical trials in patients (pts) with inflammatory bowel disease (IBD). Decreased likelihood of response to adalimumab was previously observed with concomitant 5-ASA.1 This post-hoc analysis assessed the impact of concomitant 5-ASA on efficacy and safety in VDZ-treated pts with IBD.

Methods

Pts with IBD treated with VDZ intravenous (IV) or subcutaneous (SC) in phase 3 trials who continued 5-ASA (at any dose) at the time of starting VDZ were compared with those who received no concomitant 5-ASA. Pts were also stratified by ulcerative colitis (UC) or Crohn’s disease (CD). Efficacy outcomes were the proportion of pts achieving clinical response, clinical remission and corticosteroid (CS)-free clinical remission at Wk 6 (end of induction phase) and Wk 52 (end of maintenance phase). Safety outcomes were the proportion of pts experiencing any infection and enteric infections. Studies included: GEMINI 1 and 2, and VISIBLE 1 and 2 in efficacy analyses; GEMINI 1, 2, 3 and long-term safety for VDZ IV, and VISIBLE 1, 2, and open-label extension (data cut-off 17 May 2019) for VDZ SC in safety analyses.

Results

At Wk 6, clinical response was achieved by 191 (70.0%) and 69 (61.6%) VDZ-treated pts with UC with and without 5-ASA, respectively, and by 139 (64.4%) and 161 (57.7%) pts with CD, respectively (Table 1). At week 52, clinical remission was achieved by 134 (46.0%) and 45 (38.8%) VDZ-treated pts with UC with or without 5-ASA, and by 116 (50.2%) and 132 (37.5%) pts with CD, respectively. CS-free clinical remission at Wk 52 was achieved by 55 (34.8%) and 19 (37.3%) VDZ-treated pts with UC with and without 5-ASA, respectively, and by 46 (41.4%) and 46 (31.5%) pts with CD, respectively. Multivariate analysis in general showed no differences in VDZ efficacy with or without 5-ASA. No new safety issues or signals were identified. A tendency towards lower incidence of all infections and enteric infections was observed in pts receiving VDZ (IV or SC) with versus without 5-ASA (Table 2).

Conclusion

In this post-hoc analysis of VDZ pivotal trial data, concomitant 5-ASA does not appear to significantly impact the efficacy of VDZ in pts with IBD. No new safety signals were identified. The safety profile of VDZ IV and SC, with and without 5-ASA was consistent with the known safety profile of VDZ. Although there was limited data in some subgroups, there was no evidence to suggest that concomitant 5-ASA usage was associated with higher infection rates. These data will be useful to inform risk-benefit assessments of continued 5-ASA in VDZ-treated pts.

Reference
P318 Intra-dermal with topical imiquimod pre-treatment versus intra-muscular hepatitis B vaccination in inflammatory bowel disease patients: a double-blind randomized controlled trial
Authors: Ko K L , Lam Y F , Cheung K S , Hung F N , Leung W K
Published: May 2021

Background

Patients with inflammatory bowel disease (IBD) are often immunocompromised and at risk of various opportunistic infections including viral hepatitis. Vaccination is recommended to prevent hepatitis B infection, but efficacy with conventional intra-muscular hepatitis B vaccination in IBD patients is suboptimal. Intra-dermal vaccination has been shown to be an effective way in augmenting immune response in poor vaccine responders. In addition, topical imiquimod, a synthetic agonist of toll-like receptor 7, has been shown to further boost the immunogenicity when applied to the injection site before intra-dermal vaccination. Our study compared the efficacy of intra-dermal hepatitis B vaccination with topical imiquimod with conventional intra-muscular hepatitis B vaccination in IBD patients.

Methods

This is a double-blind, randomized-controlled trial. IBD patients with no evidence of active or past infection nor history of vaccination i.e. negative serology to all HBsAg/Anti-HBc/Anti-HBs were recruited. They were randomized in 1:1 ratio to receive either intra-dermal recombinant hepatitis B vaccine with topical imiquimod pre-treatment to site of injection (ID) or intra-muscular recombinant hepatitis B vaccine with topical aqueous cream (IM). Same dose (20mcg) of vaccine (Engerix B, Glaxo Smith Klein) was administered to both groups at 0, 1, 6 month. The primary outcome was the sero-protection rate at 12-month, defined as percentage of recruited subjects with anti-HBs titre ≥ 10 mIU/mL.

Results

104 patients (mean age 46; 68% male; 50% Crohn’s and 50% UC) were enrolled, with 53 received ID and 51 received IM vaccine. The percentage of patients using steroids, immunomulators and biologics at the time of randomization was 15, 55 and 22 %, respectively. Baseline demographic, disease characteristic, and laboratory parameter were comparable between the ID and IM groups. Sero-protection rate at 12-month was significantly higher in the ID arm compared to the IM arm (91% vs. 69%, P=0.005; Figure). Percentage of good responders at 12 month (anti-HBs titre > 100 mIU/mL) was also higher in the ID arm than in the IM (77% vs 59%, P=0.042). Multivariate analysis showed that use of ID vaccine (OR 4.45, 95% CI 1.40-14.47) and a higher albumin level (OR 1.30, 95% CI 1.06-1.58) are associated with better sero-protection rate. There was no significant difference in adverse effects reported in (64% in ID vs 55% in IM; Table).

Conclusion

ID hepatitis B vaccination with topical imiquimod is safe and offers superior seroprotection against hepatitis B among IBD patients.
P328 Ustekinumab is an effective and safe therapy in anti-TNF refractory Crohn’s Disease: a two year real-life observational study from Spain
Authors: Rueda Sanchez J , Cabello Ramirez M , Camara Baena S , Keco Huerga A , Garcia de la Borbolla Serres J , Castro Fernandez M , Grande Santamaria L
Published: May 2021

Background

Ustekinumab is a monoclonal antibody targeting IL-12/23 and was proved efficacious during the registration clinical trials. However real-world data in a day to day setting is still scarce. The aim of our study was to evaluate the effectiveness, durability and safety of ustekinumab in our real-life cohort.

Methods

We present a retrospective, observational study from a single tertiary center. We included adult CD patients that had received the standard ustekinumab intravenous induction and with at least 12-month follow-up. We assessed clinical (HBI) and biomarker (CRP, calprotectin) response at 3, 6, 12, 18 and 24 months. Adverse events, perianal disease response and corticosteroid (CS) use were also recorded.

Results

We observed a significant decrease in median HBI in all visits. Clinical response was observed in 72.7% of patients at 12 months and 66.7% at 24 months. Clinical remission was achieved in 57.6% and 58.3% of patients at 12 and 24 months respectively. CS-free clinical remission rates were 45.5% at 12 months and 54.2% at 24 months. The most frequent maintenance dose interval was q8w, with only 6/35 patients (17,14%) requiring dose escalation due to inefficacy of standard q8w interval. Drug survival at 2 years was 93.9%. Perianal disease clinical improvement was noted in 16 out of 17 patients with perianal disease at baseline. Fecal calprotectin decreased significantly from baseline, with a median change of -66 ug/g at 12 months and -253 ug/g at 24 months.

Ustekinumab was generally well-tolerated. Two adverse events were recorded during the follow-up period, an herpes zoster and an uveitis, none of them required Ustekinumab discontinuation.

Conclusion

According to our results, Ustekinumab was effective, durable, and safe for moderate-severe CD in a real-life clinical setting, with more than half of patients achieving CS-free clinical remission at 24 months in an anti-TNF refractory cohort.
P359 Influence of the nature of immunosuppressive therapy in patients with inflammatory bowel diseases on the level of immunoglobulins G after a Coronavirus Infection
Authors: Knyazev O , Kagramanova A , Lishchinskaya A , Noskova K , Chernova M , Shkurko T , Veselov A , Kulakov D , Li I , Parfenov A
Published: May 2021

Background

Currently, there are differences in the results of international studies and treatment outcomes in patients with inflammatory bowel disease (IBD) and COVID-19. Further research is needed to help answer the questions: do IBD patients have an increased risk of contracting SARS-CoV-2? Do IBD patients have more severe COVID-19 outcomes? Does IBD therapy increase the risk of infection? Do any IBD treatments protect against COVID-19?

Objective

To study the effect of immunosuppressors, genetically engineered biologics, and janus kinase blockers on the level of SARS-CoV-2 class G immunoglobulins in IBD patients who underwent COVID-19. .

Methods

The level of SARS-CoV-2 class G immunoglobulins was analyzed in 66 patients with IBD after COVID-19 infection. Male 28 (42.4%) of women 38 (57.6 per cent). The median age was 39±4.2 years. The duration of the anamnesis ranged from 1 to 8 years (Iu 4 years). The patients were divided into two groups, depending on the therapy performed: Group 1 (n=31) received long-term (more than 1 year) immunosuppressants (azathioprine/6-mercaptopurine/tofacitinib), group 2 (n=35) received anti-TNF-α therapy. The level of SARS-CoV-2 class G immunoglobulins was determined by the immunochemiluminescence method.

Results

After 4-6 weeks later, after a twice negative smear of PCR from the nose and oropharynx for SARS-CoV-2, in patients (n=31) receiving anti-relapse therapy with systemic IBD (azathioprine/6-mercaptopurine) and selective (tofacitinib) immunosuppressants, the average level of Ig G was 44.1±9.8 U/l. Among patients with IBD receiving anti-TNF-a drugs (n=35), the average level of class G immunoglobulins was 133.6±14.4 U/l. The difference was statistically significant (p=0.000003).

Conclusion

The level of class G immunoglobulins 3-4 weeks after the COVID-19 infection was significantly higher in IBD patients who received anti-TNF-α drugs.
P408 Anti-Drug Antibodies Detected in the Presence of Adequate Infliximab Drug Levels In IBD Patients in Clinical Remission have Limited Clinical Significance
Authors: Doherty J , Varley R , Healy M , Dunne C , Mac Carthy F , McKiernan S , Hartery K , Kevans D
Published: May 2021

Background

Immunogenicity, with the development of antibodies-to-infliximab (ATI) increases drug clearance and can lead to loss of infliximab (IFX) response in inflammatory bowel disease(IBD). Reporting of ATI is variable between commercial assays with some assays having high sensitivity for low-titre antibodies. Uniform thresholds for clinically relevant antibody titres are lacking. It is unclear how ATI affect treatment outcome when adequate trough IFX concentrations are present and ATI are detected.

Methods

We aimed to assess the impact of ATI detected in the presence of adequate IFX levels on the outcome of IFX therapy in IBD patients in clinical remission. A proactive therapeutic drug monitoring(TDM) strategy was utilized in our unit with IFX and ATI levels, assessed at trough, in all IBD patients receiving IFX. Baseline demographics were collected. Patients were grouped based on disease activity. An adequate trough IFX level was a concentration > 3 µg/mL, with low levels defined as < 3 µg/mL. ATI positivity was defined as a concentration > 10 AU/mL. Receiver operating characteristic analysis was performed to evaluate the classifying performance of ATI concentration for low IFX levels. Survival analysis was performed to determine IFX persistence in patients with adequate IFX levels and positive ATI. Follow up TDM assessments, where available, were documented to determine changes in ATI concentration over time in patients with adequate IFX levels.

Results

108 patients were included. Median age 36years. 46% were female. 36% had ulcerative colitis, 60% Crohn’s disease. 35% were receiving concomitant immunomodulators. 56% of patients were in remission at the time of TDM assessment. 44%, 30% and 26% of patients had IFX levels < 3 µg/mL, 3 – 7 µg/mL and > 7 µg/mL. Median [range] ATI concentration was 11 AU/mL [0 – 800]. ATI positivity occurred in 25%, 19% and 8% of IFX groups with levels < 3 µg/mL, 3 – 7 µg/mL and > 7 µg/mL. There was a weak inverse correlation between trough ATI and IFX concentration (p=0.01)(Figure 1). ATI concentration performed poorly as a classifier of low IFX levels (AUC 0.568)(p=0.39). 83%(15/18) of IBD patients in remission with adequate IFX levels and positive ATI remained on IFX for the duration of follow up with a mean cumulative time on IFX of 111.2 weeks (95% CI 105.1 – 117.3)(Figure 2). In this group, there was no significant change in ATI titre comparing index with follow up TDM assessments (p=0.14)(Figure 3).

Conclusion

ATI positivity in the presence of adequate IFX levels is common with proactive TDM. For patients in clinical remission ATI positivity in the presence of adequate IFX levels has limited clinical significance. Care should be taken to avoid unnecessary therapy alterations in this patient subgroup.
P428 Early and Late Fecal Calprotectin Remission - Analysis of a proactive Therapeutic Drug Monitoring Treatment Protocol
Authors: Pedro J , Rodrigues I , Damião F , Fernandes S , Gonçalves A R , Bernardo S , Baldaia C , Valente A , Moura Santos P , Correia L , Tato Marinho R
Published: May 2021

Background

Fecal calprotectin (Fc) is an adequate surrogate marker for endoscopic activity in inflammatory bowel disease. The timing of Fc remission may have prognostic implications in patients under biologic therapy.

Methods

Using a prospectively maintained database we followed 135 patients under a proactive therapeutic drug monitoring (pTDM) protocol aiming at an Infliximab trough level (IFXTL) between 5-10 µg/mL with sequential measurements of Fc. We evaluated the rates of early (at week 14) and late (after week 14) Fc remission (<250 µg/g) and associated clinical outcomes at 2-years of follow up.

Results

77 patients (57.0%) reached early Fc remission and 30 patients (22.2%) reached late Fc remission. Patients with late Fc remission presented higher Fc at baseline (1708.5 μg/g [681-3483] vs 803 μg/g [339-1477], P=0.006) and lower IFXTL at week 14 (2.71 µg/mL [1.24-6.30] vs 6.59 µg/mL [3.41-10.63], P=0.001) than patients with early Fc remission. However, by the end of follow-up, IFXTL were similar in both groups: 7.94 µg/mL (4.79-11.25) vs 8.54 µg/mL (6.49-11.07), P=0.514. In patients without early Fc remission, week 14 IFXTL did not differ between those with and without late Fc remission (2.71 µg/mL [1.24-6.30] vs 3.47 µg/mL [0.945-6.94], P=0.957), but significantly increased in late responders by the end of follow-up: 8.54 µg/mL (6.49-11.07) vs 4.37 µg/mL (1.77-7.49), P=0.002. Patients with early and late Fc remission presented similar rates of clinical remission (88.3% vs 83.0%, P=0.493), steroid-free clinical remission (79.1% vs 92.9% P=0.239), lower rates of IFX discontinuation (14.3% vs 16.7%, P=0.756), hospitalization (11.7% vs 13.3%, P=0.815), and surgery (1.3% vs 3.3%, P=0.485).

Conclusion

The magnitude of Fc at baseline and IFXTL at week 14 significantly influence the timing of Fc remission. The use of PTDM results in similar pharmacokinetics and clinical outcomes in both groups.
P429 Continued postoperative use of biologics for the prevention of recurrence of Crohn’s disease
Authors: Yu J , Hyun H K , Park J , Kang E A , Park S J , Park J J , Kim T I , Kim W H , Cheon J H
Published: May 2021

Background

Many patients with Crohn’s disease undergo major abdominal surgery during the disease course. Despite surgery, postoperative recurrence (POR) commonly occurs. Although postoperative use of biologic agents is known to be effective in preventing POR, few studies have evaluated the effectiveness of continuing the same biologic agents postoperatively in patients who received biologic agents preoperatively.

Methods

This retrospective observational study was performed in a single tertiary medical center. We retrospectively reviewed patients who underwent the first major abdominal surgery due to Crohn’s disease and divided them into two groups: biologics users both in the preoperative and postoperative periods and biologics users only in the preoperative period. We compared data between the groups according to endoscopic, clinical, and surgical recurrences.

Results

In total, 49 patients who used biologic agents preoperatively were recruited. Among them, biologics were used postoperatively in 24 patients (49.0%, Figure 1). Baseline characteristics except the median age and age at diagnosis were similar in both groups. Kaplan–Meier analysis revealed that the cumulative clinical recurrence rate was significantly lower in the postoperative biologics group (log-rank 0.012, Figure 2). On multivariate Cox regression analysis, postoperative biologics use was significantly associated with a decreased risk of clinical recurrence (adjusted hazard ratio 0.160, 95% confidence interval 0.037–0.692, p = 0.014).

Conclusion

Continuing biologics use postoperatively in patients who were receiving biologics preoperatively significantly reduced the rate of clinical recurrence. For patients with Crohn’s disease who were receiving biologic agents before surgery, continuing their use after surgery is recommended.
P462 Impact of teduglutide, a GLP-2 agonist, on inflammatory bowel disease-associated short bowel syndrome: a tertiary single-center study
Authors: de Seze M , Billiauws L , Bettolo J , Damas V , Hutinet C , Bonvalet F , Cazals-Hatem D , Villain C , Bouhnik Y , Joly F , Uzzan M
Published: May 2021

Background

Teduglutide (TED), a GLP2 agonist, have been shown to exert anti-inflammatory effects on the intestinal mucosa in murine preclinical models and evaluated with a positive trend in a phase 2a randomized controlled trial in non-short bowel syndrome (SBS) Crohn’s disease (CD) patients.

TED showed efficacy in reducing parenteral nutrition and or intravenous (PN/IV) dependence in SBS with intestinal failure (SBS-IF). However, limited data exists on its specific effect on the natural history of IBD in SBS patients treated with TED.

Therefore, we aimed to assess the efficacy and safety of TED in patients with IBD-associated SBS as well as the effect of TED on the course of IBD.

Methods

We conducted an observational retrospective study. Adult patients SBS-IF due to IBD and who were treated with TED were enrolled. Response was defined as a decrease of at least 20% in total volume of PN. Active IBD was defined based on morphologic and histologic data (CT-scan, colonoscopy and/or enteroMRI). Patients were followed until last news or TED discontinuation.

Results

We enrolled 14 IBD patients, including 2 patients with ulcerative colitis, with a median follow-up of 4.2 ± 4 years. Of the 12 CD patients, 11 had ileocolonic involvement and 1 had only small bowel involvement. 11 patients had type-1 SBS and 3 had type-2 SBS. 7 patients were only receiving intravenous fluid and 7 were on PN/IV. Patients were in average receiving PN/IV for 9.1 years at TED initiation.

Regarding IBD, 4 patients had active disease at inclusion, 3 with a structuring behavior and 1 with a fistulizing behavior. 5 patients were on biologic treatment (antiTNF or ustekinumab) at inclusion.

At month 3 (M3), 9 of 14 patients were responders. 3 were weaned from any iv supplementation. 3 of 7 patients initially on TPN were weaned from caloric input, including one still receiving iv fluids. Caloric input was in average at 7330 kcal/week at baseline versus 4615 at M3. Mean total parenteral volume went from 11849

ml/week at M0 to 8223 at M3.

2 of 4 patients with active disease at baseline showed improvement in disease activity while on TED. The latter 2 patients were totally weaned off PN/IV.Six patients withdrew TED during follow-up. 2 patients stopped after a diagnosis of cancer (1 melanoma and 1 chronic myeloid leukemia). Survival without TED discontinuation was estimated at 85.7 % IC95(69.2–100) at 1 year, 78.6% IC95(59.8–100) at 2 years and at 64.3% IC95(43.5–95) at 5 years

Conclusion

TED appears effective and safe in IBD-associated SBS-IF patients. In specific cases, it may impact positively the inflammatory course of the disease. Further prospective studies are warranted to specifically evaluate TED in IBD-associated SBS, including patients with active IBD.
P468 Analysis of international spontaneous reporting system databases for safety of corticosteroids in Inflammatory Bowel Disease: The Determinants, Incidence and consequences of Corticosteroid Excess (DICE)-impact study
Authors: Raine T , Bokemeyer B , Finney-Hayward T , Munsaka M , Liu M , Louis E
Published: May 2021

Background

Long-term use of corticosteroids (CS) may result in significant risk of adverse events (AEs), and the true incidence of AEs in patients with inflammatory bowel disease (IBD) receiving CS is unknown.1 Such AE data may be reported in spontaneous reporting systems (SRS). Using data-mining algorithms for disproportionality, we determined the frequency of AEs of special interest (AESIs) associated with CS in patients with IBD.

Methods

The FDA SRS database (FAERS) was examined for AE reports associated with prednisone/prednisolone (PRED) or budesonide (BUD) use for Crohn’s disease or ulcerative colitis from Q1 2008 to Q4 2019. The incidence of key predefined AESIs was determined and the association with CS therapy was assessed using the proportional reporting ratio (PRR) criteria.

Results

Totals of 420,913 and 33,215 all-cause AEs were reported for PRED and BUD, respectively. The number of AE reports for each CS increased over time (Figure 1) and this was reflected in an increase in the proportion of reports of all AEs over time relating to CS. Common AEs reported with CS therapy included diarrhoea, abdominal pain, pyrexia and weight loss (Figure 2). Compared with other drugs and based on the PRR criteria, AESIs including osteonecrosis, adrenal insufficiency and Cushingoid complications were more frequently reported in patients treated with PRED; adrenal insufficiency, pancreatitis and Cushingoid complications were more frequently reported in patients treated with BUD (Table 1). There was no confounding effect from gender or disease type identified between CS and any of the AESIs in patients with IBD.

Conclusion

Analysis of FAERS demonstrated that steroid-treated patients with IBD report AEs that are consistent with the known safety profile for CS. Cushingoid complications and adrenal insufficiency were common signals for PRED and BUD. The increased reporting of AEs over time may reflect growth in CS prescribing, or growing awareness and reporting of CS AEs by prescribers. This analysis will be repeated in multiple international SRS systems to provide a global image of AEs for CS use in IBD.

Reference
P474 Postoperative infectious complications in patients with Inflammatory Bowel Disease: experience of a tertiary center
Authors: Librero Jiménez M , Ortega Suazo E J , Sánchez Capilla A D
Published: May 2021

Background

Patients with Inflammatory Bowel Disease (IBD) are at increased risk of postoperative infectious complications (PIC). There are few studies and conflicting data regarding the risk factors involved in these patients. The aim of this study was to investigate the incidence of infectious complications and postoperative mortality in patients with IBD who underwent intestinal surgery, as well as describe the characteristics of our population and identify possible risk factors.

Methods

Retrospective study on patients with Inflammatory Bowel Disease (Crohn’s disease (CD) and Ulcerative Colitis (UC)) treated in “Virgen de las Nieves” University Hospital between January 2019 and December 2020. Patients who underwent small bowel or colorectal surgery were included. Information regarding demographic and clinical data, procedures, treatments and surgical outcomes were collected. Clinical outcomes documented were postoperative infectious complications and in-hospital mortality. Descriptive inferential were carried out.

Results

36 patients were included (47.2% male, median age 44.9 years). All the characteristics of our sample are detailed in Figures 1 and 2. Regarding surgical outcomes, 7 patients developed PIC (6 surgical site infection (SSI) and 1 multiple infections including pneumonia, candidemia and SSI). The features of these patients are detailed in Figures 3 and 4.

Conclusion

Postoperative infectious complications after intestinal surgery are an important cause of morbi-mortality in CD and UC patients. Identifying risk factors early, could help reduce the incidence of these complications.

Seven patients (19,4%) in our sample developed PIC, mostly SSI. All of them diagnosed of CD, which explains the greater need of surgery in them compared to patients with UC. These patients had more severe disease: penetrating pattern (B3 according to Montreal Classification) and ileocolonic location (L3). Most patients were receiving immunosuppressive treatments by the time of surgery, especially biological treatments. The median time of evolution of the disease was high, describing a profile of disease more advanced.

Our efforts should be determined to early prevention and treatment of modifiable risk factors during the perioperative period. In order to achieve this aim, further research is needed, with prospective, multicenter and wider population studies, trying to control any confusion factors. Finally, we would like to highlight the need of studies analyzing UC population, as most of them focus on patients with CD.
P490 The impact of the COVID-19 pandemic on gastroenterologists providing care to inflammatory bowel disease patients in Canada: preliminary data of a cross-sectional survey
Authors: Mikail M , Malhi G , Wilson A , Khanna R
Published: May 2021

Background

We aim to explore the impact of COVID-19 pandemic-related restrictions on gastroenterologists providing care to inflammatory bowel disease (IBD) patients in Canada.

Methods

We invited 28 Canadian gastroenterology societies, 14 academic centres and 101 community hospitals and private clinics to have their gastroenterologists engage in an online mixed methods survey from December 2020 - March 2021. The survey explored the impact of pandemic-related restrictions on gastroenterologists managing IBD patients and the impact on clinical decision-making, rates of consultation, investigations and endoscopies conducted before and during the pandemic.

Results

59 gastroenterologists (59.3% male) participated in our study with 40.7% having completed additional training in IBD. Respondents mean age was 43.7 years with 30.5% practising independently for a duration of less than or equal to 5 years. The majority of respondents were from Ontario (43.1%), Quebec (31%) and British Columbia (13.8%) with 62.7% practising primarily at an academic centre.

93.2% of respondents reported that their practice was affected by the pandemic. 44.6% note a reduction in the number of total consultations completed. Only 60% were able to arrange endoscopies for patients in an active IBD flare at an appropriate time interval compared to their pre-COVID practice. During the pandemic, 87.3% reported a reduction in the total endoscopies performed, with 43.8% of those individuals noting a minimum reduction of 25% of previous volumes. The following barriers attributed to the decrease in endoscopies performed during the pandemic: institutional-imposed restriction on daily allowed endoscopies (97.9%), indication for endoscopy was non-urgent (68.8%) and patient-requested cancellation due to a fear of contracting COVID-19 (87.5%).

63.6% of respondents were able to arrange outpatient laboratory investigations in less than 1-week prior to the pandemic vs. 41.8% arranging similar tests in 1–2 weeks during the pandemic. 50.9% were able to arrange diagnostic investigations in 1–2 months before the pandemic vs. 65% arranging similar tests in 3-months or more during the pandemic.

When advancing drug therapy in IBD patients before versus during the pandemic, respondents reported the following factors as playing a crucial role in clinical decision making: patient symptomatology (87% vs. 79.3%), laboratory investigations (94.8% vs. 96.6%), diagnostic imaging (89.7% vs. 81%) and endoscopy findings (89.7% vs 72.4%).

Conclusion

We illustrate that Canadian gastroenterologists have been affected by the pandemic, with decreases in endoscopy performance related to access and patient preference and less decision-making guided by endoscopy. Outpatient access to urgent investigations was reduced.
P501 Incidence and therapeutic management/treatment of very early onset inflammatory bowel disease during 2015–2020
Authors: Ninh G , Wewer V , Jakobsen C
Published: May 2021

Background

To investigate the incidence of very early onset inflammatory bowel disease (VEO-IBD) in a cohort representing two regions in Denmark during the period 2015–2019 and to assess the medical and surgical treatment.

Methods

All patients diagnosed with VEO-IBD within The Capital Region and The Zealand Region from January 1, 2015 to July 1, 2020 were included. Demographic and clinical data and medical and surgical treatment were extracted from the files.

Results

Forty patients with VEO-IBD were identified. The incidence rate was 2.0/100,000 (CI 95% 0.8–5.9) during the 2015–2019. Totally 35 patients (87.5%) received immunomodulatory therapy during follow-up. The cumulative risk of receiving immunomodulatory therapy after 1 year, 3 years and 5 years was 58% (95% CI 39–71), 88% (95% CI 70–95) and 91% (95% CI 73–97) respectively. Totally 23 patients (57.5%) received biological therapy. The cumulative risk of receiving biological therapy after 1 year, 3 years and 5 years was 37% (95% CI 19–50), 46% (95% CI 27–60) and 57% (95% CI 36–71) respectively. Six patients (15%) received vedolizumab. Four patients (10%) with VEO-IBD underwent a colectomy during the follow-up period of which two patients received vedolizumab.

Conclusion

The incidence of VEO-IBD was 2.0/100,000. Medical treatment with immunomodulators and biological therapy was used extensively, possibly reducing surgery. However, medical treatment remains a complicated balancing of the effect (anti-inflammatory), side effect (cancer risk) and surgery in VEO-IBD.
P520 ‘Eetscore’ in patients with Inflammatory Bowel Disease: an online tool to assess diet quality and provide personalised dietary advice
Authors: Lamers C R , van Erp L W , Slotegraaf A I , Groenen M J M , de Roos N M , Wahab P J , Witteman B J M
Published: May 2021

Background

Many patients with IBD believe diet affects the course of disease and is at least as important as medication in their IBD treatment. However, easy assessment of patients’ food intake and structured support of a healthy diet are lacking. The Eetscore is an online tool which assesses diet quality and subsequently gives personal dietary advice. We used the Eetscore to assess diet quality of IBD patients, evaluated if diet quality improved over time and studied correlations with quality of life (QoL) and clinical disease activity.

Methods

A prospective cohort study with adult IBD patients was performed. Participants completed the Eetscore, the short IBDQ and a clinical disease activity questionnaire (P-HBI or P-SCCAI) at baseline and after 1 month. The Eetscore is a validated web-based screening tool to assess diet quality based on 16 food components (e.g. meat, vegetables, fruit and fish). It consists of a short Food Frequency Questionnaire and is scored with the Dutch Healthy Diet 2015-index based on the Dutch dietary guidelines. The score of each component ranges from 0 to 10, resulting in a total score between 0 and 160. Higher scores indicate better adherence to Dutch dietary guidelines. The Eetscore subsequently provides personalised dietary advice based on the assessment. We assessed changes over time using paired samples t-tests or McNemar’s test and correlations using Pearson’s or Spearman’s correlation.

Results

We included 212 participants. At time of this preliminary analysis, 175 participants (60% female, 49% Crohn’s disease) completed baseline and 1-month assessments. Their median age was 49 years [IQR 32–58], BMI 25 kg/m2 [IQR 22–28] and disease duration 10 years [IQR 4–18]. At baseline, mean Eetscore was 98 ± 19, with highest median scores (≥8.5) on red meat, fat and oils, sweetened beverages, alcohol and salt intake, and lowest median scores (≤5) on nuts, legumes, processed meat and unhealthy choices (Figure 1). Diet quality increased with 5.6 points (95%CI 3.7–7.5) to a mean Eetscore of 103 ± 21 (p<0.001) after 1 month. QoL improved from 53 ± 10 to 55 ± 9 (∆2.0 (95%CI 1.2–2.8); p<0.001). The proportion of participants with clinically quiescent disease was comparable at both time points (71% vs 74%, p=0.29). Diet quality was not correlated with QoL or clinical disease activity.

Conclusion

This study suggests the Eetscore is a useful tool to monitor and support a healthy diet in IBD patients. Diet quality improved significantly following personalised dietary advice of the Eetscore. Short term results did not indicate a correlation between diet quality and QoL or clinical disease activity.
P526 Social functioning, work-productivity and psychological assessment in a cohort of patients with inflammatory bowel disease: an observational study
Authors: Todeschini A
Published: May 2021

Background

Patients with inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease, claims to suffer a significant hindrance in everyday life, because of the frequency of psychological complaints. The aim of this study was to identify and analyze social functioning, work productivity and psychological assessment in IBD patients and to correlate these parameters with history and activity of the disease.

Methods

An observational study was performed in 99 IBD patients. Psychosocial data were assessed through the administration of specific questionnaires: Social Functioning Questionnaire (QFS) for monitoring social functioning; Work Productivity and Activity Impairment questionnaire (WPAI) for work productivity; State-Trait Anxiety Inventory (STAI 1,2), for psychological assessment. IBD activity was measured by Partial Mayo score. Student’s t test or Wilcoxon rank sum test were used to compare continuous variables between subgroups and chi-square test to compare categorical variables. Univariate and multivariate linear regression were used, respectively, to assess the relationship between psychosocial and disease characteristics and to compare outcomes with determinant associated results in univariate regression.

Results

Univariate analysis showed a statistically significant correlation of the overall QFS score with both the level of education (0.6; 95% CI = 0.1–1.2; p = 0.028) and the unemployed status (- 4.5; 95% CI = -8.9- -0.1; p = 0.044). Moreover, the impairment of WPAI was greater in subjects with ulcerative colitis with severe endoscopic activity according with Partial Mayo score (15.5; 95% CI = 1.0–30.0; p = 0.038). Overall impairment in subjects with stable employment correlated with age (- 0.5; 95% CI = -0.9- -0.1; p = 0.010) and was greater in subjects who underwent at least one surgical operation (15.8; 95% CI = 3.0–28.6; p = 0.016). Psychological evaluation showed that state and trait anxiety correlated significantly with Partial Mayo score (respectively 1.8; 95% CI = 0.6–2.7; p = 0.004 and 1.3; 95% CI = 0.1–2.5; p = 0.042) and age (respectively - 0.2; 95% CI = -0.3- -0.1; p = 0.028 and - 0.3; 95% CI = -0.5 - -0.1; p = 0.037). State anxiety increased in case of long-standing illness (- 0.3; 95% CI = -0.5 - -0.1; p = 0.037), while the non-worker status correlated with trait anxiety when compared to paid employment (- 7.0; 95% CI = -0.9–13.1; p = 0.026).

Conclusion

Social functioning was correlated to the employment status and to the level of education. Work productivity was lower in UC patients with severe activity and who undergone at least one surgery related to IBD. The state of anxiety was related with age, duration and activity of illness, while the trait of anxiety was major in non-worker patients.
P556 Safety and efficacy of ustekinumab in the treatment of Crohn’s Disease: A systematic review and meta-analysis
Authors: Khorshid Fasge M , Cordie A , Abd-Elsalam S
Published: May 2021

Background

This systematic review and meta-analysis was designed to estimate the safety and effectiveness of ustekinumab in the treatment for Crohn’s disease (CD) in clinical trials and observational studies.

Methods

We retrieved all the related publications from PubMed, Cochrane, EBSCO, Google Scholar and EMBASE using a systematic search strategy. We only included the clinical trials and observational studies that were published in English.

Results

Only 31 studies that met the eligibility criteria out of the 733 identified studies were included. Twenty-one studies reported the clinical response rate; three of these were clinical trials, and the other 18 were cohort studies. The overall clinical response rate in the cohort studies was 0.539, 95% CI (0.419–0.659) with significant heterogeneity (I2 = 96.22%, P < 0.001) and that in the clinical trials was 0.428, 95% CI (0.356–0.501). The pooled clinical remission rate was 0.399, 95% CI (0.295–0.503) in randomised control trials (RCTs) and 0.440, 95% CI (0.339–0.542) in cohort studies. Twenty-one studies reported the incidence of adverse effects. The rate of adverse effects was 0.158, 95% CI (0.109–0.207) in cohort studies and 0.690, 95% CI (0.633–0.748) in RCTs. Three RCTs had an infection rate of 0.275, 95% CI (0.245–0.295), while the 18 cohort studies had a rate of 0.076, 95% CI (0.047–0.105). Only ten studies reported the incidence of injection or infusion reaction; it was 0.035, 95% CI (0.027–0.043) for RCTs and 0.012, 95% CI (0.002–0.022) for cohort studies.

Conclusion

Ustekinumab is effective in the treatment of CD. However, more research is required on the safety profiles because there was considerable variation among the included studies.
P565 Illness perception as a clinical tool to detect mood disturbances (anxiety or depression) in inflammatory bowel disease patients
Authors: De Castro Parga M L , Pereyra D , Sanromán L , Figueira M , Hernández V , Pineda J , Martinez-Cadilla J , Pereira S , Rodriguez-Prada J I
Published: May 2021

Background

In patients suffering from inflammatory bowel disease (IBD), a prevalence of anxiety and/or depression of 30–35% has been reported in phases of clinical inactivity, reaching up to 60–80% in the flare-ups. Moreover, the presence of psychological comorbidity is now considered to complicate the course of IBD. Our aim was to evaluate the relationship between mood disturbances and individual illness perception.

Methods

Patients attending our tertiary hospital IBD outpatient clinic were enrolled. They filled the “Hospital anxiety and depression scale” (HADS) and the “Brief illness perception questionnaire” (BIPQ). Sociodemographic characteristics, phenotype and clinical course of IBD were reviewed as well. Ethical approval of the study was obtained.

Results

A total of 201 patients were analyzed: male 102 (50.7%) female 99 (47.3%), UC 113 (56.2%), CD 88 (43.8%). The HADS prevalence of psychological pathology was 24%, (22% anxiety, 6.9% depression), and 17% patients previously were on mood medications. There were no differences between CU and EC, although EC patients tended to show more anxiety. Women had a higher prevalence of anxiety (29% vs 15.6%) and depression (9.6% vs 4.7%) than men (p=0.03 and p=0.009). Anxiety was also associated with previous IBD hospitalization (p=0.005), and depression with living alone (p=0.007). The BIPQ dimensions: consequences, concern and emotional response were statistically associated with the presence of psychological pathology, anxiety and depression (p=0.0005 each).

Conclusion

Mood disturbances are frequently found in IBD patients, especially among females. A negative individual illness perception of the consequences and emotions related to IBD seems to correlated strongly with the presence of anxiety and/ or depression in these patients.