bluuebunny/crossref_metadata_2025 huggingface dataset:
P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience
Authors: Calvo Moya M I , Omella Usieto I , Vera Mendoza M I , Matallana Royo V , Gonzalez Partida I , Manso Manrique M , Menchén Viso B , De Lucas Téllez de Meneses R , González Rodriguez M , Bella del Castillo P , González Lama Y
Published: January 2020

Background

Current therapeutic goals in inflammatory bowel disease (IBD) include not only the mere absence of symptoms but also the resolution of endoscopic lesions, so-called mucosal healing (MH), which has been related to better outcomes. Data regarding the achievement of MH with vedolizumab (VDZ) in real-life clinical practice is still scarce.

Methods

Retrospective cohort study was carried out in a tertiary hospital between January 2015 and April 2019 including patients with a basal colonoscopy showing activity and who achieved clinical remission under treatment with VDZ, defined by partial Mayo score <2 for ulcerative colitis (UC) and Harvey–Bradshaw Index score (HBI) <4 for Crohn’s disease (CD). Surveillance colonoscopy was performed along with the follow-up according to clinical practice. In UC patients, MH was defined as Mayo Endoscopic Subscore (MES) = 0; the endoscopic response was defined by a decrease in MES ≥1 point. In CD, MH was deﬁned by achievement SES-CD = 0–3 or Rutgeerts index i0; the endoscopic response was deﬁned by a decrease of SES-CD of 50% or Rutgeerts index <i2 with at least 1 point of decease compared with baseline.

Results

In total, 118 patients treated with VDZ were analysed, but only 45 met inclusion criteria with a median follow-up of 21 (IQR: 14–19) months. Surveillance colonoscopy was performed after a median time of 12 months (IQR:9–17) of treatment. MH achieved in 33/45 patients (73%): 17/23 CD patients (74%) and 16/22 UC patients (73%). The endoscopic response was achieved in 9 of the remaining 12 patients: 3/6 CD patients and 6/6 UC patients. Only 3 (7%) of patients included showed no endoscopic benefit at the time of surveillance endoscopy. In multivariate analysis, probability of not achieving MH was 75% in patients previously treated with immunosuppressants (ISS) (HR 0.25, 0.11–0.55 IC95; p = 0.001) and 60% in patients previously treated with anti-TNFα (HR 0.40, 0.18–0.90 95% CI; p = 0.026). Type of IBD, concomitant ISS, corticosteroid use at induction, baseline endoscopy score or duration of disease before VDZ treatment were not associated with the achievement of MH.

Conclusion

In our experience, most of the patients who achieve clinical remission with VDZ also achieve MH. Refractory patients were less likely to achieve MH despite having achieved clinical remission.
P380 What is the optimal dose of thiopurinic drugs (azatioprine) in patients with inflammatory bowel disease under treatment combined with anti-TNFα (infliximab/adalimumab)?
Authors: LUCAS RAMOS J , Suarez Ferrer C , Sanchez Azofra M , Poza Cordón J , Martín Arranz E , Martin Arranz M D
Published: January 2020

Background

The combination of anti-TNF drugs with thiopurinic (TPH) drugs in the treatment of IBD, has shown greater clinical efficacy, serum drug levels in therapeutic range in a higher proportion of patients, and less antibody formation, than monotherapy with anti-TNF. However, the dose of the TPH drug in combined treatments has not been clearly established. Some authors consider that this dose could be lower than that used in monotherapy (2.5 mg/kg/day).

Methods

A retrospective study was performed, selecting all patients with the diagnosis of IBD in follow-up at the Hospital La Paz, from 2006 to 2018, who were on combined treatment with azathioprine (AZA) and Anti-TNF. 91 patients were recruited for treatment with infliximab (IF) and 52 for treatment with adalimumab (AD). Two groups were established for both IF and AD, one with the standard dose (2–2.5 mg/kg) and one with a lower dose (less than 2 mg/kg). The main objectives are to evaluate the clinical and pharmacokinetic response: through the measurement of the levels of the biological drug and the formation of anti-drug antibodies (ADA). As secondary variables, PCR and faecal calprotectin are determined

Results

In the AD group, there are no statistically significant differences in remission rates, response without remission, or failure depending on the dose of TPH (adequate or low). There are no differences between PCR and calproctectin levels among patients with optimal doses of TPH and low doses. The last determinations of mean AD levels were not significantly different between groups. No ADA formation was detected. In the IF group, there is no statistically significant difference in remission, response or failure rates depending on the dose of TPH. There are no differences between the levels of PCR and faecal calprotectin, nor in the formation of ADA; nor in the last two determinations of mean IF levels among patients with optimal doses of thiopurines vs. lower doses. If we consider pharmacokinetic failure (infliximab levels < 1000 μg/ml and/or ADA), there were also no statistically significant differences.

Conclusion

Consistent with the findings of other studies, there are no differences in the pharmacokinetic characteristics or in the responses of patients depending on the dose of azathioprine. The use of a lower dose of AZA can provide a better tolerance of the drug, a better safety profile, and lower economic cost.
P387 Real-world clinical outcomes of biologic-naïve non-complicated Crohn’s disease patients treated with vedolizumab: Results from the EVOLVE study
Authors: Yarur A , Mantzaris G J , Kopylov U , Bassel M , Brett N , Kim H , Lopez C , Saha S , Kifnidi C , Agboton C , Adsul S , Demuth D , Luo M , Wang S , Bressler B
Published: January 2020

Background

Crohn’s disease (CD) can lead to complications that impact treatment (Tx) decisions and its clinical effectiveness. The objective of this analysis was to compare clinical effectiveness outcomes of CD patients treated with first-line biologic vedolizumab (VDZ) who did not have a complicated disease phenotype (non-complicated) to VDZ patients who had complications (complex disease).

Methods

This was a retrospective real-world cohort study of biologic-naïve CD patients (≥18 years old) in Canada, Greece and the USA who initiated VDZ Tx between May 2014 and March 2018. Data were collected from Tx initiation to the earliest of chart abstraction date or death. The non-complicated CD was defined as patients who had mild or moderate disease severity and no active fistula at Tx initiation, had no prior CD-related surgeries since diagnosis and no CD-related hospitalisations within 12 months prior to Tx initiation. The complex disease cohort encompassed all other CD patients. Cumulative rates of clinical effectiveness outcomes over 24 months (Tx persistence, clinical response and clinical remission) were estimated using the Kaplan–Meier method. Using pre-defined hierarchical algorithms, clinical response and clinical remission were assessed from standard disease measures reported in the medical records.

Results

This analysis included 218 CD patients treated with VDZ (non-complicated: 64 (29.3%); complex: 154 (70.6%) from 37 sites. Mean (SD) age at Tx initiation: non-complicated, 46.2 (15.8); complex, 54.0 (16.7); male: non-complicated, 45.3%; complex, 55.2%. Cumulative rates of clinical response were significantly greater in non-complicated than complex disease patients over 24 months (non-complicated: 93.0%, complex: 76.0%, p < 0.01) (Figure 1). Tx persistence (non-complicated: 76.7%, complex: 66.6%, p = 0.68) (Figure 2) and clinical remission (non-complicated: 81.9%, complex: 73.5%, p = 0.36) (Figure 1) were not significantly different between the two cohorts over 24 months. Fewer patients had data for mucosal healing over 24 months, and it was also not significantly different between groups at 12 months (non-complicated: 66.4%, complex: 60.2%, p = 0.95).

Conclusion

A high proportion of patients (70%) had a complex disease when VDZ Tx was initiated but those with non-complicated phenotype had a higher response rate. To help guide physicians in positioning the optimal Tx for biologic-naïve CD patients, it is important to identify the sub-group of patients who can most benefit from VDZ Tx. The results of this real-world study suggest that the biologic-naïve, non-complicated CD patients benefit more from VDZ treatment compared with those with disease complications.
P391 Side-to-side strictureplasty and its modification over the ileocecal valve for extensive Crohn’s ileitis: single-centre long-term outcome
Authors: Bislenghi G , Ferrante M , Sabino J P G , Verstockt B , Martin Perez B , Wolthuis A , Vermeire S , D’hoore A
Published: January 2020

Background

Postoperative recurrence remains a challenging problem in patients with Crohn’s disease (CD). Ileal location and extensive disease are risks factor for surgical recurrence. To avoid short-bowel syndrome, strictureplasty techniques have been proposed. Over the years, the indication for strictureplasty has further expanded to long strictures. We evaluated the long-term effect of side-to-side isoperistaltic strictureplastie (SSIS) (according to the Michelassi technique or modification of this over the ileocecal valve (mSSIS)) and its effect on bowel preservation in CD patients with extensive bowel involvement.

Methods

Fifty-two CD patients with an affected ileal segment (≥ 20 cm) were included (Figure 1). Thirty-day postoperative morbidity was assessed using the comprehensive complication index (CCI). Patients were assessed clinically at 1 and 6 months postoperatively. An ileocolonoscopy and a magnetic resonance enterography were performed 6 months after surgery. Endoscopic disease activity was assessed according to the modified Rutgeerts score (MRS). Perioperative factors related to disease recurrence were evaluated. Clinical recurrence was defined as symptomatic endoscopically (MRS ≥ i2b) or radiologically confirmed stricture/inflammatory lesion requiring initiation/escalation of the medical treatment or surgery. Surgical recurrence was defined as the need for any surgical intervention within or away from the primary strictureplasty. Endoscopic remission was defined as MRS ≤ i1. Deep remission was defined as the combination of endoscopic remission and the absence of clinical symptoms.

Results

Mean CCI for SSIS was 1.9 (Figure 2). At a median follow-up of 70.8 months (range 9.6–118.8), 19 patients (47.5%) experienced clinical recurrence. Surgical recurrence occurred in seven patients (36.9%). Four patients needed resection of the SSIS. In two patients, a Heineke–Mikulicz strictureplasty was performed at the inlet of the SSIS. The median time to clinical recurrence was 29.3 months (11.4–62.8). The median time to surgical recurrence was 42.9 months (11.9–52.7) (Figure 3). None of the perioperative variables (gender, age at surgery, Montreal classification, smoking habits, former surgery, pre- and postoperative medical therapy, length of SSIS, associated surgery, postoperative complications) correlated with clinical recurrence. At the end of the follow-up, deep remission was reached in nine patients (22.5%).

Conclusion

SSIS is safe, effective and provides durable disease control in patients with extensive CD ileitis. The majority of patients (92.3%) maintain the original SSIS after a median follow-up of 70.8 months. Although not as frequent (15%), endoscopic remission has been observed when an mSSIS has been performed.
P398 The early appearance of anti-drug antibodies during the induction phase predicts the clinical response of adalimumab and infliximab in IBD
Authors: Roblin X , williet N , veyrard P , boschetti G , berger A E , nancey S , flourie B , paul S
Published: January 2020

Background

Several studies have shown a link between circulating anti-TNF levels during induction and clinical progression during IBD. There are less data on the detection of anti-drug antibodies at induction because it requires the use of so-called ‘drug-tolerant’ techniques. The purpose of our study was to investigate in two distinct cohorts (IBD patients on IFX or ADA) whether the early appearance of anti-drug antibodies measured using a drug-tolerant test was associated with clinical progression.

Methods

In a retrospective study, we included all patients followed in our department for at least 3 months and having had an anti-TNF dosage from W2 of induction under ADA or IFX. At follow-up, therapeutic failure was defined by the obligation to optimise, a change in biotherapy, the use of corticosteroids or surgery. IFX and ADA levels were measured routinely (Lisa-Tracker; Theradiag) and anti-medicine antibodies were detected by ‘drug-sensitive’ ELISA technique (Lisa-Tracker; Theradiag) or ‘drug-tolerant’ as previously described [1]. Patients with a positive rheumatoid factor were excluded.

Results

54 patients were included in ADA (mean age: 36 years, sex ratio M/F = 54%, CD: 65%, combotherapy: 10%) and 54 treated with IFX (mean age: 35 years, sex ratio M/F: 46%, CD: 62%, combotherapy: 65%). The search for anti-drug antibodies to W2 using a ‘drug-sensitive’ technique did not reveal any antibodies, whereas 74% of patients on ADA (AAA > or = 2.5 µg/ml eq) and 55% of patients on IFX (ATI > or = 4µg/ml eq). Under ADA, the duration of treatment until loss of response was significantly shorter in the presence of AAA at W2: 6 months vs. 24 months (HR = 18.51; 95CI = 4.35–78.11; p < 0.001). In multivariate analysis, the only independent factor associated with failure was the rate of ADA antibodies to W2 (HR = 18.17; 95CI: 4.27–77.45; p < 0.001). Under IFX, the treatment time to loss of response was significantly shorter in the presence of ATI to W2 (ATI > or = 4µg/ml eq): 5.5 months vs. >24 months (HR = 13.89; 95CI = 4.08–47.31; p < 0.001). In multivariate analysis, the only independent factor associated with failure was the level of anti-IFX antibodies to W2 (> or = 4 µg/ml eq) (HR = 8.07; 95CI: 3.13–20.82; p < 0.001). The higher quartiles of ATI and AAA were significantly associated with poor outcomes (p < 0.001 for each anti-TNF).

Conclusion

The early onset of anti-drug antibodies in the induction phase as early as W2 is the only isolated independent factor associated with loss of response. Anti-drug antibody frequencies are very high when measured with a drug-tolerant test and these Abs may be more neutralising with ADA than with IFX.
P405 Comparison of long-term outcomes of infliximab vs. adalimumab in 1488 biologic-naive Korean patients with Crohn’s disease
Authors: Jung Y S , Han M , Park S , Cheon J H
Published: January 2020

Background

Data on the comparative effectiveness of infliximab (IFX) or adalimumab (ADA) in patients with Crohn’s disease (CD) are rare, particularly for Asian patients. We compared the clinically key outcomes (surgery, hospitalisation, and corticosteroid use) of these two drugs in biologic-naive Korean patients with CD.

Methods

Using National Health Insurance claims, we collected data on patients who were diagnosed with CD and exposed to IFX or ADA between 2010 and 2016.

Results

We included 1488 new users of biologics (1000 IFX users and 488 ADA users). Over a median follow-up of 2.1 years after starting biological therapy, there were no significant differences in the risk of surgery (ADA vs. IFX; adjusted hazard ratio [aHR], 1.30; 95% confidence interval [CI], 0.86–1.95), hospitalisation (aHR, 1.05; 95% CI, 0.84–1.32), and corticosteroid use (aHR, 0.84; 95% CI, 0.58–1.22) between IFX and ADA users. These results were unchanged even when only patients who used biologics for over 6 months were analysed (aHR [95% CI]; surgery: 1.41 [0.88–2.26], hospitalisation: 1.06 [0.83–1.35], and corticosteroid use: 0.82 [0.56–1.21]). Additionally, these results were stable in patients treated with biological monotherapy or combination therapy with immunomodulators.

Conclusion

In this nationwide population-based study, there was no significant difference in the long-term effectiveness of IFX and ADA in the real-world setting of biologic-naive Korean patients with CD. In the absence of trials to directly compare IFX and ADA, our study supports that the choice of one of these two biologics may be allowed to be determined by the preference of patients and/or physicians.
P411 Faecal calprotectin is more tightly associated with endoscopic disease activity compared with other biomarkers in patients with inflammatory bowel disease under maintenance treatment with adalimumab
Authors: Orfanoudaki E , Theodoraki E , Foteinogianopoulou K , Mantaka A , Koutroubakis I
Published: January 2020

Background

Fecal calprotectin (FC) has been suggested as an important biomarker for the management of patients with inflammatory bowel disease (IBD). It is an indirect index of disease activity and plays a crucial role in the treat-to-target strategy. Consecutive measurements of FC in patients in clinical remission can predict a disease relapse and lead to early treatment optimisation. We aimed to compare FC with other biomarkers as for their association with endoscopic activity in IBD patients under maintenance treatment with adalimumab.

Methods

Consecutive IBD patients under maintenance treatment with adalimumab were studied retrospectively based on prospectively recorded data in an IBD registry. Inclusion criteria were at least one available endoscopic evaluation with accompanied biomarkers measurement within the last ± 3 months in the study period (10/2016–9/2019). Biomarkers assessed were FC (home testing Βühlmann fCAL ELISA), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), haemoglobin (Hb), white blood cells (WBC) and platelets (PLT). The disease was considered as active if endoscopic Mayo score was ≥2 in ulcerative colitis (UC) and SES-CD score >6 for Crohn’s disease (CD).

Results

From a total of 72 IBD patients under maintenance treatment with adalimumab, 53 met inclusion criteria [49 CD, 32 men, mean age 42.3 ± 14.9 years, mean disease duration 13.4 ± 9.5, median adalimumab use 34 (23–65) months, combination with immunosuppressants 11 (22%)]. In the logistic regression analysis with dependent variable, the endoscopic active disease FC (mean value 470.8 ± 382.3μg/g) and ESR were independently significantly correlated with the endoscopic disease activity (OR:1.002 95% CI 1.001–1006, p = 0.003 and OR:1.05 95% CI 0.01–1010, p = 0.01 respectively). FC identified patients with endoscopic active disease with an area under the receiver operating characteristic curve (AUC) value of 0.78 (95% CI 0.64–0.88) higher than the other biomarkers [CRP, AUC 0.70 95% CI 0.56–0.82; Hb, AUC 0.55 95% CI 0.41–0.69; ESR, AUC 0.57 95% CI 0.43–0.71; PLT, AUC 0.56 95% CI 0.42–0.69 and WBC, AUC 0.43 95% CI 0.35–0.63). In the pairwise comparison of the ROC curves, there was a significant difference of the AUC of FC and the AUC of Hb, ESR, PLT and WBC (all with p < 0.05). There was no significant difference between the AUC of FC and that of CRP (p = 0.35). FC levels >413 μg/g had a sensitivity of 75% and a specificity of 76% in predicting endoscopic active disease.

Conclusion

These real-life results indicate that in IBD patients under maintenance treatment with adalimumab faecal calprotectin home testing performs better than the other biomarkers in predicting the disease endoscopic activity.
P414 Risk factors for the development of anti-drug antibodies to infliximab and adalimumab in Crohn’s disease
Authors: Khoo E , Lord A , Hanigan K , Croft A , Radford-Smith G
Published: January 2020

Background

Anti-tumor necrosis factor-α (anti-TNFa) therapy have been established as an effective maintenance treatment for complicated Crohn’s Disease (CD). However, the efficacy of Infliximab (IFX) and Adalimumab (ADM) may be affected by low serum levels and/or the presence of anti-drug antibodies (ADA). This reinforces the importance of therapeutic drug monitoring (TDM). We aim to assess the clinical benefit of proactive vs. reactive TDM. Secondly, to assess the impact of TDM on clinical management. Thirdly, to identify risk factors for low serum drug levels and the development of ADA in CD patients.

Methods

This was a single-centred observational cohort study performed at a tertiary hospital, comprising of total 229 CD patients: 142 received IFX and 87 received ADM, who have had a trough drug level, tested using enzyme-linked immunosorbent assay. Demographic and clinical data were retrospectively collected from electronic medical records. Fisher’s Exact Test was used to determine if there are nonrandom associations between variables. A p-value of less than 0.05 was considered statistically significant.

Results

One hundred and fourteen patients (49%) receiving a standard anti-TNFa regimen had subtherapeutic drug levels (67 had IFX < 3 μg/ml and 47 had ADM < 5 μg/ml). Interestingly, almost half of this cohort were asymptomatic. Reactive TDM completed among symptomatic patients have shown to have a statistically significant benefit in detecting subtherapeutic drug level (p = 0.0001). Following these results, only fifty-two patients (46%) had a change of therapy (29 IFX, 25 ADM); while the remaining sixty-two patients (54%) continued the same dosing regimen with only one documented admission within 90-days following the drug level being taken. Eight patients (4%) were found to have positive ADA, all in the presence of subtherapeutic drug levels. Two of these had a subsequent flare of their disease. They were all switched to another class of biologic therapy. Non-smoking status at diagnosis and the concomitant use of immunomodulator were found to have statistically significant associations with a therapeutic drug level (p = 0.0176 and p = 0.0001, respectively). Similarly, both of these risk factors were associated with lower risk of ADA formation (p = 0.0057 and p = 0.0165, respectively).

Conclusion

This study suggests that a large proportion of patients have subtherapeutic drug levels at standard dosing schedules. However, low drug levels do not correlate with a higher risk of complications if patients are in clinical remission. The results of this study also indicate that non-smoking status at diagnosis and the concomitant use of immunomodulator are associated with higher serum drug levels and lower risk of developing anti-drug antibodies.
P428 Oral mesalamine use in Crohn’s disease after implementation of the American College of Gastroenterology guidelines: a TARGET-IBD cohort study
Authors: Gupta N , Sands B E , Regueiro M , Dubinsky M , Rubin D , Hanson J , Aberra F , Weiss M , Watkins S , Gazis D , Long M
Published: January 2020

Background

American College of Gastroenterology (ACG) guidelines for the management of adults with Crohn’s disease (CD) in March 2018 state that oral mesalamine, ‘should not be used…to treat CD.’ 1 This abstract estimates the prevalence of any use of mesalamine among patients with CD before and after the implementation of the guideline. It also aims to describe current utilisation patterns of mesalamine in CD by disease phenotype, location, and concomitant use of biologic agents.

Methods

TARGET-IBD is a longitudinal cohort of IBD patients receiving usual care in the USA; this abstract includes CD patients enrolled between March 2017 and December 2018. Medication use was captured as any use in the follow-up period. Use of mesalamine was stratified into patients who were on mesalamine alone or patients on mesalamine and a biologic. The proportion of patients on mesalamine was estimated in time windows after the policy change to discern penetration into usual practice.

Results

732 patients from TARGET-IBD who had baseline data prior to the new recommendation were included. Of these, 14% used mesalamine only, 8% used mesalamine plus a biologic, and 78% did not use mesalamine. A total of 65% received care in academic centres and the median duration of disease at enrolment was 12 years. The distribution of patient characteristics was similar after the policy change. Six months after the ACG recommendation, 11% of patients used mesalamine only, 7% of patients were on mesalamine plus a biologic, and 82% did not use mesalamine. Prevalence of use for the 3 and 6 month time windows was similar. Subsequent therapy changes and additions in patients on mesalamine are shown in Figure 1. Location (colon vs. ileum) and type of CD (inflammatory vs. fistulising) were statistically significant predictors of the odds of any mesalamine use both before and after the policy change (OR 3.233 (CI 1.725–6.061) and 3.334 (CI 1.931–5.755, respectively)).

Conclusion

Mesalamine use remained stable in the TARGET-IBD CD population, despite the release of the ACG guideline. Individuals with colonic, inflammatory disease were more likely to receive mesalamine, as were Medicare recipients. There was little difference between academic and community practice in implementation of the new standards. Given that the guidelines are relatively new, it is important to follow these participants over a longer period and monitor practice differences and ways to reinforce the practice recommendations to improve the quality and cost of care.
P431 Vitamin D binding protein in the limelight: IBD-related inflammation and circulating levels of vitamin D binding protein, total, free and bioavailable 25-hydroxyvitamin D
Authors: Aksan A , Böttger K , Hein N , Caicedo-Zea Y , Diehl I , Schumann C , Armbruster F P , Stein J M
Published: January 2020

Background

Vitamin D deficiency occurs frequently in patients with Crohn’s disease (CD) and ulcerative colitis (UC). While recent cohort studies support an association of vitamin D with important clinical parameters and outcomes in IBD, the complex interplay of inflammation with vitamin D metabolism in IBD poses a viscious circle. We sought to further illucidate the relation between inflammation and different vitamin D parameters. To the best our knowledge, this was the first study to focus on the relationship between vitamin D binding protein (VDBP), circulating total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D), and inflammation, in adult IBD patients.

Methods

This was a comparative, single-centred, cross-sectional study in patients with IBD aged 18–65 years. Full blood count, transferrin, albumin and hsCRP were determined by standard methods. The presence/absence of inflammation was assessed based on serum hsCRP levels (cutoff <5mg/l). VDBP levels were determined by ELISA, and 25(OH)D by LCMS. Free and bioavailable vitamin D levels were calculated using the validated formula. IBM SPSS version 25.0 was used for statistical analysis.

Results

In total, 129 subjects with IBD (70 male/59 female; 82 CD/47 UC; mean age 41.7 ± 12.6 years) were enrolled. Of these, 38/129 had inflammation (19 m/19 f; 26 CD/12 UC; 39.6 ± 12.9 years) while 91/129 had no inflammation (40 m/51 f; 56 CD/35 UC; 42.5 ± 12.5 years). Subjects with disease activity had significantly higher leukocyte, erythrocyte sedimentation rate (ESR) and hsCRP, but lower transferrin, transferrin saturation (TSAT) and albumin levels than those without inflammation (p < 0.05). Average serum levels of 25(OH)D (24.6[6.8–54.8] vs. 26.4[5.0–74.4]ng/ml), free 25(OH)D (5.9[1.3–13.3] vs. 1.0[1.0–21.4]ng/ml) and bioavailable 25(OH)D(2.3 [0.1–4.7] vs. 2.4[0.5–19.5]ng/ml) were similar in patients with vs. without inflammation (p > 0.05). However, VDBP levels were significantly higher in inflammatory conditions (359.6[252.2–530.6] mg/l vs. 327.4[183.5–560.3]mg/l; p < 0.05) and showed a positive correlation with CRP levels (0.293, p < 0.001). Ratio of free/total 25(OH)D correlated negatively with CRP levels (−0.282, p = 0.002).

Conclusion

High levels of circulating VDBP were associated with inflammatory activity. Moreover, free/total 25(OH)D ratio was inversely associated with inflammation. Other vitamin D parameters including total, free and bioavailable 25(OH)D showed no association with inflammation. These findings suggest that VDBP may play a bigger role than thought as a modulator of vitamin D and inflammation, and that simultaneous detection and investigation of plasma VDBP may provide additional insights into this complex interaction.
P434 Effectiveness and safety of ustekinumab in ulcerative colitis: real-world evidence from Eneida Registry
Authors: Chaparro M , Garre A , Iborra M , Barreiro-de Acosta M , Casanova M J , De Castro L , Fernández-Clotet A , Hinojosa J , Boscá-Watts M , Busquets D , López-García A , Lorente R , Manceñido N , Martínez T , Monfort D , Pérez-Calle J L , Villoria A , Angueira T , Bermejo F , Carbajo A Y , Carpio D , González-Muñoza C , Gomollón F , Huguet J M , Rivero M , Iglesias-Flores E , Sierra M , Hernández-Villalba L , Domènech E , Gisbert J P
Published: January 2020

Background

Ustekinumab has shown promising results in ulcerative colitis (UC) in the development program (UNIFI) that should be confirmed in clinical practice. Our aim was to evaluate the effectiveness and safety of ustekinumab in UC in real life.

Methods

Patients included in the prospectively maintained ENEIDA registry that received at least 1 dose of ustekinumab intravenously due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score (PMS). The short-term response was assessed at week 8 and 16. The last-observation-carried-forward method was used in patients that stopped ustekinumab treatment before week 8 or 16. Variables associated with short-term remission were identified by logistic regression analysis. Data quality was assessed by remote monitoring.

Results

Forty-seven patients were included (Table 1); all of them had been previously exposed to biologic agents (70% to >2): 100% to anti-TNF and 83% to vedolizumab. A total of 26% had been exposed to tofacitinib. Seventeen patients (36%) had response at week 8 [3 of them (6%) had remission]; 16 patients (34%) had response at week 16 [5 of them (11%) had remission] (Figure 1). There was a statistically significant decrease in C-reactive protein (CRP) concentration during the induction only in patients with a response at week 16 (Figure 2). The proportion of patients with CRP elevated at baseline and at week 8 was higher among non-responders at week 16 (Table 2). In the multivariate analysis, higher PMS at week 8 [odds ratio (OR) = 0.5; 95% confidence interval (CI) = 0.3–0.9)] and CRP over the upper normal limit at week 8 (OR = 0.1; 95% CI = 0.01–0.8) were associated with lower probability of response at week 16; steroids during induction increased the probability of response at week 16 (OR = 8; 95% CI = 1–71). Of patients without response at week 8, only 7% achieved response at week 16. Seventeen out of 31 patients continued ustekinumab beyond week 16, despite being non-responders. Of these 17 patients, 4 reached remission after the third dose, 1 after the fifth and 1 after the seventh one. There were 2 infections, one of them with fatal consequences (in a patient under steroids and tacrolimus due to renal transplant).

Conclusion

Ustekinumab shows benefit in some UC patients in real practice, even in a very refractory cohort in which the drug was prescribed as last resort. Patient status at week 8 seems to be a good predictor of response after the induction. Safety was consistent with the known profile of ustekinumab.
P445 Efficacy and safety of induction therapy with calcineurin inhibitors followed by maintenance therapy with vedolizumab in severe ulcerative colitis: a large patient cohort with long-term follow-up
Authors: OLLECH J , Dwadasi S , Normatov I , Israel A , Rai V , Sossenheimer P , Christensen B , Dalal S , Pekow J , Sakuraba A , Cohen R , Rubin D
Published: January 2020

Background

The options for the medical management of patients with severe ulcerative colitis failing IV steroids are limited and include the calcineurin inhibitors cyclosporin or tacrolimus, especially in patients who had previously failed anti-TNF agents. Following induction therapy with a calcineurin inhibitor, transitioning to vedolizumab as maintenance therapy could be an option. We report on the largest cohort of patients successfully induced with calcineurin inhibitors who were then transitioned to vedolizumab maintenance therapy.

Methods

We performed a retrospective observational study of adult ulcerative colitis patients followed at the University of Chicago Inflammatory Bowel Disease Center. Patients with severe steroid-refractory ulcerative colitis were included if they received a calcineurin inhibitor (ciclosporin or tacrolimus) as induction therapy followed by maintenance therapy with vedolizumab between January 2014 and December 2018. Patients who had a follow-up of fewer than three months were excluded. The primary endpoint was colectomy-free survival. Secondary endpoints included survival without vedolizumab discontinuation as well as clinical, steroid-free and biochemical remission at week 14.

Results

A total of 71 patients (59% male) were treated with vedolizumab after induction therapy with calcineurin inhibitors for severe steroid-refractory colitis. Truelove and Witts criteria for Acute Severe Ulcerative Colitis were fulfilled in 77% of patients, and 97% of patients had moderate to severe endoscopic disease. Patients were followed for a median time of 25 months (IQR 16–36). Colectomy free survival rates from vedolizumab initiation were 67% at one year and 55% at two years (Figure 1, Panel A). At the end of induction with vedolizumab at week 14, 50% of patients were in clinical remission, and 62% of patients had a normal CRP. At one and two years following vedolizumab initiation, 43% and 28% of patients were still on vedolizumab, respectively (Figure 1, Panel B). Vedolizumab was dose escalated to infusions every four weeks in 44% of patients. The median time to dose escalation was 5.6 months (IQR 4.1–8.2). No serious adverse events were recorded in our patient cohort.

Conclusion

Transitioning to vedolizumab following induction of remission with calcineurin inhibitors is effective and safe. Such a treatment strategy should be considered in patients with severe steroid-refractory ulcerative colitis, especially in cases of previous anti-TNF failure.
P449 Systematic review with meta-analysis: risk of lymphoma associated with anti-tumour necrosis factor (TNF) agents in inflammatory bowel disease
Authors: CHUPIN A , Perduca V , Bellanger C , Carbonnel F , Dong C
Published: January 2020

Background

We performed a systematic review and meta-analysis to investigate the risk of lymphoma in patients with IBD treated with anti-TNF agents and thiopurines, alone or combined.

Methods

We conducted a systematic review of studies including IBD patients treated with anti-TNF and/or thiopurines from Pubmed, Embase and Cochrane databases until May 1, 2019. Two methodology reviewers (AC, CD) separately and repeatedly screened and selected studies according to study selection criteria, collected data and assessed quality. The meta-analysis used the mixed-effect Poisson models (particularly generalised linear mixed models, GLMM) to estimate incidence rate ratios (IRRs) in patients unexposed and exposed to anti-TNF, thiopurines and combotherapy (anti-TNF and thiopurines).

Results

We identified 4 998 citations. Fourteen studies were eligible for the meta-analysis. There were 8 observational studies involving 265 171 patients and 6 randomised controlled trials involving 2 311 patients (table). As compared with unexposed patients, those exposed to anti-TNF, thiopurines and combotherapy had IRRs (per 1000 patient-years) of 1.66 ([CI 95%, 1.18–2.35], p = 0.004 with I2 = 0%), 3.32 ([CI 95%, 1.87–5.90], p < 0.001 with I2 = 66.83%) and 2.64 ([CI 95%, 1.17–5.93], p = 0.02 with I2 = 1.69%), respectively. The risks of lymphoma did not differ between anti-TNF and thiopurines, between combotherapy and anti-TNF and between combotherapy and thiopurines (table). The results were unchanged when the meta-analysis was restricted to observational studies.

Conclusion

These results show that the risk of lymphoma is higher in IBD patients treated with anti-TNF monotherapy and combination therapy compared with patients unexposed to anti-TNF or thiopurines.
P473 Long-term follow-up of switching from original adalimumab to adalimumab biosimilar: real-world data in IBD
Authors: Padilla Suarez C , Webb K , Persad N , Sercombe J , Tyler E , Klimova K
Published: January 2020

Background

Studies have reported good efficacy outcomes for patients with inflammatory bowel disease (IBD) treated with biosimilars. There are limited long-term data. We assessed the long-term efficacy data and safety after switching from adalimumab to adalimumab biosimilars in patients with IBD.

Methods

A prospective single-centre observational study involving patients with Crohn’s disease or ulcerative colitis switched from adalimumab to adalimumab biosimilar and reviewed up to 12months. Efficacy and loss of response were measured using the Harvey–Bradshaw (HB) index and partial Mayo score for patients with Crohn’s disease and ulcerative colitis respectively. Blood tests including C-reactive protein, adalimumab drug levels and anti-drug antibodies were monitored. We have recorded side effects and possible serious adverse effects. The plan is to continue the study for 24 months.

Results

109 patients with IBD have completed at least 6 months of treatment with adalimumab biosimilar, 12 of which have ulcerative colitis and 97 Crohn’s disease. Most of them (88%) continued on biosimilar after 6 months. Patients discontinued the therapy due to loss of response or development of antibodies in one case. Two patients were switched to a different biosimilar due to the presence of side effects which were however not serious. Of those who remained on the treatment, 74.5% were in clinical remission at 6 months and 71.4% at 9 months. HB index, partial Mayo score, C-reactive protein and adalimumab drug levels did not show significant changes. We have not reported any serious adverse events. We hope than by February, at least 60% of these patients will have been on Adalimumab for 12 months and further amended date would be added.

Conclusion

Most of the patients switching from original adalimumab were maintained on biosimilar at 6 and 12months of follow-up with similar efficacy and safety as the original drug.
P477 Italian real-life study evaluating the long-term effectiveness of vedolizumab for the treatment of inflammatory bowel disease: the elderly cohort
Authors: Pugliese D , Privitera G , Armuzzi A
Published: January 2020

Background

Vedolizumab (VDZ) is the first biological therapy for Inflammatory Bowel Disease (IBD) tested, in pivotal trials, on patients up to 80 years old and has usually been presented as a safer choice in frail patients. However, real-world data on the effectiveness and safety of VDZ in elderly (≥ 65 years) are scarce. The aim of this study is to explore the effectiveness and safety of VDZ in a large real-life cohort of elderly IBD patients, with a 2 years follow-up.

Methods

The Long-term Italian Vedolizumab Effectiveness (LIVE) study included CD and UC patients started on VDZ from April 2016 to June 2017 at 40 centres of the Italian Group for the study of inflammatory bowel disease (IG-IBD). Patients were prospectively followed-up to June 2019. Co-primary endpoints were to evaluate cumulative VDZ treatment persistence and safety.

Results

Of 966 patients, 174 (18%; 81 CD, 93 UC) were ≥ 65 years old at enrolment. Mean disease duration at baseline was 10.9 years ± SD10 (CD 12.5 ± 11, UC 9.6 ± 9). VDZ was used as a first biologic therapy in 78 patients (44.8%). 25 patients (14.4%) had a history of previous cancer. The majority of CD patients had a stricturing behaviour (45, 55.6%) and had already undergone surgery (41, 49.4%). 48 UC patients (51.6%) had extensive colitis. Moderate-to-severe endoscopic activity was present in 80% of CD and in 92% of UC, according to SES-CD and endoscopic Mayo score, respectively. Cumulative VDZ treatment persistence at 12 and 24 months was 71.8% (71.6% CD and 72.0% UC) and 54% (54.2% CD and 53.8%% UC), respectively. 52.9% (40 CD; 52 UC), 4.0%, 3.5%% and 2.9% of patients were on concomitant steroids at baseline, 6, 12, and 24 months, respectively. Clinical remission at 12 and 24 months was achieved in 28.7% (31 CD and 29 UC) and in 31.6% (25 CD and 30 UC) of patients. Mean C-reactive protein was 15.6 mg/l ± SD 20 (CD 15.9 ± 21; UC 15.2 ± 19) at baseline and dropped to 8.4 mg/l ± 10 (CD 8.0 ± 8, UC 8.9 ± 11) at 12 months and to 5.9 mg/l ± 6 (CD 5.8 ± 5, UC 6 ± 7) at 24 months. Dose escalation was necessary for 20.3% and 24.7% of patients within the first 12 and 24 months. 44 adverse events were reported: 16 infections.,6 new diagnosis of cancer/dysplasia (2 colon, 1 kidney, 1 prostate, 1 lung, 1 melanoma), 4 arthritis, 3 skin rash, 2 drug-induced cholestasis,11 miscellaneous. 11 patients (6.3%) underwent VDZ withdrawal because of adverse events (6 new diagnosis of cancer/dysplasia; 4 infections; 1 cholestasis). One patient died for pneumonia complications.

Conclusion

In this preliminary analysis of the largest reported real-world cohorts of elderly IBD patients treated with VDZ, up to 55% of patients persisted on therapy after two years; an acceptable safety profile was observed throughout the entire follow-up period.
P479 The effect of adalimumab on linear growth in children with Crohn’s disease: a post hoc analysis of the PAILOT randomised control trial
Authors: Matar M , Shamir R , Turner D , Broide E , Weiss B , Ledder O , Guz-Mark A , Rinawi F , Cohen S , Topf-Olivestone C , Shaoul R , Yerushalmi B , Ben-Horin S , Assa A
Published: January 2020

Background

Growth impairment is common in children with Crohn’s disease. We aimed to assess the effect of adalimumab treatment on linear growth in children with Crohn’s disease in a post-hoc analysis of the PAILOT randomised controlled trial.

Methods

Children 6–17 years old with moderate-to-severe Crohn’s disease, naïve to biologic treatment, who responded to adalimumab induction, were assessed at week 4, 8 andevery8 weeks thereafter until week 72 for anthropometric parameters (height, weight and body mass index, BMI, Z-scores). We also analysed the associations of these parameters with clinical disease activity, inflammatory biomarkers, faecal calprotectin and adalimumab trough concentration.

Results

Overall, 66 patients had available anthropometric parameters between week 4 to 72(29% females, mean age 14.3 ± 2.6 years). The median improvement of height z–score /month was +0.014, 95% CI 0.004–0.024, p = 0.006 with an overall improvement during the study period from -0.62 (IQR −1.6–0.15) to −0.33 (IQR -1.3–0.5). The median increase of weight z- score/month was +0.025, 95% CI 0.015–0.034, p = 0.025 [overall increase from -0.54 (IQR −1.2–0.15) to −0.1, (IQR -0.9–0.6)], whereas the median increase in BMI z –score/month was +0.02, 95% CI 0.008–0.031, p = 0.001 [overall increase from −0.4 (IQR −1.0–0.5) to 0.0 (IQR −0.8–0.9)]. There was a significant correlation between paediatric Crohn’s disease activity index and erythrocyte sedimentation rate at week 4 and height z-score changes (p = 0.043 and p = 0.048), respectively, and a marginal correlation with C-reactive protein (p = 0.06). There was a significant correlation between sustained clinical and biologic remission (weeks 4–72) and changes in height z-score during follow-up (p = 0.001). Faecal calprotectin, adalimumab trough concentrations and combination therapy with an immunomodulator were not associated with height z-score changes.

Conclusion

Adalimumab treatment significantly improved linear growth, and normalised weight and BMI in children with moderate-to-severe Crohn’s disease.
P481 Repeated surgery for recurrent ileocolonic Crohn’s disease: does the outcome keep worsening operation after operation? A comparative study of 1224 consecutive procedures
Authors: Colombo F , Frontali A , Baldi C , Lamperti G M B , Maconi G , Ardizzone S , Foschi D , Sampietro G
Published: January 2020

Background

Despite relevant improvement in the medical treatment of ileocolic Crohn’s disease (CD), still surgery is needed in 80% of patients and clinical recurrence occurs in more than 50% of cases after surgery. Aim of the study is to assess the outcome for patients undergoing repeated surgery for recurrent CD.

Methods

All patients undergoing surgery for ileal or colonic CD between 1993 and 2018 in our tertiary care centre were retrospectively reviewed. We considered all small bowel resections, colonic resections, conventional (SP) and not conventional strictureplasties (NCSP).

Results

In the study period, 1224 CD patients underwent a surgical operation. We performed 713 (58.2%) primary operations (1R), 325 (26.5%) re-operations (2R group) and 186 (15.3%) three or more interventions (≥3R group). A CD diagnosis and the time of first surgery at early age were a negative prognostic factor, favouring repeated surgery in the time (R1 vs. R2p < 0.004 and R1 vs. ≥3R p < 0.0001 comparing age at diagnosis; R1 vs. R2p < 0.0001 and R1vs. ≥3R< 0.0001 regarding the time to firstt surgery). The indication for surgery (stenosis, fistula/abscess and refractoriness to medical therapy) does no’t change significantly with the number of surgeries regarding the analysis of variance of the three groups (p = 0.3). In the repeated surgery (R2 and ≥3R group) the incidence of recurrence appears to be more frequent at the anastomotic site for the 2R group (197/325, 61% vs. 103/186, 55% p < 0.05) and at SP site for the ≥3R group (19/325, 5% vs. 23/186, 12% p < 0.01). The ≥3R group underwent to a higher number of strictureplasties in comparison to the 1R group (100/186, 53% vs. 305/713, 43% p < 0.0001) and the 2R group (100/186, 53 vs. 127/325, 43% p < 0.0004). The duration of the surgical procedure tends to be higher for the ≥3R group but without reaching a statistical significance (p = 0.2). Postoperative morbidity (Clavien Dindo I-V) was increased in the 2R and in the ≥3R group but not in a significant way: (1R group n = 187 (26%); 2R group n = 102 (31%); ≥3R group n = 64 (34%); 1R vs. 2R p = 0.1, 2R vs. ≥3R group p = 0.5). In particular there was no difference between the groups in the incidence of severe postoperative morbidity (Clavien-Dindo ≥3): 1R group n = 69 (9.6%); 2R group n = 37 (11%); ≥3R group n = 24 (12%); 1R vs. 2R p = 0.4, 2R vs. ≥3R group p = 0.7.

Conclusion

In this series, we treated more than 40% of the small bowel segments with SP and NCSP at first surgery. This percentage gradually increases to 49% in 2R group and to 53% in ≥3R group. Even if the overall morbidity rate was higher, repeated surgery for recurrent CD doesn’t appear to be related to an increased risk of severe postoperative morbidity in our experience.