bluuebunny/crossref_metadata_2025 huggingface dataset:
P450 Thioguanine and low dose thiopurines and allopurinol are both safe options after failure of conventional thiopurines: a comparative analysis of two multicentre cohorts
Authors: Biemans Drs V , Savelkoul E , Dijkstra G , Simsek M , Gabriels R , Pierik M , West R , de Boer N , Hoentjen F
Published: January 2020

Background

Both thioguanine (TG) and low dose thiopurines and allopurinol (LDTA) can be considered for the treatment of inflammatory bowel disease (IBD) when conventional thiopurines fail due to intolerance or adverse events (AE). However, head-to-head trials are currently not available. The aim of this study was to compare the safety of TG and LDTA in IBD patients.

Methods

Adult IBD patients who failed conventional thiopurines and initiated LDTA in standard care were identified in the observational prospective multicentre ICC Registry. IBD patients who failed conventional thiopurines and initiated TG were retrospectively enrolled in three university hospitals. Patients with concomitant treatment with biologicals were excluded. The primary outcome was discontinuation of therapy due to AE. Secondary outcomes included: medication-related AE, infections (moderate: oral medication, severe: intravenously administrated medication), hospitalisations, and biological- and corticosteroid-free clinical remission (i.e. physician global assessment = 0) after 104 weeks of treatment. To adjust for confounding and selection bias, both multiple logistic regression and propensity score matching (PSM) were used to correct for baseline characteristics associated with disease severity or therapy refractoriness.

Results

In total, 182 IBD patients treated with TG (n = 94) or LDTA (n = 88) were included with a median follow-up of 104 weeks (IQR 91–104). The median dose of TG was 0.27 mg/kg (IQR 0.22–0.32), for LDTA: 100 mg allopurinol with either 0.67 mg/kg (IQR 0.54–0.75) azathioprine (n = 45) or 0.35 mg/kg (IQR 0.28–0.38) mercaptopurine (n = 41) (n = 2 unknown). By PSM, 64 TG patients were strictly matched with 64 LDTA patients with comparable baseline characteristics. In total, 19% (TG: 20%, LDTA: 18%) of patients discontinued therapy due AE. After adjusting for confounders, there were no significant differences in terms of discontinuation rate due to AE (TG: n = 19, LDTA = 16, OR 0.50 95% CI 0.15–1.68 p = 0.26), other AE (TG: n = 46, LDTA: n = 44, OR 0.89 95% CI 0.44–1.81 p = 0.75) (no cases of nodular regenerative hyperplasia of the liver were reported), infections (TG: n = 13, LDTA: n = 18, OR 1.05 95% CI 0.40–2.73 p = 0.93), hospitalisations (TG: n = 5, LDTA: n = 9, OR 2.00, 95% CI 0.64–6.23 p = 0.23), or biological- and corticosteroid-free clinical remission (OR 0.74 95% CI 0.33–1.68 p = 0.48). Escalation to biological treatment was comparable (TG 21% vs. LDTA 24% p = 0.68). All these results were in line with the PSM cohort.

Conclusion

A relative low percentage of patients with prior failure to conventional thiopurines discontinued therapy with TG or LDTA due to AE. Both maintenance therapies may be considered after failure of conventional thiopurines before escalating to biological therapy.
P467 Can induction and maintenance serum vedolizumab levels predict long-term clinical outcome in inflammatory bowel disease (IBD)?
Authors: Miller C , Morgan H , Steel A , Wahed M
Published: January 2020

Background

Vedolizumab (VDZ) is an established IBD therapy, however, the role of therapeutic drug levels (TDM) is not fully established.1 Our aim was to assess whether week 6 and maintenance serum trough VDZ levels predict the clinical outcome at week 52.

Methods

A retrospective review of patients with Crohn’s disease (CD) or ulcerative colitis (UC) on VDZ was performed. Twenty-one IBD patients with serum VDZ trough level monitoring between January 2016 and December 2017 were identified. All patients received VDZ induction and maintenance as per standard protocol. Patients were excluded if complete dataset of VDZ levels was not available. Clinical remission was defined as a partial Mayo score < 2 for patients with UC or a Harvey–Bradshaw index (HBI) score < 4 for those with CD. A trough VDZ level ≥ 27 μg/ml cut-off was used to evaluate remission outcomes for both induction and average maintenance VDZ levels. Statistically, analysis was carried out using the Fisher exact test. Key demographics are 57% CD, 43% UC; Baseline HBI score: 11; Baseline Partial Mayo score: 9; Concurrent Immunomodulator: 55%

Results: (

1) Week 6 induction levels: At week 52, 69% of patients were in clinical remission. Those patients in remission had a higher mean and median trough VDZ levels (Figure A). When the induction serum trough VDZ level ≥ 27 μg/ml 30% more patients were in clinical remission at week 52, although this failed to reach statistical significance (p = 0.40) (Figure C). (2) Average maintenance VDZ levels: At week 52, 63% of patients were in clinical remission. Those patients in remission had a higher mean and median average maintenance trough VDZ levels (Figure B). When the average maintenance trough VDZ level was ≥ 27 μg/ml 17% more patients were in clinical remission, this failed to reach statistical significance (p = .0.39) (Figure D).

Conclusion

High levels of clinical remission in both CD and UC were seen. In our study, we could use a similar cut-off for induction trough VDZ levels to those used in the literature that correlated with positive outcomes.1 Although the observed levels used to predict remission did not reach statistical significance, this may represent a type 2 error in view of the small numbers of patient. Furthermore, it was not possible to assess whether there is a difference between CD and UC. For maintenance levels, our cut-off of 27 μg/ml was higher than that used in the literature that correlated with positive outcomes.1 Our data suggest there is some correlation between trough VDZ levels for both induction and average maintenance levels and long-term clinical remission. Our induction cut-off was similar to currently available data associated with positive outcomes.1 Further studies are required to fully establish the role of TDM.

References
P476 Efficacy and safety of 2 vedolizumab IV regimens in patients with perianal fistulising Crohn’s disease: results of the ENTERPRISE study
Authors: Schwartz D , Peyrin-Biroulet L , Lasch K , Adsul S , Danese S
Published: January 2020

Background

Perianal fistulae occurring with Crohn’s disease (CD) are a challenge to treat. Vedolizumab (VDZ) is a gut-selective, monoclonal α 4β7 integrin antibody approved to treat patients (patients) with moderately to severely active CD. Here we report results from ENTERPRISE (NCT02630966; EudraCT 2015-000852-12), a randomised, double-blind, phase 4 trial to evaluate 2 VDZ IV dosing regimens in patients with fistulising CD.

Methods

Patients with moderately to severely active CD and 1–3 draining perianal fistulae received either VDZ 300 mg IV at Weeks (Week) 0, 2, 6, 14, and 22 (VDZ), or the same regimen plus an additional VDZ dose at Wk10 (VDZ+Wk10). The primary endpoint was the proportion of patients with a ≥50% reduction from baseline (BL) in the number of draining fistulae (absence of draining despite gentle finger compression) at Wk30. Secondary endpoints were the proportion of patients with a ≥50% reduction from BL in the number of draining fistulae at Wk22 and Wk30, and the proportion of patients with 100% fistulae closure at Wk30. Patients with missing data at study visits were counted as non-responders. Perianal disease activity index (PDAI), perianal pain score, Van Assche score, gadolinium contrast enhancement by pelvic MRI, and safety were assessed. Study enrolment closed early due to slow recruitment; thus, all analyses are descriptive.

Results

Of the 32 patients with post-BL assessment of fistulae healing (full analysis set, FAS), 28 had ≥1 draining fistula at BL (modified FAS). Median CD duration was 8.5 years (VDZ [n = 14]: 11.2 years; VDZ+ Week 10 [n = 14]: 6.1 years). In each arm, 11 patients (78.6%) had prior anti-tumour necrosis factor therapy at BL; concomitant corticosteroid use was 21.4% (VDZ) and 14.3% (VDZ+ Week 10), and concomitant immunosuppressant use was 28.6% (VDZ) and 21.4% (VDZ+ Week 10). At Wk30, 53.6% of all patients achieved ≥50% decrease in the number of draining fistulae (VDZ: 64.3%; VDZ+ Week 10: 42.9%; Figure 1). The proportion of patients with fistulae response increased rapidly and remained high through Week 30 (Figure 2); 46.4% of patients (VDZ: 57.1%; VDZ+Week 10: 35.7%) achieved ≥50% decrease in the number of draining fistulae at both Weeks 22 and 30. Closure of all fistulae draining at BL was observed at Week 30 in 42.9% of patients (VDZ: 50.0%; VDZ+ Week 10: 35.7%). In the FAS, mean (SD) PDAI scores changed from BL to Weeks 30–4.1 (3.3) and perianal pain scores changed –2.2 (2.7) (table). At Wk30, mean (SD) Van Assche scores and contrast enhancement scores changed –1.1 (3.1) and –9.5 (69.4) from screening, respectively. No new safety signals were observed.

Conclusion

Over half of CD patients treated with VDZ had reductions of ≥50% in the number of draining perianal fistulae. Clinically relevant reductions in draining fistulae were seen as early as Wk2 and maintained through Wk30.
P485 Switching infliximab biosimilar: No adverse impact on inflammatory bowel disease control or drug levels with the first or second switch
Authors: Luber R , O’Neill R , Singh S , Arkir Z , Irving P
Published: January 2020

Background

Biological medicines account for a significant cost to healthcare systems. With the advent of anti-tumour necrosis factor biosimilars, switching from originator to biosimilar has enabled cost saving in inflammatory bowel disease (IBD) without compromising disease control. However, with more biosimilars entering the market, the effect on IBD activity and pharmacokinetics (PK) of a second switch to another biosimilar is uncertain. This study aims to assess the effect on disease activity and drug levels associated with switching from infliximab (IFX) biosimilar Remsima® (Celltrion, Hungary) to another biosimilar, Flixabi® (Samsung Bioepis, The Netherlands), and to compare those switching for the first and second time.

Methods

All IBD patients on IFX biosimilar Remsima® were prospectively followed during their switch to Flixabi® in a single centre. Baseline data including C-reactive protein (CRP), trough IFX level, and clinical disease activity indices were collected; Harvey Bradshaw Index for Crohn’s disease (CD) and Simple Clinical Colitis Activity Index for ulcerative colitis (UC). These indices were repeated after at least two infusions of Flixabi®.

Results

221 patients (179 CD, 42 UC) on stable IFX treatment were included in the study. 174 (79%) were on a concomitant immunomodulator. 5 (2%) patients ceased IFX prior to follow-up due to sustained remission, and 3 (1%) patients discontinued due to factors not directly related to drug or disease. 112 patients had PK analysis performed pre and post switch. An increase in IFX trough level was observed after switching IFX biosimilars; baseline median (IQR) trough level of 4.5µg/ml (2.9–6.3) compared with post switch of 5.1µg/ml (3.4–7.0) (p = 0.02). There was no difference in clinical scores or CRP post switch, and no new anti-IFX antibodies were detected. 107 patients (48%) were switching IFX agent for the second time, of which 51 had PK analysis performed. A similar increase in median IFX trough level was observed post switch in those switching for the first (4.7 vs. 6.1 µg/ml, p = 0.03) and second (4.0 vs. 4.5µg/ml, p = 0.05) times (Figure 1). No change in clinical disease activity or CRP occurred in either group. Concomitant immunomodulator and disease classification had no impact on change in IFX level (p = 0.72 and 0.37, respectively, on univariate analysis).

Conclusion

In a cohort of IBD patients switching to a new IFX biosimilar either for the first or second time, an increase in IFX level was observed with no impact on clinical and biochemical disease activity indices. Switching IFX biosimilars in IBD appears safe in the short term with respect to maintaining drug pharmacokinetic profile and disease control whether switching for the first or second time.
P490 Assessment of body weight changes in patients with inflammatory bowel diseases initiating biologic therapy: A prospective cohort study
Authors: Borren N , Tan W , Jess A , Li P H M , Garber J , Luther J , Colizzo F , Khalili H , Ananthakrishnan A
Published: January 2020

Background

Biologic therapies are effective in inducing sustained clinical and endoscopic remission in inflammatory bowel diseases. While side effects are infrequent, prior studies have inconsistently suggested that tumour necrosis factor α (anti-TNF) therapy may be associated with weight gain. We performed this prospective study to compare weight gain across different biologic therapy classes with distinct mechanisms of action.

Methods

This prospective cohort study recruited patients with moderate to severe IBD initiating outpatient biologic therapy with anti-TNF (infliximab, adalimumab), vedolizumab or ustekinumab. Weight measurements were performed at weeks 0, 14, 30 and 54. Disease activity at these time points was assessed using the Harvey Bradshaw Index (HBI) for CD and Simple Clinical Colitis Activity Index (SCCAI) for UC. Remission was defined as HBI <4 or SCCAI 2. Changes in weight between baseline and each of the follow-up visits were modelled as a continuous variable and multivariate regression assessed the independent effect of therapeutic class on this outcome.

Results

Our study enrolled 314 patients (197 CD, 117 UC) initiating biologic therapy with 120 patients starting anti-TNF (38%), 140 patients started vedolizumab (45%) and 54 patients on ustekinumab (17%). All patients provided their weight and height at baseline; 261, 184 and 131 patients provided data on weight at week 14, week 30 and week 54, respectively. The mean baseline body weight was similar among all therapeutic classes. Patients initiating UST were more likely to have Crohn’s disease (CD), have perianal involvement and have prior biologic exposure. From baseline, the weight significantly increased at week 14 with a mean of 0.36 kg ( ± 3.8kg, p = 0.004) and continued to increase compared with baseline with 0.96 kg ( ± 3.9kg, p < 0.001) and 1.29 kg ( ± 4.2kg, p < 0.001) at week 30 and 54, respectively (Figure 1). On univariate and multivariable analysis, no significant differences between any of the biologic therapies for weight gain was seen at any time point (weight gain anti-TNF: 0.31 kg, 1.06 kg, 1.33 kg; VDZ: 0.30 kg, 0.83 kg, 1.10 kg; UST: 0.63 kg, 1.21 kg, 2.31 kg at week 14, week 30, week 54, respectively) (Figure 2). Weight gain at week 14 was significantly higher in those with CD (+1.25 kg, 95% CI 0.19–2.30, p = 0.021) and being on steroids at baseline (+1.07kg, 95% CI 0.03–2.10, p = 0.043). Early weight gain predicted continued weight gain at week 30 (+0.83kg, 95% CI 0.63–1.03, p < 0.001) and week 54 (+0.48, 95% CI 0.21–0.74, p = 0.001). Neither clinical response to therapy nor disease activity parameters showed any statistical association with weight gain.

Conclusion

There was no difference in weight gain between the different biologic therapeutic classes.
P505 Different failure rates after non-medical switching of 744 patients from adalimumab originator to 2 different adalimumab biosimilars at Cambridge University Hospitals, UK: real-world experience
Authors: Rosembert D , Malaviya A , How J , Tomlison J , Toh F , Roe M , Nightingale A , Garcia-Sueiro C , Herbert P , Jadon D , Norris P , Thomas J , Magsino J , Negoescu A , Raine T
Published: January 2020

Background

Biosimilar adalimumab became available in the UK in October 2018, with payers introducing a series of measures to drive the adoption of the ‘best value’ adalimumab.1 Consideration of value should include risk of loss of efficacy and adverse reactions, which might drive further biologic switches or ‘reverse switches’ to originator. Managing potential ‘nocebo effect’ requires high levels of patient engagement, whilst the presence or absence of citrate buffer may affect patient-reported discomfort, hence patient treatment perceptions.

Methods

Patients were switched to 2 different biosimilar adalimumabs, one buffered with citrate (ADA1) and one in a citrate-free buffer (ADA2). The choice of adalimumab biosimilar was made for clinical and economic reasons. Patients were informed of the switch to either ADA1 or ADA2 in advance via letter and at clinic visits. Patients who reported problems after switching were reviewed.

Results

A total of 744 patients were switched from originator adalimumab (ADA0) to ADA1 or ADA2. Rheumatology and dermatology patients were switched to ADA1, whilst gastroenterology patients were switched to ADA2, except for those with a latex allergy, where ADA1 was used (or ADA2 in a latex-free syringe). A total of 49 (6.6%) patients reported problems and a further switch of drug was judged necessary in 48 (Table 1). Switch failure was significantly more likely with ADA1 than ADA2 (7.7% vs. 1.8%; p = 0.006). The median time to switch failure was 97 days (range 5–196 days). The commonest reason for switch failure was disease flare (23 patients, 48%), followed by injection site pain or reaction (21 patients, 44%). Disease flare and injection site problems were more likely to be reported with ADA1 than ADA2 (flare: 23/583 vs. 0/161, p = 0.008; injection site pain 20/583 vs. 1/161, p = 0.06). For patients reporting disease flare, clinicians tended to select a reverse switch to ADA0, whilst for those with injection site problems, a further switch to a different biosimilar was the preferred approach; both strategies were effective at recapture.

Conclusion

In the context of an effective patient communication strategy, adalimumab biosimilar switching was associated with overall low rates of patient-reported problems in a large cohort. Despite an identical communication strategy, significantly higher rates of injection site problems and disease flares were seen between 2 different biosimilars, reflected in a higher need for further switches. These differences may impact the cost-effectiveness of any chosen strategy.

Reference
P522 Prior pharmacotherapy patterns among patients with IBD in the USA initiating biologic therapy
Authors: Bornheimer R , Hass S , NAG A , Oster G
Published: January 2020

Background

Treatment for inflammatory bowel disease (IBD: Crohn’s disease [CD] and ulcerative colitis [UC]) has shifted from symptom management using corticosteroids to targeted therapies such as tumour necrosis factor (TNF) inhibitors. An increase in therapeutic options warrants a better understanding of current treatment pathways. This study reports on the pharmacotherapy history of patients with CD and UC prior to initiation of an IBD-targeted biologic.

Methods

Using the US IQVIA™ Real-World Data Adjudicated Claims Database, we identified adults (≥18 years) with CD or UC who initiated biologics indicated for these diseases from 1 January 2016 to 30 June 2017. Patients were stratified based on the most recent biologic received; the date of initiation was designated the index date. Patients with < 12 months of continuous medical coverage prior to the index date were excluded. Patterns of prior IBD-related pharmacotherapy, in terms of the number and type of biologics, and time spent receiving the biologic, were examined in relation to the index biologic for the study period 1 January 2011 to 30 June 2017.

Results

In total, 3010 patients with UC and 5210 with CD were identified. Among patients with UC, 1285, 977, 587 and 161 initiated treatment with adalimumab, infliximab, vedolizumab and golimumab, respectively. Among patients with CD, 2634, 1436, 737, 241 and 162 began treatment with adalimumab, infliximab, vedolizumab, certolizumab and ustekinumab, respectively. Most patients beginning treatment with infliximab or adalimumab were biologic-naïve (UC: 79.9%, 89.3%, respectively; CD: 77.8%, 84.6%, respectively). Patients starting treatment with other biologics, however, had typically received at least one IBD-related biologic previously (Figure 1). Among patients who were not biologic-naïve at initiation of therapy, the mean total duration of prior biologic exposure was 17.8 months and 26.6 months for patients with UC and CD, respectively.

Conclusion

During the study period, anti-TNFs were the most commonly initiated biologics in both groups of patients. Although newer IBD-related biologics (i.e. vedolizumab and ustekinumab) are typically preceded by treatment with other biologics, most patients receiving an anti-TNF are biologic-naïve.
P537 Real-world long-term effectiveness of ustekinumab in Crohn’s disease: Results from the ENEIDA registry
Authors: Iborra Colomino M I , Beltrán B , Fernández-Clotet A , Iglesias Flores E , Navarro P , Rivero M , Gutiérrez A , Sierra-Ausin M , Mesonero F , Ferreiro-Iglesias R , Hinojosa J , Calvet X , Sicilia B , González-Muñoza C , Antolín B , González Vivo M , Carbajo A Y , García S , Martín-Cardona A , Surís Marín G , Martín-Arranz M D , De Francisco R , Cañete F , Carlos T , Gomollón F , Lorente R , Rodríguez-Lago I , Forés-Bosch A , Bernardos E , Ramos L , Delgado P , Hernández A , Van Domselaar M , Hervás D , Domènech E , Nos P
Published: January 2020

Background

There are limited data of long-term ustekinumab administered according to the doses recommended in the UNITI studies. The objective of this study was to assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn’s disease (CD) (LONG-CROHNUSK Study).

Methods

Multicentre study of CD patients starting ustekinumab at the recommended dose based on weight ~6 mg/kg IV week 0, 90 mg SC week 8 and maintenance 90 mg SC every 8 or 12 weeks and with 1 year of follow-up. Values for Harvey-Bradshaw Index (HBI), endoscopic activity, C reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs), surgeries and hospitalisations were documented. Potential predictors of clinical and endoscopic remission were examined.

Results

Four hundred and seven patients were analysed (Table 1). For the maintenance dose, ustekinumab 90 mg was administered SC every 12, 8 and 4 weeks in 56 (14%), 318 (84.5%) and 7 (1.5%) patients, respectively. An interval reduction was applied for 118 patients (29%). Before 52 weeks, treatment discontinuation occurred in 71 patients (17%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal (<250 μg/g) in the 44% and 54% of the patients at weeks 26 and 52, respectively. CRP returned to normal (<3 mg/l) in 36% and 37% of the patients at weeks 26 and 52 respectively. HBI, FC, and CRP values over time are shown in Figure 1. Of the 159 patients with endoscopy at 52 weeks, 25 (16%) were in remission and 58 (36%) presented mild activity. Thirty-eight (9.3%) patients worsened extra-intestinal manifestations and 33 (8%) their perianal disease. AEs were recorded in 54 patients, 73 were hospitalised and 53 had surgery. An association was shown for fewer previous anti-TNF agents and ileal localisation with clinical remission, and for endoscopic severity at baseline with poor response. No factors correlated with endoscopic remission.

Conclusion

This is the first study to show the real-world long-term effectiveness, endoscopic improvement and safety of ustekinumab administered according to the recommended induction regimen in a cohort of highly refractory CD patients.
P566 Assessing the efficacy of biologics in ulcerative colitis: A real-life, observational retrospective multicenter study using the propensity score analysis: The ‘A.U.R.O.R.A.’ comparison study
Authors: Cassinotti A , Mezzina N , Di Paolo D , Lenti M V , Bezzio C , Stradella D , Mauri M , Zadro V , Cortellezzi C , Ricci C , Casini V , Radice E , Massari A , Ardizzone S , Pastorelli L , Di Sabatino A , Manes G , Caprioli F , Vecchi M , Tari R , Occhipinti P , Fichera M , Invernizzi P , Parravicini M , Segato S , Pace F , Testoni P A , Tinelli C , De Silvestri A
Published: January 2020

Background

Until 2014, infliximab originator (Remicade, IFX-O) was the only biological treatment approved in Italy for ulcerative colitis (UC), followed by the sequential approval of adalimumab (ADA), infliximab biosimilar (CTP-13), golimumab (GOL) and vedolizumab (VDZ). Recently, comparative trials among these drugs provided conflicting results on their reciprocal superiority or equivalence.

Methods

In a retrospective, real-life, multicenter inception cohort study involving 11 Italian IBD tertiary centres, all consecutive patients with moderate-to-severe active UC, treated with ADA, CTP-13, GOL or VDZ after their post-marketing approval (2014–2018) were followed-up for 1 year or until relapse. All drugs were compared with each other and to patients treated with Remicade in 2013–2014 (reference group). The 80% power calculation of the study required at least 75 patients in each arm. A propensity score analysis was performed. The primary endpoint was the 1 year relapse-free, optimisation-free, steroid-free remission, defined as Mayo partial score ≤2, with bleeding subscore = 0, no relapse after first clinical remission and no optimisation with dose intensification or steroids courses. Multiple further secondary endpoints were analysed (Table 1).

Results

492 patients (ADA=90, CTP-13=105, GOL=79, VDZ=142, IFX-O=76) were included. Overall, 65% achieved clinical remission once during the follow-up, with IFX-O performing better than GOL and VDZ. The relapse rate was 24%, with the lowest rates with VDZ. The primary end-point was achieved in similar percentages in all groups, except for lower rates with GOL than IFX-O. IFX-O performed better than each other drug for other clinical outcomes (Table 1). Discontinuation for intolerance was similar among the drugs, but CTP-13 had more frequent adverse events (mainly infusion reactions) than ADA, VDZ and IFX-O.

Conclusion

Based on a strict definition of clinical remission, all biologics appear equally effective at 1 year, except for GOL vs. IFX originator. IFX-O appears more effective in multiple questionable clinical outcomes. IFX biosimilar had more adverse events than the other drugs. IFX originator should be used as the reference drug in head to head, controlled, comparison trials for current and future biologics in UC.
P568 An open-label, multicenter, phase ib, pharmacokinetic (pk) and safety study of a fimh blocker, Sibofimloc (TAK-018/EB8018), in patients with Crohn’s disease (CD)
Authors: Reinisch W , Hébuterne X , Buisson A , Schreiber S , Desreumaux P , Paillarse J M , Bonny C
Published: January 2020

Background

Sibofimloc (EB8018/TAK-018) is a gut-restricted orally administered, first-in-class, FimH blocker that targets FimH, a TLR4 receptor, expressed on E. coli and other Enterobacteriaceae in patients with CD. In a previous study, sibofimloc up to 1500 mg twice daily was well tolerated when administered to healthy subjects over a 14-day period. PK results indicated that sibofimloc was detectable in plasma at a very low level. The current study investigated the PK, safety, and pharmacodynamic effects of sibofimloc following 13 days of 1500 mg twice daily oral administration in patients with CD. Objectives of this study were to determine the PK (primary) and safety profiles, effects on inflammatory biomarkers, gut microbiome and on stool frequency and pain score.

Methods

We conducted a multicenter open-label study to enrol 8 adult patients with active CD (faecal calprotectin (FCP) ≥150 µg/g and/or ulcers at colonoscopy). Pregnant women were excluded. This study was divided into two parts. 1)Two patients received a single dose of 3000 mg sibofimloc followed, after a wash-out period, by a 13 day-period with1500 mg twice daily. 2)After review of data from these two patients, the 6 remaining patients received 1500 mg sibofimloc twice daily for a 13 day period.

Results

Cmax values for the 2 initial patients (after single dose 3000 mg sibofimloc) were 51.3 and 348 ng/ml respectively and allowed part 2 of the study. The main safety and PK data of an interim analysis after the first 4 patients had been treated with sibofimloc 1500 mg twice daily are presented in the table.

In a previous study in 7 healthy subjects, after 14 days sibofimloc 1500 mg twice daily, median Cmax[min-max] at Day14 was 49[19.2–86.6]ng/ml.

Conclusion

These preliminary data confirmed that sibofimloc was well tolerated. In the small subset of patients analyzed, there was a slightly higher plasma exposure and interpatient variability compared with what has been seen earlier in healthy subjects. The safety and PK data allowed the continuation of the clinical development program with the initiation of a phase 2 trial for postoperative maintenance in patients with CD.
P574 Incidence and indicators of suboptimal response to tumour necrosis factor antagonist therapy in Chinese patients with inflammatory bowel disease: Results from the EXPLORE study
Authors: Li J , Li Z , Hu P , Wen Z , Cao Q , Zou X , Chen Y , Wang Y , Zhong J , Shen X , Demuth D , Fedeeva O , Xie L , Chen J , Qian J
Published: January 2020

Background

Inflammatory bowel disease (IBD) patients may experience a suboptimal response to anti-tumour necrosis factor (TNF) therapy. In China, these data are limited. The EXPLORE study aimed to assess the incidence and indicators of suboptimal response to first-line anti-TNF agents in IBD patients in real-world practice in the newly industrialised countries.

Methods

The EXPLORE study was a multinational, retrospective chart review study. In the China subgroup, adult patients from 10 centres diagnosed with ulcerative colitis (UC) or Crohn’s disease (CD) and who initiated first anti-TNF treatment between March 2010 and March 2015, were included. The cumulative incidence (CI) of suboptimal response was assessed over 24 months since the anti-TNF initiation. The indicators of suboptimal response included: IBD-related hospitalisation, dose-escalation, discontinuation including switch to another anti-TNF, non-biologic therapy augmentation, or IBD-related surgery. Primary non-response (PNR) and secondary loss of response (SLOR) were defined as any suboptimal response indicator at <4 and ≥4 months after anti-TNF initiation, respectively.

Results

Overall, 287 first-line anti-TNF treated patients (35 UC; 252 CD) were included: male, UC 54.3% (n = 19), CD 74.6% (n = 188); mean (SD) age (years), UC 43.1 (14.2), CD 31.9 (11.3); median (min-max) disease duration (years), UC 1.0 (0–9), CD <1 year (0–21); median (min-max) follow-up (months), UC 27.6 (24–60), CD 40.0 (24–60). At 12 and 24 months, the CI of suboptimal response to first anti-TNF treatment was 51.4% and 75.7% in UC, 45.4% and 57.0% in CD, respectively (Figure 1). The median time to the first suboptimal response was 7.2 months in UC and 14.3 months in CD. The CI of PNR was 31.2% in UC and 33.7% in CD. The CI of SLOR was 29.4% and 64.7% in UC, 17.7% and 35.2% in CD at 12 and 24 months, respectively. The most frequent first suboptimal response indicator was ‘discontinuation of anti-TNF therapy’ in UC patients (56.3%) while for CD patients it was ‘IBD-related hospitalisation’ (56.1%) followed by ‘augmentation with non-biological therapy’ in both cohorts (UC 31.3%; CD 22.8%).

Conclusion

Approximately three-quarters of UC and over half of CD patients experienced a suboptimal response to their first anti-TNF agent at 24 months. Given the high unmet needs observed with anti-TNF therapies in China, IBD patients may benefit from greater optimisation of care and new biologic options.
P611 Provision of care for pregnant women with IBD in the UK - the current landscape
Authors: Moore E , Wolloff S , Glanville T , Selinger C P
Published: January 2020

Background

inflammatory bowel disease (IBD) results in increased rates of negative pregnancy outcomes; particularly in poorly controlled disease. We aimed to describe the current landscape of provision of antenatal care for women with IBD in the UK.

Methods

This cross-sectional study collected data on service set-up, on principles of care pre, during, and after pregnancy and on perceived responsibilities of clinicians. An online survey was distributed to all gastroenterology units in the UK.

Results

Data were provided for 97 of 273 IBD units. Pre-pregnancy counselling was not available in 7%, offered routinely (39%), or on request (54%) but predominantly (91%) in an ad-hoc fashion rather than in a dedicated set-up. Ninety-two per cent of units provided a nominated gastroenterology consultant during pregnancy. In 86% of this was the patient’s usual consultant rather than a consultant with expertise in pregnancy (14%). Combined clinics with obstetricians and gastroenterologists were offered in 14% of units only, but more often in academic rather than district hospitals (24% vs. 7%; p = 0.043) Otherwise, communication with obstetrics was ‘as and when required’ in 51% of cases. Patients were reviewed either every trimester (55%), monthly (15%) or ‘only when required’ (30%). The majority of respondents thought gastroenterologists should be involved in decisions regarding routine vaccinations (70%), breastfeeding (80%), folic acid dosage (61%), and VTE prophylaxis (53%). Sixty-five per cent of participants thought that gastroenterologists should be involved in decision-making regarding the delivery method. Regarding IBD indications for elective caesarean section, 94% of participants recommended these for active peri-anal disease, 30% for previous but healed peri-anal disease, 56% for ileo-anal pouch and 20% for previous abdominal and/or pelvic surgery.

Conclusion

In a nationwide survey on the provision of antenatal IBD care we found considerable variation in all aspects of service provision, particularly the availability of expertise and specialist services. We have detected areas of poor care (review only when required, communication ad-hoc only, poor provision of dedicated pre-pregnancy counselling). A significant minority of IBD units also felt that they do not need to provide input into areas such as VTE prophylaxis, delivery method and folic acid dosing. IBD indications for caesarean section seem to be poorly understood by a sizable minority. A basic framework to inform service set-up, and better education on the available clinical guidance for clinicians, is required to ensure consistent identification and review of patients and high-quality care.
P613 Use of adalimumab biosimilar ABP 501 in Crohn’s disease: A real-life experience
Authors: Ribaldone D G , Vernero M , Pellicano R , Morino M , Saracco G M , Astegiano M
Published: January 2020

Background

The use of biologics in Crohn’s disease (CD) entails an increasing cost on national health systems. The use of biosimilars of adalimumab in CD is based on the concept of extrapolation of the results obtained in rheumatoid arthritis and in psoriasis, while no study about the efficacy and safety on CD of the biosimilars approved in Europe have been published. The aim of our study was to analyse, for the first time in literature, the effectiveness and safety of ABP 501 in CD patients naïve to adalimumab and its retention rate in CD patients who switched from adalimumab originator.

Methods

We performed an observational study on patients prospectively followed at the gastroenterology clinic of the Turin University Hospital. Inclusion criteria are (a) CD diagnosed according to ECCO criteria; (b) age ≥16 years; (c) initiation of therapy with ABP 501. Exclusion criterian is follow-up duration of less than 3 months for adalimumab-naïve patients, less than 6 months for patients who switched to ABP 501. Primary outcomes were (a) for patients treated with ABP 501 as first adalimumab: clinical response rate at 12 weeks and (b) for patients who switched to ABP 501: drug retention at 24 weeks. Secondary outcomes were (a) clinical remission rate at week 12 (for patients treated with ABP 501 as first adalimumab); (b) HBI and CRP reduction at week 12 (for patients treated with ABP 501 as first adalimumab), no significant change in HBI and CRP values at week 24 (for patients who switched to ABP 501); (c) analysis of predictors; and (d) adverse events incidence.

Results

Eighty-seven patients were included, of which 25 were naïve to adalimumab originator and 62 were switched to ABP 501. In adalimumab-naïve patients, the clinical response at 3 months was 60% (15/25), clinical remission at 3 months was 56% (14/25). At 6 months, 95.2% (59/62) of the patients switched to ABP 501 were still in therapy, without a significant increment of clinical activity (Harvey–Bradshaw Index from 3.4, 95% CI = 2.4 – 4.4, to 3.8, 95% CI = 2.7 – 4.9, p = 0.23), and inflammatory biomarker (CRP from 4.2 mg/l, 95% CI = 2.5 mg/l – 5.9 mg/l, to 3.6 mg/l, 95% CI = 2.2 mg/l – 5 mg/l, p = 0.32). No unexpected adverse events occurred during the study period.

Conclusion

Our results support ABP 501 as an efficacious and well-tolerated drug, at least in the short-term, and its interchangeability with its originator in the treatment of CD.
P637 PERFUSE: A french non-interventional cohort study of infliximab-naive and transitioned patients receiving infliximab biosimilar SB2; An interim analysis
Authors: Bouhnik Y , Fautrel B , Desjeux G , Freudensprung U , Brigui A , Addison J
Published: January 2020

Background

SB2 is approved in the EU as infliximab (IFX) biosimilar, having demonstrated bioequivalence and similar efficacy, safety and immunogenicity as the reference. Little evidence is published on real-world use of SB2 in patients who are either IFX-naïve, or transitioned from originator or another IFX biosimilar. PERFUSE is an ongoing non-interventional study of 1,374 patients receiving SB2 as routine therapy at 12 gastroenterology sites across France, with objectives to describe clinical characteristics, immunogenicity and SB2 persistence over 12 months.

Methods

Eligible adult patients are diagnosed with Crohn’s disease (CD) or ulcerative colitis (UC) and initiated SB2 in routine clinical practice after September 2017 as their first IFX or transitioning from treatment with reference IFX or another IFX biosimilar. Data are captured from routine patient records for up to 12 months (M12) following initiation. Outcome measures include persistence on SB2, clinical characteristics at baseline (time of initiation of SB2) and disease scores (Harvey–Bradshaw Index (HBI), Simple Clinical Colitis Activity Index (SCCAI)) and SB2 dose over time.

Results

This interim analysis (IA) includes 755 patients (580 with CD; 59 IFX-naïve, 521 transitioned from prior IFX: 175 with UC; 33 IFX-naïve, 142 transitioned from prior IFX). In the 663 patients with prior IFX, no clinically relevant difference in disease score from baseline to M12 was observed; mean individual change was −0.3 (95% CI −0.8, 0.1) and -0.2 (95% CI −0.6, 0.3) in the CD cohort transitioned from reference IFX (n = 157) and biosimilar IFX (n = 83), respectively; −0.3 (−1.1, 0.4) and 0.0 (-0.9, 0.9) in the UC cohort transitioned from reference IFX (n = 41) and biosimilar IFX (n = 26), respectively. Mean (95% CI) SB2 dose (mg/kg), was similarly unchanged from baseline to M12: 7.2 (5.0, 10.0) and 7.6 (5.0, 10.0) in patients with CD transitioned from reference IFX or from biosimilar IFX; 7.0 (5.0, 10.0) and 7.3 (5.0, 10.0), 7.5 (5.0, 10.0) and 7.7 (5.0, 10.0) in patients with UC transitioned from reference IFX or biosimilar IFX, respectively. By data extraction date (23 October 2019), 374 patients with CD and 105 with UC had reached M12; persistence on SB2 was 92.2% (95% CI 89.1, 94.7) and 90.5% (95% CI 83.2, 95.3) in CD and UC, respectively. Reasons for discontinuation (n) were: adverse event (9), primary loss of response (7), secondary loss of response (12) and unspecified (16).

Conclusion

This IA indicates that patients with IBD can be successfully and safely transitioned from reference or biosimilar IFX to SB2, with no loss of disease control and without need for dose escalation. Over 90% of transitioned patients continued SB2 treatment at M12 post-initiation.
P645 Adalimumab drug monitoring is superior to empirical treatment adjustment in inflammatory bowel disease
Authors: CURRAIS P , Fernandes S , Bernardo S , Correia L , Gonçalves A R , Baldaia C , Moura Santos P , Valente A , Tato Marinho R
Published: January 2020

Background

Anti-TNF blockers are effective drugs in the treatment of inflammatory bowel disease (IBD). Therapeutic drug monitoring (TDM) of Adalimumab (ADA) may potentially improve clinical outcomes in this setting, but data are still scarce.

Methods

To compare ADA TDM and empirical treatment adjustment (ETA) in patients with IBD. Outcomes were evaluated at 2 years and included hospitalisation, surgery, treatment discontinuation, endoscopic remission and treatment failure (any unfavourable event).

Single-centre retrospective study, including patients under ADA therapy.

Results

103 patients were included, 86 with Crohn’s disease and 17 with ulcerative colitis. 52.4% male, mean age 28.5 (18–72). 56 patients received ADA TDM and 47 ETA. At 2-years, rates of treatment escalation (57.1% vs. 21.3%, p <0.001), mucosal healing (69.6% vs. 48.9%, p =0.032) and treatment discontinuation (17.9% vs. 4.3%, p =0.032) favored the TDM group. For TDM and ETA respectively, there was no statistically significant difference regarding need for hospitalisation (12.5% vs. 21.3%, p = 0.232), surgery (5.4% vs. 14.9%, p =0.103) and treatment failure (26.7% vs. 34.5%, p =0.395).

Conclusion

Our results suggest a benefit of TDM in achieving higher rates of mucosal healing The higher rates of treatment discontinuation suggest that TDM improves drug selection as patients switched unhelpful treatment earlier.
P677 It’s time to grow up: what is it like to transition from the paediatric to adult inflammatory bowel disease service?
Authors: Keightley P , Prematunga R , Hoffmann P , Subramaniam K
Published: January 2020

Background

inflammatory bowel disease (IBD) is a chronic disease with an increasing incidence in the paediatric population. We explored the experiences of two groups of patients, those who transitioned directly from the paediatric to the adult service before the transitional IBD clinic was established, referred to as ‘adult’ and those who engaged in the new transitional clinic, referred to as ‘transitional’.

Methods

Sixteen (8 in each group as described above) out of 20 suitable patients participated. Patients were administered the IBD Questionnaire (IBDQ), Kessler Psychological Distress Scale (K10), Patient- Doctor Relationship Questionnaire (PDRQ-9) and Stressful Life Events Questionnaire. A semi-structured interview was administered to patients and carers about their experiences of diagnosis, paediatric care, transition to adult services and adult care.

Results

The average age of participants in both groups was 17. The transitional clinic had a higher proportion of Crohn’s disease. In the adult group, there were more males and the reverse in the transitional group. The adult clinic patients had more active disease, use of steroids, and emergency department presentations. The mean CRP of 36 mg/l at first visit to the adult clinic improved to 12 mg/l, at last, follow-up whereas mean CRP at first and last visit to the transitional clinic remained at 2 mg/l. Both clinics had similar rates of compliance and attendance. In the transitional and adult clinics respectively the mean IBDQ was 193 (SD=31) and 174 (SD = 22) with higher scores reflecting better health-related quality of life, the K10 mean score was 16 (SD = 7.5) and 17.5 (SD = 4.3) indicating a moderate level of distress, the PDRQ-9 mean scores were 4.3/5 (SD = 0.75) and 4.8/5 (SD = 0.4) indicating good therapeutic relationships. Both groups reported a similar number of stressful life events. Key themes were identified in both patient and carer interviews: (1) Diagnosis and illness: Diagnostic uncertainty, frustration at the diagnostic process, and the importance of finding a doctor you trust. (2) Maturity: growing up fast for some and seeking independence, growing up slowly for others while non-ill peers matured faster. (3) Carer adjustment: The central role of mothers and fathers as carers. Some adolescents feel highly responsible for their parents’ and families’ well-being.

Conclusion

Patients with IBD and their carers face particular difficulties during the period of transition from a paediatric to adult service. These are factors specific to the illness and factors related to maturation and development. There should be flexibility around maturity which is not rigidly age-based but instead based on the specific developmental needs of different families and adolescents.
P696 The usefulness to treatment enhancement for the patients of ulcerative colitis with clinical remission diagnosed as Mayo endoscopic subscore 1
Authors: Kubota Kajiwara M , Uchiyama K , Azuma Y , Yasuda R , Takayama S , Takagi T , Naitoh Y
Published: January 2020

Background

In many clinical trials of ulcerative colitis (UC), Mayo endoscopic subscore (MES) has been used to diagnose mucosal healing to evaluate the effectiveness of various treatment. Although both MES 0 and MES 1 were defined as the endoscopic mucosal healing, several studies reported that the risk of clinical relapse was significantly higher in the patients diagnosed as MES 1 compared with MES 0. However, it has not been established the beneficial effect to escalate the treatment for the patients diagnosed as MES 1 to avoid clinical relapse. In the present study, we retrospectively investigated the effectiveness about the escalation of treatment for UC patients with clinical remission diagnosed as MES 1.

Methods

A total of 68 patients with UC diagnosed as clinical remission (4 and under of Lichtiger CAI score) between April 2014 to October 2019 were enrolled in this study. All patients were endoscopically diagnosed as MES 1 and observation period was 12 months from the time of endoscopy. Relapse of UC was defined as the need for more aggressive treatment for UC due to aggravation of clinical symptoms or endoscopic findings. The relapse ratio was compared between the patients who continued the same treatment and the patients who had enhanced treatment. Enhanced treatment was defined as additional oral medicine or local preparations including enemas, suppositories, and foams within 3 months from endoscopic examination.

Results

In 68 patients, 12 patients were received enhanced treatment and 56 patients were continued the same treatments. There were no significant differences in clinical background between the two groups such as mean age (enhanced treatment group vs. same treatment group: 47.9 years vs. 42.9 years), disease type, disease duration (110.3 months vs. 94.8 months), and disease activity (Lichtiger CAI score: 2.5 vs. 2.8). The group of the enhanced treatment included 8 patients with oral 5-aminosalicylates escalation and 4 patients with additional local preparations. The relapse ratio was higher in patients with same treatment group (0%) compared with enhanced treatment group (14.3%).

Conclusion

Our results indicate that the enhancement of the treatment for UC patients with clinical remission diagnosed as MES 1 is effective to avoid relapse.