bluuebunny/crossref_metadata_2025_split huggingface dataset:
P497 Is mucosal healing sufficient paramater for anti-TNF discontinuation?
Authors: Knezevic T , Milic M , Kalaba A , Sreckovic S , Stopic B , Svorcan P , Markovic S 
Published: January 2020

Abstract

Background
Long-term treatment with biologic therapy alongside with immunomodulators in patients with inflammatory bowel disease (IBD) can be associated with severe side effects. Nowadays, there is not a clear recommendation for de-escalation of therapy in patients on biologic treatment. The aim of the study was to evaluate relapse rate in 4 ili 2 years follow-up in patients with mucosal healing after two years of anti-TNF treatment, regardless achieved histological remission.

Methods
52 patients with IBD after two years treatment with anti-TNF agents (Infliksimab (IFX) and Adalimumab (ADA)) and achieved mucosal healing, were enrolled in this retrospective study. Mayo endoscopic sub-score (0,1) and SES (&lt;2) was used to define mucosal healing in UC and CD patients, respectively. For the assessment of histological activity Nancy and Global Histologic Disease Activity Score (GHAS) were used. Histologic remission was defined by Nancy’s score ≤ 1 and GHAS ≤ 4. Data were collected for 4 years follow-up period after discontinuation of anti-TNF agents. Statistical analysis was carried out using SPSS 20.0 (Chicago, IL).

Results
From 52 patients 40.38% (21/52) patients had UC, and 59.61 % (31/52) had CD with an average disease duration of 11.57 (SD ± 6.28) years. Gender distribution was relatively equal, 46% men (24/52), with an average age of 40.66 (SD ± 11.15) years. All of the patients were on anti-TNF therapy and had mucosal healing at the moment of discontinuation, 55% (29/52) were on IFX, 35% (23/52) were on ADA, respectively. 48.07% (25/52), were with pathohistological remission of disease. In 4 years follow-up after anti-TNF therapy discontinuation, 59.61% (31/52) relapsed, with an estimated period of relapse time of 15.4 (SD ± 9.83) months. Using Spearman`s correlation moderate relation was revealed between histological activity and relapse (rho 0.467, p &lt; 0.001). Probability of relapse within 4 years in this group of patients with histologically active disease was higher (p &lt; 0.01, OR 2.72, 95% Cl 1.24–5.92).

Conclusion
Achieving both, endoscopic and histological remission, may be a good parameter in making a decision when to de-escalate anti-TNF therapy.
P501 Thiopurine withdrawal in patients with Crohn’s disease: the SURESTE study
Authors: Sánchez Rodríguez E , Sánchez Aldehuelo R , Guardiola J , Gutiérrez Casbas A , Domènech E , Bermejo F , Van-Domselaar M , Mesonero Gismero F , Suris G , Muñoz Perez R , Mañosa M , Jiménez Márquez L , Algaba García A , López sanroman A 
Published: January 2020

Abstract

Background
Thiopurine (TP) withdrawal in patients with Crohn’s disease (CD) in clinical remission (CR) is controversial. Our aim was to describe the evolution of CD patients in CR who discontinued TP prescribed to maintain a remission previously achieved with medical treatment, and to detect predictors of reactivation after withdrawal.

Methods
Multicentric observational retrospective study including CD patients in RC under TP treatment, who electively discontinued TP. Relapse was defined as the need to start any specific treatment for CD, including surgery. Informed consent was obtained from the inclusion in the Eneida database.

Results
We included 78 patients (52.6% females, age 45(19–77) years) of whom 57 presented an inflammatory, 12 a stricturing and 9 a penetrating behaviour; 31 patients had terminal ileum involvement, 9 colonic, 36 ilecolonic, and 2 ileocolonic plus upper gastrointestinal involvement, whilst 17 also had perianal disease. Mean disease duration was 13.47 (3.02–35.02) years. 48.7% had never smoked whilst 24.4% were active smokers. TP was started to maintain remission previously achieved with medical therapies in 78 patients (100%). Median azathioprine dose was 2.11 (1.3–2.6) mg/kg/d, and of 6-mercaptopurine (6MP) 1.44 (1–2) mg/kg/day. The median duration of TP treatment was 52.79 (3–268) months and of steroid-free remission 49.41 (1–177) months. Reasons for TP withdrawal were: patient choice/request in 20 (25.6%), physician proposal in 28 (25.7%), drug-related adverse events in 19 (24.4%) and miscellaneous in 11 (14.1%). By the time of TP discontinuation, median CRP was 5.08 mg/l (0.1–157.9), fecal calprotectin(FC) 282.38 µg/g (2.4-4430) and a mean 0.45 (0–4) in Harvey–Bradshaw Index (HBI); those who relapsed presented median CRP of 15.31 mg/l (0.1–125.31), fecal calprotectin (FC) 462.22 µg/g (90–1240) and a mean 5.46 (0–15) in HBI. These differences were statistically significant. During a 5.08 (0.12–13.05) years follow-up, 38 (48.1%) patients relapsed, with treatment duration being the only factor associated to risk of relapse (Or = 0.659 IC95 0.43–0.98, p = 0.04) in the multivariant analysis (IMAGE1).

Conclusion
Thiopurine withdrawal in the context of sustained remission in CD is associated with relapse in almost half of the patients after a median follow-up of 5 years. Thiopurine treatment duration of shorter than 5 years was shown to carry greater risk for relapse.
P507 Ustekinumab: Medium-term outcomes from a UK multicentre real-world cohort
Authors: Gadhok R , Fragkos K , Honap S , Hassan J , Whiteley L , Ibarra A , Burgess N , Vega R , Seward E , Mehta S , McCartney S , Bloom S , Parkes G , Irving P , Lindsay J O , Kok K B , Rahman F 
Published: January 2020

Abstract

Background
Ustekinumab is effective at inducing and maintaining remission of Crohn’s disease (CD) in clinical trials. However real-world practice may vary regarding use of concomitant immunomodulator (IM), dosing schedule and patient selection. We present the largest UK real-world, multi-centre study of effectiveness.

Methods
The cohort comprised adult patients initiated on ustekinumab for CD from October 2016–18 at 3 tertiary London centres. Clinical endpoints were (i) remission (Harvey Bradshaw Index (HBI) ≤4) (ii) response, (reduction in HBI of ≥3 or sustained HBI≤4 points) at 3, 6 and 12 months. Biological endpoints were remission and response (CRP &lt;5mg/l in patients with a baseline CRP&gt;5mg/l, and 50% reduction in CRP, respectively).

Results
211 patients were included (Table 1), of whom 207 (98%) were biologic exposed and 59 (28%) had failed 3 biologics. All patients received i.v. induction and 203 (96%) received a s.c. dose at week 8. At 6 and 12 months, 133 (74.8%) and 109 (73.6%) patients, respectively, were on 8 weekly dosing. Dosing schedule did not impact clinical and biological outcome at 6 and 12 months.

Discontinuation occurred in 4 (1.9%), 20 (9.5%) and 50 (23.7%) patients by 3, 6 and 12 months respectively. Reasons for stopping included: drug reactions (4(1.9%)), partial response (4 (1.9%)), loss of response (10 (4.7%)) and primary non-response. (24 (11.4%)). Clinical and biological outcomes at 3, 6 and 12 months are shown in Figure 1. Adverse events occurred in 27 (12.8%) patients. IM were prescribed in 49 (23%) at baseline and continued in 46 (21.8%), 36 (17.1%), 27 (12.8%) at 3, 6 and12 months respectively. There was no significant difference in median persistence (months) on ustekinumab between patients who were on an IM at baseline vs. those not (15.2 (95% CI 0–32.2) vs. 23.3 (17.3–29.4) months, p = 0.4). Likewise, there was no significant difference in clinical or biological outcome between patients with colonic vs. ileocolonic or ileal disease. Finally, there was no significant difference in median persistence on ustekinumab between patients with and without a history of perianal disease (19.5 (95% CI 9.2–29.8) vs. 22.9 (18.6–27.2) months, p = 0.8).

Conclusion
Ustekinumab is effective in a real-world cohort. In keeping with trial data, we did not find evidence of improved outcomes with the use of a concomitant IM, nor differential outcomes when considering perianal and isolated colonic disease.
P518 Ulcerative colitis drug development success rates are higher than the industry average
Authors: Georgiev G , Hussain F , Copeman M , Delegge M , Gallagher M B , Stewart T , Reinisch W 
Published: January 2020

Abstract

Background
Given the increasing costs of drug development, coupled with low success rates, there is a need to both develop better predictive models and elucidate causes of failure. However, for indications such as ulcerative colitis, a baseline does not presently exist. In this paper, we review trends in drug development and establish a baseline for ulcerative colitis.

Methods
We used BiomedTracker to obtain information about the number of compounds, which were in development for ulcerative colitis between 2005 and 2018. We counted the number of compounds, which had reached a particular phase, had been discontinued during this phase, had successfully passed it or had been still in this phase. Success rates were derived for the different phases of drug development for all 73 candidate drugs and divided by type of molecule and type of company. A success rate was calculated by dividing the number of drugs successfully completing a particular phase by the sum of the number of drugs which were discontinued during this phase and the number of compounds that completed positively a phase. The likelihood for approval (LOA) for each phase was calculated by multiplying the success rate for the respective phase with the success rates of next stages of development.

Results
The success rate in phase I was 96 %, in phase II 53 % and in phase III 76%, while the respective LOA was 0.39, 0.4 and 0.76. Table 1 demonstrates the success rates and LOA by type of compound(New molecular entity (NME), Biologic, non-NME) and type of company (big, mid-size, emerging).

Conclusion
The general industry success rates and LOA for phase I is 64%, for Phase 2 30%, and for phase 3 60% while the LOA from phase I is 10%. These data are published by Michael Hay and co-authors in Nature in January 2014. The success rates in UC drug development are therefore higher than the overall industry success rates.
P523 Improvement of quality of life and continence in patients with distal ulcerative colitis treated by mesalazine: QUARTZ study
Authors: Paupard T , Gonzalez F , Siproudhis L , Peyrin-Biroulet L 
Published: January 2020

Abstract

Background
There is no robust data which analysed quality of life, functional disability and continence of patients with distal UC. QUARTZ is the first prospective study in this situation.

Methods
Observational, prospective and multicentric study involving public and private French gastroenterologist to recruit patients with mild to moderate (Mayo score ≥ 3 and ≤ 10) active proctitis or proctosigmoiditis (&lt;20 cm) and under mesalazine for induction treatment. The patients followed for 12 months (±2 months). The primary objective was the quality of life evaluated by Short Inflammatory Bowel Disease (SIBDQ) at 8 weeks (±4 months). The functional disability and incontinence have been evaluated by IBD-Disability Index and Cleveland questionnaires.

Results
From December 2015 to November 2016, 117 patients were recruited. Data of 93 patients have been analysed and results are reported on Table 1. Among the 93 patients, 75 (81%) reached a clinical remission at week 8 with a SIBDQ score improvement of 6.7 ± 7.1 point (p &lt; 0,001). Treatment adherence during the induction period was non-compliance for 76 patients (81%): 17 (18%) patients stopped treatment before W8 (all those patients received rectal formulation). After induction treatment, 72 (77%) patients received maintenance treatment. 11 (12%) patients reported adverse event not linked to the treatment.

Conclusion
For patients with distal ulcerative colitis treated by mesalazine, quality of life, functional disability and continence have been improved at 8 weeks of treatment despite a poor adherence.
P531 A retrospective audit of the inflammatory bowel disease specialist nurse-led telephone advice service
Authors: Watters C , Lloyd W , Porteous M , Mohamed M , Kari S , Nelson E , Saravanan R 
Published: January 2020

Abstract

Background
Inflammatory bowel disease affects more than 300 000 people in the UK. The aims of the audit were to review the current use of a telephone service provided by the IBD specialist nursing team in a DGH with a view to better funding and further development of the facility.

Methods
The letters generated from each phone call between January and February 2018 were collected and a sample assessed for outcomes directly related to the consultation. Outcomes were subtyped into a change in medical treatment, referral for investigation, referral to another specialist or arrangement of an urgent clinic appointment or hospital admission. Each phone consultation was also assessed as to whether it had avoided an attendance to the GP or hospital via A&E or acute medicine.

Results
The two-month period yielded 491 phone calls, of which 100 letters were reviewed of which 56 (56%) had ulcerative colitis (UC), 44 (44%) had Crohn’s disease (CD). Male users comprised 36% (vs. 64% females) and the age of callers ranged from 19 to 84 years (median age 44 years). Of the UC patients, 45 patients (80.4%) had been diagnosed over 2 years previously with two (3.6%) having been diagnosed within the preceding 3 months (CD patients 34 (77.3%) &gt;2 years previously and three (6.8%) within the last 3 months). The phone consultations led to a change in medication in 49 cases (49%). Phlebotomy and/or faecal calprotectin testing was requested for 59 patients (59%) following the phone call and a further 17 (17%) were discussed with a consultant, although only 8 (8%) required an IBD nurse-led or gastroenterology consultant-led clinic (six and two patients, respectively). Nine patients (9%) went on to have cross-sectional imaging or ultrasound with contrast and 7 (7%) were referred for endoscopic assessment. The overall complexity of the consultation was assessed by the number of services referred to/requested. Thirty-four patients (34%) merely required reassurance or verbal advice whereas two cases (2%) led to five distinct referrals or investigation requests (one service 33 (33%), two service 20 (20%), three service 9 (9%), four service 3 (3%)). Each phone call was assessed as to whether it had likely avoided attendance elsewhere. This included general practice (25 cases (25%)), accident and emergency (2 (2%)), IBD nurse clinic appointment (41 (41%)) or consultant clinic appointment (6 (6%)).

Conclusion
(1) Our audit shows that the IBD nurse-led telephone service is extremely demanding, with a large volume of calls. (2) Remote management of patients could be facilitated by the telephone nurse-led hotline advice service leading to a reduction in healthcare costs, avoiding face-to-face consultations and managing patients as per their personalised needs.
P542 The effect of age on infliximab pharmacokinetics in patients with inflammatory bowel disease
Authors: Kantasiripitak W , Verstockt B , Lobatón T , Thomas D , Gils A , Vermeire S , Ferrante M , Dreesen E 
Published: January 2020

Abstract

Background
Data remain scarce in terms of efficacy and safety of infliximab (IFX) treatment in elderly patients with inflammatory bowel disease.1 Our aim was to employ a population pharmacokinetic (popPK) model to improve our understanding of factors impacting variability in IFX exposure in elderly patients with ulcerative colitis (UC) and Crohn’s disease (CD).

Methods
IFX concentration–time data during induction therapy (week 2, 6 and 14) of 104 patients were obtained from a retrospective case–control study2 (n = 79) and a single centre database search (n = 25) at our institution. Patients ≥65 years old were categorised as elderly. A popPK model was developed using NONMEM 7.4. Relationships between IFX exposure and the first endoscopic remission (ER) assessment after the start of IFX therapy (absence of ulceration [CD] and Mayo endoscopic sub-score ≤0 [UC]) were evaluated.

Results
Median age was 62 years (IQR 38–68). A total of 46 of 104 patients (44%) were elderly. A one-compartment model with linear clearance showed adequate descriptive and predictive ability. The estimated popPK parameters (typical value [%RSE]) were clearance CL (0.346 l/day [4%]) and volume of distribution V (6.42 l [5%]). The elimination half-life of IFX in the elderly was not significantly different from the non-elderly (12.6 days vs. 11.4 days, p = 0.356). IFX clearance was higher with the presence of antibodies to IFX (ATI; drug-tolerant assay; 32% higher), higher fat-free mass (FFM; 1.4% per kg), lower serum albumin (4.5% per g/l), and younger age (0.6% per year). These covariates explained 10% of interindividual variability (IIV) in IFX CL. However, 33% of the variability remained unexplained. Contrary to Paul et al.3, proportions of patients with ATI were not significantly different between elderly and non-elderly (13% [6/46] vs. 14% [8/58], p = 1.000). FFM and serum albumin were significantly lower in elderly patients (p = 0.007 and p = 0.0004, respectively). Due to the large remaining IIV, IFX exposures (trough concentrations and estimated area under the PK curve) were not significantly different between elderly and non-elderly (Figure 1). A total of 19/72 patients (26%, 32/104 had no endoscopy data) achieved ER. There was no significant difference between the proportion of elderly and non-elderly with ER (p = 1.000). IFX trough concentrations at w6 were significantly higher in patients achieving ER (p = 0.016).

Conclusion
Older age is an independent predictor of lower clearance. However, the effect of age did not pronounce on infliximab exposure in our elderly patient cohort as a result of confounding effects of fat-free mass and serum albumin.

References
P552 Withdrawal of immunomodulator medications (IM) in children with inflammatory bowel disease on combination therapy of IM and biologics
Authors: Chandrakumar A , Carroll M , deBruyn J , Jacobson K , Huynh H , Wine E , Lawrence S , El-Matary W 
Published: January 2020

Abstract

Background
Anti-tumor necrosis factor (anti-TNF) antagonists such as infliximab (IFX) are widely used for the treatment of inflammatory bowel disease (IBD). Early studies suggested that combination therapy with IFX and an immunomodulator drug (IM) such as azathioprine (AZA) or methotrexate (MTX) may help in optimising biologic pharmacokinetics, minimising immunogenicity, and improving outcomes. On the other hand, IM especially AZA, may increase infection and cancer risks with no clear evidence on long-term benefits of combination therapy. As such, stopping IM and continuation of an anti-TNF agent as a monotherapy in patients in remission seem to be a sensible strategy. However, there is no evidence to prove the efficacy of this strategy. The aim of this work was to examine frequency and factors associated with the first relapse after IM withdrawal in a cohort of children with IBD on combination therapy.

Methods
In a retrospective multicenter pediatric study, we determined the percentage of patients and investigated potential factors associated with the first relapse in a cohort of children and young adults with IBD on combination therapy of anti-TNF and IM after stopping IM. Cox regression analysis was used to assess factors associated with IBD relapse following IM withdrawal.

Results
A total of 79 patients (42, males, 62 Crohn’s disease) with 74 (93.7%) on IFX were included. In addition to the anti-TNF agent, 33 (41.8%) were on AZA and the rest were on MTX. The median duration of combination therapy was 2.0 (IQR 1.2–2.8) years. All participants were in clinical remission at the time of IM withdrawal. The median duration of follow-up after IM withdrawal was 11.0 (IQR 5.0–16.2) months. Only 8 (10.1%) patients relapsed over that period of follow-up. Age, sex, disease phenotype at diagnosis, family history of IBD, type of IM, and biochemical markers and clinical disease activity indices prior to IM stoppage did not predict a future relapse. Among those with CD on IFX who maintained remission, the median last IFX trough level before IM withdrawal was 6.25 Ug/ml (IQR: 4.04–8.70) vs. 3.8 Ug/ml (IQR: 2.40–11.6) in those who relapsed (p = 0.4).

Conclusion
Over short-term follow-up, the majority of children on combination therapy of IM and an anti-TNF agent remain in clinical remission after IM withdrawal.
P556 Long-term probability of retreatment with anti-TNF therapy after discontinuation based on mucosal healing in inflammatory bowel disease
Authors: Luque Carmona A M , García Ortíz J M , Nuñez Ortiz A , De la Cruz Ramírez M D , Herrera Justiniano J M , Leo Carnerero E 
Published: January 2020

Abstract

Background
To evaluate the need for retreatment with anti-TNF due to relapse after discontinuation based on mucosal healing in inflammatory bowel disease (IBD), as well as the influencing factors and the response to reintroduction.

Methods
Descriptive retrospective study of IBD patients in whom anti-TNF treatment was discontinued after mucosal healing had been proved, between June 2009 and May 2016. Demographic and phenotypic characteristics, biologic and immunomodulator (IM) therapy history, laboratory markers and histopathologic evaluation were noted. We evaluated the relapse rate after discontinuation of anti-TNF, as well as the need for reintroduction and its success rate.

Results
We included 100 patients, 69 of them affected by Crohn’s disease (CD), 29 with ulcerative colitis (UC) and 2 unclassified colitis. From those with CD, inflammatory behaviour (62%) and ileocolonic localisation (53%) were the most frequent conditions. Seventy-four per cent of UC patients had pancolonic involvement. Biological therapy had been indicated because of corticodependence in 66% (vs. 32% corticorefractoriness). The anti-TNF drug was infiliximab in 60 patients, adalimumab in 38, 1 certolizumab and one had been treated with golimumab. Endoscopic biopsies showed quiescent disease in 63 of 83 patients. Eighty-three per cent of patients were treated with IM after removal of anti-TNF. After a mean follow-up of 57 months, 63 patients relapsed, 52 of them needing anti-TNF reintroduction. Reintroduction rates at 12, 36 and 60 months were 19.5%, 43.5% and 52% respectively with a response after the re-treatment of 76,6%. Univariant analysis showed a higher risk in CD (61 vs. 31%, p = 0.008). Within the CD patients, the risk of reintroduction was lower in A3 (30 vs. 66%, p = 0.03) and B2 (31 vs. 69%, p = 0.006) patterns, and higher if the indication had been corticodependence (68% vs. 37%, p = 0.02). Multivariant analysis confirms the protective effect of B2 behaviour and worse outcomes for corticodependence antecedent. Considering UC, the retreatment probability was superior for those patients without IM therapy after anti-TNF discontinuation (57 vs. 22%), although this association did not reach statistical significance (p = 0.08).

Conclusion
The risk of needing reintroduction of anti-TNF therapy after mucosal healing in IBD is around 50% in 5 years, being superior in CD patients. Reintroduction success rate is 76%. In CD, this risk is higher when the reason for starting anti-TNF was corticodependence, and much lower when stricturing/fibrotic pattern predominates. For UC patients, anti-TNF drugs should not be stopped if IM therapy cannot be held.