bluuebunny/crossref_metadata_2025_split huggingface dataset:
P494 The efficacy and safety of adalimumab for patients with moderately to severely active ulcerative colitis and predictors of response in Korea
Authors: Shin Shin S , Park S J , Kim Y , Im J P , Kim H J , Lee K M , Kim J W , Jung S A , Lee J , Kang S B , Shin S J , Kim E S , Kim Y S , Kim T O , Kim H S , Park D I , Kim H K , Kim E S , Kim Y H , Kim D H , Teng D , Kim J H , Kim W Y , Choi C H 
Published: January 2020

Abstract

Background
The aim of this study to assess the efficacy and safety of adalimumab (ADA), a monoclonal antibody against tumour necrosis factor α (TNF-α), and to explore predictors of response in Korean patients with ulcerative colitis (UC).

Methods
We conducted a prospective observational multicenter study over 56 weeks in adult patients with moderately to severely active UC. Clinical response and remission were assessed by Mayo score. Mucosal healing was defined as Mayo subscore 0 or 1. Faecal calprotectin (FC) were assessed at baseline, week 8 and 56. Adalimumab drug levels were checked at week 8 and at loss of response. Missing or incomplete data were handled using the nonresponder imputation method.

Results
A total of 146 patients were enrolled and included in the analysis. Clinical response rates were 52.1% (76/146) and 37.7% (55/146) at week 8 and 56, respectively. Clinical remission was achieved in 24.0% (35/146) and 21.9% (32/146) of patients at week 8 and 56. Steroid-free remission rates were 21.2% (31/146) at week 56. Mucosal healing rates were 39.0% (57/146) and 30.1% (44/146) at week 8 and 56. Prior use of anti-TNF-α did not affect the clinical and endoscopic responses. Treatment persistence was achieved in 57.5% (84/146) of patients at week 56. Adalimumab drug level was significantly higher in patients with clinical response (10.8 vs. 8.0, p = 0.004), clinical remission (11.7 vs. 8.8, p = 0.007) and mucosal healing (11.0 vs. 8.5, p = 0.010) at week 8. Adalimumab dose was escalated to 40 mg weekly in 25 (17.1%) patients, and clinical response and remission were achieved in 40% and 20% of patients at week 56, respectively. Mean faecal calprotectin levels were significantly more decreased in clinical responders compared with non-responders at week 8 (336.3 mg/kg vs. 628.8 mg/kg, p &lt; 0.001). The Fecal calprotectin levels are well correlated with endoscopic severity, and the best cut-off value to predict mucosal healing was 274 mg/kg. The lower endoscopic severity, higher body mass index and higher serum albumin level at baseline were associated with a clinical response at week 8. The lower Mayo score, lower C-reactive protein level, clinical response (74.5% vs. 38.5%, p &lt; 0.001) and mucosal healing (52.7% vs. 30.8%, p = 0.008) at week 8 were associated with clinical response at week 56. Serious adverse drug reactions were identified in 2.7% (4/146) of patients including 1 case of pulmonary tuberculosis.

Conclusion
Adalimumab is safe and effective for induction and maintenance in Korean patients with UC, regardless of prior anti-TNF therapy. Adalimumab drug level is associated with the efficacy of induction therapy. A better response to induction therapy can predict a better long-term response.
P498 Loss of response of anti-TNF in Crohn’s disease patients single-centre experience
Authors: Atanassova A , Georgieva A C , Mirchev M 
Published: January 2020

Abstract

Background
Despite the timely commencement of the biological treatment, only about 30% will respond to it, and about 1/3 will lose the initial anti-TNF (tumour necrosis factor) response.

Methods
We retrospectively studied the data of 69 Crohn’s disease (CD) patients who started biological treatment with anti-TNF-ADA/ IFX. We excluded patients who are primary nonresponders to IFX/ADA. In patients with induction of clinical response, we investigated and analysed the frequency of subsequent loss of response (LOR) to IFX/ADA. We analysed the possible risk factors that have led to LOR.

Results
Of the 69 patients undergoing biological treatment, 71.01% achieved a clinical response during the course of the follow-up. There is a correlation between the presence of a clinical response and the CD course- x2 = 10.78, p = 0.013, ρ = 0.241, (p = 0.046). Inflammatory phenotype (В1) manifestation among our patients is a factor for achieving a clinical response OR = 3.68 (1.116–11.73), p = 0.021, whereas the presence of a penetrating form is a risk factor for the lack of response OR = 6.13 (1.29–29.01), p = 0.019. The presence of intestinal complications is a risk factor for the lack of response- OR = 3.2 (1.61–6.37), p = 0.001. During the course of the follow-up in 30.61% of cases, we observed LOR (men/women - 86.66%/13.33%, p &lt; 0.05 (p = 0.02), in 60.00 % this was between 1–2 years, on average 20.62 ± 13.07 months from the start of the biological treatment. A total of 46.66% of patients required treatment with another anti-TNF drug due to secondary loss of response. A total of 50% of patients needed a reduction of the dose interval. Over 50.00% of those with LOR have an extensive disease (L3). A total of 40% have В1 and 33% have stricturing (В2) and penetrating (В3) phenotypic expression. In 26.66%, we observed progression of the disease range, and in 46.66% of patients - intestinal complications, none of whom had subsequent surgery. In 21.42% of LOR patients there is a combination of intestinal complications and progression according to disease localisation. 93.33% of CD patients with LOR have a persistence of extraintestinal manifestations (EIMs); those with two or three EIMs predominate. We discovered that gender was a risk factor for loss of response, OR = 8.36 (1.16–60.26), p = 0.005, as is the combination of В2 and В3 form of the disease OR = 14.72 (2.47–87.79), p = 0.003. Patients who lost response during the course of treatment had higher mean faecal calprotectin, CDAI and CRP prior to the initiation of the anti-TNF therapy.

Conclusion
The high activity of the disease measured with CDAI, faecal calprotectin and CRP, male gender, the combination of penetrating and stricturing form during the course of the disease are all risk factors for the loss of response.
P503 Changes in clinical use of vedolizumab are driven by lower drug costs and are associated with better outcomes: a real-life single-centre Spanish experience
Authors: Gonzalez Lama Y , Calvo M , Matallana V , Gonzalez-Partida I , Omella I , Vera M I 
Published: January 2020

Abstract

Background
Vedolizumab (VDZ) has shown efficacy in the treatment of inflammatory bowel disease (IBD). Available data show better outcomes in naïve patients than in AntiTNFa experienced patients, and current ECCO guidelines support first-line use of VDZ since 2017. Nevertheless, reimbursement of VDZ was initially approved in Spain only in patients failing to at least one AntiTNFa agent (except contraindication) until January 2018 when, following a significative decrease in costs of VDZ, reimbursement was approved also in naïve patients. Our aim was to elucidate if our clinical use of vedolizumab have evolved after costs decrease, and if was associated with better clinical outcomes.

Methods
Retrospective review of all VDZ treated patients with at least 6 months of follow-up in a referral IBD Unit of a tertiary centre in Madrid (Spain) since December 2014. Demographics, clinical data and information regarding VDZ treatment were collected.

Results
118 IBD patients included (61(52%) Crohn’s disease, 57(48%) ulcerative colitis): 62(53%) female; median age 48(IQR 32–63) years. 64 patients started VDZ before 2018, 54 since January 2018. Among patients who started VDZ treatment before and after January 2018: 9(14%) and 22(41%) respectively were naïve to antiTNFa (p = 0.001); 38(60%) and 10(18.5%) respectively had previously received at least 2 anti-TNFa agents (p = 0.0001). Among patients who started VDZ treatment before and after January 2018, 25(39%) and 6 (11%), respectively, had VDZ intensified along the follow-up (p = 0.001); 36(56%) and 12(22%) respectively withdrawn VDZ (p = 0.0001); 40(73%) and 15(27%) respectively withdrawn or intensified VDZ along the follow-up (p = 0.0001).

Conclusion
Lower costs have facilitated earlier use of VDZ in our clinical practice, towards increase use in patients who have failed to one single AntiTNFa agent or even naïve to AntiTNFa. This evolved a pattern of VDZ use is associated with better clinical outcomes in terms of VDZ intensification and/or withdrawn. Price policies facilitating appropriate access to drugs, such as VDZ, should be more easily and quickly acceptable by national health authorities. Patient-centred care demand best use of all available drugs, including VDZ.
P504 Remote cannabis-therapy management platform for IBD patients: performance assessment
Authors: Sweed G , Shapira C , Naftali T 
Published: January 2020

Abstract

Background
Efficient IBD symptomatic control, especially in severe patients, is still lacking while conventional management options agents carry risks for long-term side effects such as malignancy and infections. Only about 60% of IBD patients initially respond to conventional therapy thus, a growing number of IBD patients turn to use medical cannabis to relieve their symptoms. The large selection of cannabis varieties available in the markets, together with lack of evidence-based cannabis therapy guidelines, practically turns cannabis care to a self-medicating hit-or-miss treatment. Yet, despite its large therapeutic window, cannabis care still carries unknown risks of short-and long-term side effects and tolerance. SelfX is a novel cannabis-therapy management web platform, designed to monitor patients in various clinical conditions. It is a cloud-based decision-support physician tool, consisting of personal patient wearable monitoring device, mobile app and physician web portal.

Methods
SelfX capability to detect and alert of IBD patients in need of cannabis treatment protocol change consideration (including cessation of treatment), was examined in a proof of concept observational clinical study. Men and Women aged 18–65 (n = 26) with IBD who were already treated with cannabis prior to the study initiation, and held a valid cannabis license from the Israeli Ministry of Health, were recruited at Meir Medical Center in Israel and completed 6 weeks of remote monitoring. A designated statistical formula developed by our team for change-point detection was applied to alert of any negative clinical trends, including an increase in resting heart rate, decrease in sleep quality, increase in daily self-report IBD scoring system, adverse events and cannabis patterns use.

Results
The study achieved its primary objective to alert in real-time of detected change points which enabled an educated calibration of a personal adaptive alerts function. Study group post hoc analysis revealed significant and informative system performance: 60 objective negative trends alerts, and 27 subjective negative trends alerts were detected in real time.

Conclusion
Currently physicians require a practical tool to monitor short-and long-term safety and efficiency of cannabis use. Our work demonstrates the importance of continuous remote monitoring alongside laboratory routine measurements for IBD patients treated with cannabis. Future interventional studies will expand valuable monitored parameters scope range and will associate monitored data points with personal cannabis patterns use. SelfX platform offers a safety-net and an educated adaptive optimisation tool for continuous remote patients management in real time.
P511 Association of ustekinumab serum concentrations and clinical outcomes: results from the mUST-DECIDE trial
Authors: Bressler B , Sattin B , Williamson M A , Khanna R , Seow C H , Dajnowiec D , Karra K , Gao L L , Afif W 
Published: January 2020

Abstract

Background
Therapeutic drug monitoring is an important adjunct in optimising IBD management in patients treated with anti-TNF therapies. However, it remains unclear whether these principles apply to non-anti-TNF biologic therapies, such as the anti-IL12/23 agent, ustekinumab (UST). A follow-up analysis of the ‘mUST-DECIDE’ study explores the correlation between UST drug level and clinical outcomes.

Methods
111 consecutive UST-treated adult CD patients across 11 sites in Canada from April 2017 to January 2018 were evaluated. Clinical decisions were recorded for all subjects at the single study visit and blood was drawn for TDM (Sanquin, radioimmunoassay). A retrospective chart review was completed in patients who had a follow-up visit ≥ 30 days after the baseline visit. Improved disease control (primary outcome) was defined as a composite assessment outcome meeting ≥ 1 disease control criterion (symptomatic, endoscopic/imaging, biochemical) without any of the non-response criteria (inadequate or loss of response, worsening of any disease control criteria, initiation of any CD-related medications and adverse events). Serum [UST] were categorised as therapeutic, subtherapeutic or uninterpretable based on their position in a 2 compartment PK model [subjects on Q8W dosing were assessed as per the log-linear model which projected a therapeutic level of ≥4.5 µg/ml at 4 weeks and ≥1.0 µg/ml at 8 weeks].

Results
53 patients had a clinical follow-up visit and an interpretable serum [UST]. Patients had refractory disease (89% anti-TNF-exposed, median 16.4 years since diagnosis), but clinically well (66% had baseline HBI &lt;5) on treatment with UST for a median [IQR] of 16.5 [10.4–26.8] months. At baseline, the majority had serum [UST] in the therapeutic range (n = 44/53, 83%). After a median [IQR] of 148 [104–193] days, improved disease control was achieved by 51% of patients at next clinic visit. The outcome appeared independent of achieving therapeutic [UST] at baseline (OR[95% CI] = 0.80[0.19–3.38]). Dose-adjustment occurred in eight (15%) patients and improvements were observed in 75% of these patients. Subgroup analyses failed to detect clinical outcomes that were dependent on therapeutic serum [UST] (Table 1). No new safety signal was observed, no patient samples were positive for antibodies to UST.

Conclusion
The sub-study did not detect any association between routine serum [UST] and short-term clinical outcomes at the next patient visit. These data broadly suggests that the routine measurement of serum UST in CD patients does not aid in disease management, though further studies across different clinical scenarios (e.g. loss of response) are warranted.
P512 Efficacy of tofacitinib for the treatment of moderate-to-severe ulcerative colitis: real-world data
Authors: XIAO Y , Lakatos P L , Bourdages R , Bitton A , Afif W , Kohen R , Berberi M , Bessissow T 
Published: January 2020

Abstract

Background
A significant proportion of patients do not respond to therapy for moderate to severe ulcerative colitis (UC), including thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-a and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, data on its real-life efficacy remains sparse.

Methods
We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included the rate of biomarker normalisation, corticosteroids-free clinical remission and severe infections. We conducted a multi-centre retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalisation was defined as faecal calprotectin ≤250 μg/g. Severe infection was defined as an infection requiring hospitalisation.

Results
During the study period, 40 patients with UC were started on tofacitinib at 10 mg/kg twice a day. Amongst the patients, 85% (n = 34) had failed ≥1 biologic and 50% (n = 20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment; 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n = 34) and clinical remission occurred in 63.2%(n = 24). At 6 months, clinical response occurred in 73.3% of patients (n = 22) and clinical remission was sustained in 53.33% (n = 16). Biochemical normalisation occurred in 29.0% (n = 11) and 30.0% (n = 9) at 3 and 6 months respectively. Additionally, 63.2% (n = 24) of patients and 43.3% (n = 13) of patients achieved steroid-free clinical remission at 3 and 6 months respectively. In the interim, one patient developed a serious infection requiring discontinuation of the drug.

Conclusion
Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow-up.
P519 Higher anti-TNF α trough levels are not associated with increased radiological response in perianal fistulising Crohn’s disease: A multicentre study
Authors: LEE T , Gilbert L , Srinivasan A , Lee A , van Langenberg D , Martin C , Ding N , Sparrow M 
Published: January 2020

Abstract

Background
Perianal fistulas remain a debilitating and clinically challenging manifestation of Crohn’s disease (CD), given their prevalence and relative treatment resistance. Since the advent of biologic therapy, particularly the anti-TNFα agents infliximab and adalimumab, patient outcomes have improved. Serum trough levels have been associated with mucosal healing in luminal CD. However, the relationship between trough drug levels and healing of perianal fistulas remains less clear, with few studies assessing this cohort, and clinical healing typically defined as the primary endpoint. The aim of this study was to assess the relationship between radiological healing of perianal fistulising Crohn’s Disease (pfCD) on MRI, and serum trough drug levels, in patients treated with anti-TNFα therapy.

Methods
In this multi-centre, retrospective cross-sectional study, patients with pfCD who had trough levels measured within 6 months of a pelvic MRI were included. We collected patient demographics, infliximab and adalimumab trough levels, the presence or absence of anti-drug antibodies, concomitant steroid or antibiotic therapy, and Van Assche scores on MRI. The primary outcome, radiological response, was defined as a Van Assche score of 7 or less, while no response was defined as a score of greater than 7.

Results
A total of 99 patients were included (65 on infliximab, 34 on adalimumab). For patients receiving infliximab, the median drug levels for responders (n = 22) compared with non-responders (n = 43) were 5.5 mg/ml vs. 3.9 mg/ml respectively (p = 0.16). For patients receiving adalimumab, the median drug levels for responders (n = 14) compared with non-responders (n = 20) were 6.3 mg/ml vs. 3.1 mg/ml respectively (p = 0.09). On ROC curve analysis, the AUC for the association between radiological response and infliximab levels was 0.61, while for adalimumab it was 0.67. On quartile analysis, there appeared to be an increased response for increase in infliximab trough level quartile, with the exception of the highest quartile, however this association was not statistically significant (OR 1.36, 95% CI 0.85–2.16, p = 0.20). In comparison, the quartile analysis of adalimumab trough level and response demonstrated an exposure-response relationship (OR 2.24, 95% CI 1.11–4.52, p = 0.02).

Conclusion
Trough infliximab and adalimumab levels in patients who achieved radiological response were not significantly higher compared with those who did not, however quartiles analyses demonstrated trends toward an exposure-response relationship, in particular for adalimumab. The association between trough levels and radiological response could be further characterised with a larger, and ideally longitudinal, study.
P521 Infection of the anal canal by human papillomavirus in Crohn’s disease
Authors: Guzela V , Sobrado Júnior C , Nadal S , Nadal C R , Villa L L , Gonçalves A P , Boarini L R , Nahas S C , Cecconello I 
Published: January 2020

Abstract

Background
Compare the frequency of subclinical papillomavirus (HPV) in the anal canal os Crohn′s disease (DC) patients to a control group by smear cytology and polymerase chain reaction (PCR) and hybridisation and to assess whether there is correlation with the presence of immunosuppression and anal manifestations of the disease, besides establishing the agreement between the two diagnostic methods used.

Methods
Two groups were selected, one with DC and others to be the control population. All the individuals were submitted to smear cytology (two brushes inserted in sequence in the anal canal) and a third one preserved for molecular analysis (PCR and hybridisation). The cytology was classified according to Bethesda criteria as normal, atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL). The molecular analysis was considered with HPV present or absent and types 16 and high-risk HPV group identified.

Results
During sixteen months, 104 patients underwent anal cytology collection for smear preparation and HPV molecular method detection. The control group consisted of 41 individuals and the DC of 63 patients (32 immunocompetent and 31 immunosuppressed). ASCUS and LSIL represented respectively 26.8% and 22.0% of the control patients and 28.6% and 39.7% of the Crohn′s patients, with no statistically significant difference between the groups. HPV was identified in 17.1% of patients in the control group and 27% of patients with CD by the molecular method, being predominantly high risk in both groups. In a subanalysis considering Crohn’s disease patients with and without immunosuppression and the control group, there was no statistical difference between the frequencies detected by PCR and hybridisation (p = 0.084) as well as the anal manifestation of Crohn’s disease. The Kappa coefficient for agreement between smear anal cytology and HPV identification by PCR and hybridisation was -0.127 in the total sample.

Conclusion
In this study, is possible to conclude that in the sample studied there was no difference between subclinical HPV anal infection between control patients and Crohn’s disease group evaluated by both cytology and hybridisation and immunosuppression and anal impairment did not influence these results either. Anal cytology and hybridisation did not show agreement represented by the Kappa coefficient in this population.