bluuebunny/crossref_metadata_2025_split huggingface dataset:
P352 Infliximab-therapy intensification based on endoscopic activity suppresses treatment interruption among patients with Crohn’s disease
Authors: Komaki Y , Kanmura S , Yutsudo K , Kosuke K , Komaki F , Tanaka A , Nishimata N , Sameshima Y , Sasaki F , Ooi H , Tokushige K , Sameshima Y , Ido A 
Published: January 2020

Abstract

Background
Although biologics have improved the therapeutic goals for Crohn’s disease, the problem of diminishing efficacy exists. With recent advances, it is possible to administer double doses or shortening the dosing interval of infliximab (IFX); however, its effectiveness and right timing of strengthening remain unclear. In this study, we examined the treatment outcomes in patients with Crohn’s disease who received IFX-therapy intensification for the reduction of IFX effects at multiple centres.

Methods
Of the 243 patients with Crohn’s disease who were seen at our hospital and related facilities from July 2002 to July 2018, a total of 46 patients who could be observed for more than 1 year after IFX-therapy intensification for diminished effect of IFX were included in this study. The relationship between patient background and continuation of therapy intensification was retrospectively examined using logistic regression analysis. Furthermore, the relationship between therapy intensification and the treatment discontinuation rates for each of double doses and shortening the dosing interval was also evaluated.

Results
Of the 46 patients (30 men and 16 women), 67.4% (31 cases) were able to continue therapy intensification for 12 months. In univariate analysis of the relationship between patient background and continuation of therapy intensification, therapy intensification due to the remaining endoscopic findings contributed to the decrease in therapy intensification interruption rate. However, multivariate analysis did not reveal any significant contributing factors. Next, treatment discontinuation rates were compared between the group in which therapy intensification was performed due to the remaining endoscopic findings (n = 14) or clinical symptoms (abdominal pain, diarrhoea, and subjective general condition) (n = 32). The rate of treatment discontinuation 12 months after treatment strengthening was significantly lower in the therapy intensification group due to the remaining endoscopic findings than in that due to clinical symptoms (7.1% vs. 43.8%, p = 0.015). The rates of treatment discontinuation between the group of double doses (n = 34) and the group of shortening the dosing interval (n = 12) were also compared, but there was no significant difference after 6 or 12 months of treatment strengthening.

Conclusion
Treatment interruption would less likely occur among patients with Crohn’s disease receiving IFX if IFX-treatment intensification is triggered by the remaining endoscopic findings and not by clinical symptoms.
P356 Infectious events in patients with inflammatory bowel disease: The impact of immunomodulators and tumour necrosis factor antagonist therapy
Authors: Andersson P , Karling P 
Published: January 2020

Abstract

Background
Immunomodulators (IM) and tumour necrosis factor antagonist therapy (anti-TNF) are effective treatments for inflammatory bowel disease (IBD) but has been associated with an increased risk for infectious diseases. We investigated the frequency of infectious events in patients with IBD and the association of infectious events with concomitant treatment with IM and anti-TNF therapy.

Methods
We performed a retrospective medical chart review of patients with IBD, 18 to 65 years of age, included in the Swedish Registry of IBD (SWIBREG) and treated in the catchment area of Umeå University Hospital, Sweden. Data were collected from the period January 1, 2006, to January 31, 2019. An infectious event was defined as an outpatient prescription of antimicrobials or a positive diagnostic test for infection.

Results
Among the 593 included patients (397 patients with UC and 195 patients with CD), 1398 events occurred. The proportion of events that occurred on treatment with corticosteroids, IM, anti-TNF, combination therapy (IM + anti-TNF) and without any immunosuppressive treatments was 8.3%, 35.8%, 17.7%, 10.0% and 47.4%. Of all patients, 60.4% had at least one infectious event, and 29.3% had &gt;0.3 events per year. Compared with patients not receiving immunosuppressive therapy, an event rate of &gt;0.3 per year was more common among those receiving immunomodulator monotherapy or combination therapy (Table), and was more common in patients with Crohn’s disease than ulcerative colitis (35.0% vs. 26.1%, p = 0.022). There were no significant differences in infectious events between patients who had received immunomodulator monotherapy and patients who had received combination therapy.

Conclusion
We found an increased frequency of infection associated with the use of combination therapy and immunomodulator monotherapy, but no difference between the two treatments.
P357 Importance of stool drug monitoring in anti-TNF-treated patients
Authors: Bacsur P , Szántó K , Madácsy T , Kata D , Ferenci T , Rutka M , Bálint A , Bor R , Fábián A , Milassin Á , Elekes G , Szepes Z , Nagy F , Földesi I , Maléth J , Farkas K , Molnár T 
Published: January 2020

Abstract

Background
Anti-tumour necrosis factor (TNF) therapy has dramatically changed the treatment of inflammatory bowel disease (IBD). The relationship between clinical outcomes and serum anti-TNF levels is controversial. This study aimed to perform simultaneous analyses of the serum, mucosal and faecal infliximab and adalimumab levels to determine the mucosal expression of TNF-α and assess the relationship of the anti-TNF-α levels in these biological samples with the endoscopic and clinical activities and body composition in IBD patients.

Methods
Consecutive IBD patients who received maintenance anti-TNF-α therapy and underwent colonoscopy were enrolled. We assessed the clinical disease activity, collected the blood, faecal and biopsy samples. The number of TNF-α positive cells in the mucosa was detected using immunofluorescent labelling. Serum, mucosal and faecal anti-TNF-α levels, anti-drug antibody level in the serum and faecal calprotectin were determined using ELISA. Each patient underwent body composition analysis.

Results
Fifty consecutive patients have been analysed in the study. The number TNF-α positive cells was significantly higher in the inflamed than in the un-inflamed part of the colon (p = 0.01); however, such a difference was not detected in case of tissue drug levels. Tissue drug level did not correlate with the serum drug level. Nevertheless, tissue drug levels of the samples obtained from the un-inflamed part of the colon were significantly higher in patients who were in remission (p = 0.03467). The presence of the drug in the faeces was significantly different according to disease activity (p = 0.0022). Drug levels in the biological samples did not show any association with the presence of anti-drug antibodies. Body composition parameters had no significant impact on the serum and tissue drug levels. Faecal calprotectin showed significant correlation with faecal drug concentration (p = 0.0162) and clinical and endoscopic activity (p &lt; 0.001).

Conclusion
To the best our knowledge, this is the first study to measure drug concentrations in all the relevant biological samples. Our findings highlight the importance of faecal drug monitoring because active disease may be present in spite of normal serum anti-TNF levels. Simultaneous determination of faecal drug concentration and faecal calprotectin may be more accurate for evaluating therapeutic responses in the future.
P360 Safety and clinical efficacy of double switch from originator infliximab to biosimilars CT-P13 and SB2 in patients with inflammatory bowel diseases (SCESICS): A multicentre study
Authors: Mazza S , Fascì A , Casini V , Ricci C , Munari F , Pirola L , Girelli C , Lupinacci G , Pastorelli L , Cavallaro F , Piazza O’Sed N , Ferraris L , Colucci A , Amato A , Maurizio V , Fiorino G , Caprioli F 
Published: January 2020

Abstract

Background
Since infliximab (IFX) patent expiry in 2015, several IFX biosimilars have been licensed in EU for all indications, including inflammatory bowel diseases (IBD). IFX biosimilars currently available in Italy include CT-P13 and SB2, both of which demonstrated comparable efficacy, safety and immunogenicity with IFX originator in IBD patients. Safety and clinical efficacy of single switch from originator IFX to CT-P13 have also been confirmed in a prospective clinical trial. On the contrary, data regarding multiple therapeutic switching of IFX originator with CT-P13 and SB2 are currently lacking.

Methods
This study was aimed to evaluate the safety and efficacy of double switch from IFX originator to CT-P13 and subsequently to SB2 in patients with IBD. From November 2018 to May 2019, patients undergoing IFX double switch in 8 Centres in Lombardy were retrospectively analysed. The overall rate of IFX discontinuation, incidence and type of adverse events (AE) and proportion of patients on clinical remission over time were recorded. Data were compared with a control group of 66 IBD patients single switched from IFX originator to CT-P13.

Results
Fifty-two double-switched IBD patients were enrolled (63% M, mean age 41 years, 75% Crohn’s disease, 25% ulcerative colitis). Main indications for IFX therapy were moderate to severe disease (50%) and steroid-dependent disease (25%). The overall 24- and 48-week IFX discontinuation rates following second switch (CTP13-&gt;SB2) were 2% (95% CI 0–6%) and 14% (95% CI 3–25%), respectively. During a median follow-up of 40 weeks (18–48), 4 patients (12%) experienced a total of 6 AE (2 cutaneous, 2 infectious, 1 articular and 1 immunological), leading to IFX discontinuation in 3 cases (6%). No infusion reactions were observed. At week 24 following second switch, 49 (94%) patients were in clinical remission, the remaining 3 patients not being in remission already at the time of second switch. Only one patient lost response after week 24, 48 (92%) of patients being in clinical remission at the end of follow-up. No differences in IFX discontinuation, AE and clinical remission rates were found between double-switched and single-switched patients. No clinical parameters were found to predict safety and efficacy outcomes.

Conclusion
The study supports both safety and efficacy of the double switch from IFX originator to CT-P13 and SB2 in patients with IBD, and demonstrates its non-inferiority to a single switch strategy, with potential cost implications.
P372 Effects of filgotinib on anaemia, thrombocytopenia and leukopenia: Phase 3 study results in patients with active rheumatoid arthritis and prior inadequate response/intolerance to biological DMARDs
Authors: Besuyen R , Genovese M , de Vlam K , Gottenberg J E , Kalunian K , Bartok B , Tan Y , Guo Y , Tasset C , Sundy J , Walker D , Takeuchi T 
Published: January 2020

Abstract

Background
Anaemia, thrombocytopenia and leukopenia in rheumatoid arthritis (RA) patients treated with non-Janus Kinase 1 (JAK1) selective inhibitors may be due to inhibition of haematopoietic growth factors signalling through JAK2. Therefore, we investigated anaemia, thrombocytopenia and leukopenia in patients with active RA with prior inadequate response/intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARDs) treated with filgotinib (FIL), a selective JAK1 inhibitor (FINCH-2; NCT02873936).

Methods
In the randomised, double-blind, placebo-controlled Phase 3 FINCH-2 trial, patients were randomised 1:1:1 to oral FIL 200 mg, 100 mg, or placebo (PBO) once daily plus conventional synthetic DMARDs for 24 weeks. In this subgroup analysis, we assessed shifts from baseline (BL) in haemoglobin (hgb), platelets (plt), neutrophils and lymphocytes.

Results
A total of 448 patients were treated; FIL 200 mg, n = 147; FIL 100 mg, n = 153; PBO, n = 148. Hgb, plt, lymphocyte and neutrophil counts remained consistent throughout the study. At BL, 28.8%, 0.9%, 2.2% and 5.8% patients had mild–moderate low hgb, plt, neutrophil and lymphocyte, respectively, and 1.1% had severely low lymphocyte levels. Of patients with mild–moderate hgb levels at BL, 13.1% with FIL 200 mg, 9.5% FIL 100 mg, and 7.6% PBO achieved normal hgb at Week 24, respectively (Table). Of those with normal BL hgb, only 6–9.8% had mild low levels at Week 24. Patients with BL mild-moderate low plts and neutrophils had normal levels at Week 24, except one with mild neutropenia on FIL 100 mg. Of patients with normal plt and neutrophil levels at BL, &gt;94% maintained these at Week 24 in all treatment groups. By Week 24, 3.2%, 5.2% and 2.2% of patients treated with FIL 200 mg, FIL 100 mg and PBO, respectively, in the mild–moderate subgroup and 1.7% in the severe subgroup treated with FIL 100 mg had normal lymphocyte counts.

Conclusion
In this subgroup analysis, most patients with normal hgb, plt, lymphocyte and neutrophil at BL maintained them over 24 weeks of FIL treatment. Of the patients with mild–moderately low hgb at BL, &gt;9% shifted towards normalisation. Similar patterns of improvement were observed for plt, lymphocyte and neutrophil counts. These results suggest that FIL does not increase the incidence of anaemia, thrombocytopenia or leukopenia in patients who entered the study with active RA despite prior bDMARDs.
P373 Telemedicine and inflammatory bowel disease: Results of the IBD assistant pilot project
Authors: Malickova K , Pesinova V , Bortlik M , Duricova D , Machkova N , Hruba V , Lukas M , Mitrova K , Vasatko M , Kostrejova M , Kolar M , Lukas M 
Published: January 2020

Abstract

Background
Telemedicine enables proper and immediate monitoring of the patient’s current health state, followed by well-timed and customised treatment. The aim of our study was to assess feasibility and safety of telemonitoring in Czech patients with inflammatory bowel disease (IBD). Furthermore, we wanted to evaluate the impact of telemonitoring on the number of outpatient′s visits and direct health-care cost.

Methods
We performed randomised controlled study including patients with IBD in stable remission on conventional therapy who were randomised either to telemonitoring (IBDA) or control (CTRL) group and were followed-up for 12 months. All IBDA patients had access to a specific web application which contained a set of questioners assessing disease activity and complications which were filled-in at least every 3 months. Evaluation of clinical activity was accompanied by measurement of faecal calprotectin (FC) at home using CalproSmart test. Individuals in the CTRL group were followed under the standard conditions as other outpatients.

Results
A total of 131 were included (42% males; 47% with Crohn′s disease) and randomised to IBDA (n = 94) or control group (n = 37). HBI/pMayo activity indexes were not significantly different at baseline (p = 0.636 and p = 0.853) and end of study (p = 0.517 and p = 0.890) in the two groups. Similarly, no significant difference in inflammatory markers (C-reactive protein, FC) was observed in either group (p&gt;0.05). The occurrence of intercurrent infections (0.93 vs. 0.81 cases of infection/patient-year, p = 0.87) or the need for hospitalisations (1 vs. 0) was similar between the groups. The number of outpatient visits was significantly lower in the IBDA than in the CTRL group (median number in IBDA group 0, in the CTRL group 4.2 visits, respectively, p &lt; 0.0001). Telemedicine led to a reduction in the direct annual health-care cost of patient follow-up by ~25% compared with the standard care.

Conclusion
Results of the first Czech IBD telemedicine study confirm the effectiveness and safety of the telemedicine approach, which led to a reduction in outpatient visits and savings in health-care costs while maintaining a high standard of health care.
Acknowledgements: Supported by the IBD-Comfort Endowment Fund.
P378 Mucosal healing is achieved in most of the inflammatory bowel disease patients in clinical remission with vedolizumab: a real-life single-centre experience
Authors: Calvo Moya M I , Omella Usieto I , Vera Mendoza M I , Matallana Royo V , Gonzalez Partida I , Manso Manrique M , Menchén Viso B , De Lucas Téllez de Meneses R , González Rodriguez M , Bella del Castillo P , González Lama Y 
Published: January 2020

Abstract

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

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

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

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

Abstract

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

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

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

Conclusion
Consistent with the findings of other studies, there are no differences in the pharmacokinetic characteristics or in the responses of patients depending on the dose of azathioprine. The use of a lower dose of AZA can provide a better tolerance of the drug, a better safety profile, and lower economic cost.