bluuebunny/crossref_metadata_2025_split huggingface dataset:
P012 Successful Use of Combination Biologic Therapy in Medically Refractory Pediatric Crohn's Disease and Sacroiliitis
Authors: Bass Julie , Goyal Alka 
Published: December 2019

CASE:
We present a patient with medically refractory Crohn’s disease, sacroiliitis and growth failure who showed remarkable response to combination therapy using two different biological agents along with an immunomodulator and no significant adverse events. A 14-year old male presented for 2nd opinion regarding management of refractory ileocolonic Crohn’s disease. He was diagnosed with Crohn’s disease at an outside center at 9 years of age. Initial treatment with systemic steroids and azathioprine was unsuccessful. He had sub-optimal clinical improvement on anti-tumor necrosis factor (TNF) therapy that included infliximab for 1 year, followed by adalimumab for 1.5 years. He subsequently struggled with repeated episodes of Clostridium difficile (CDI) requiring prolonged vancomycin taper. His therapy was then switched to vedolizumab, systemic steroids and azathioprine which provided some symptomatic relief, but he was noted to be persistently anemic with elevated inflammatory markers and poor growth. At the time of presentation to our center he was steroid dependent on prednisone 5 mg daily for 6 months while still on vedolizumab and azathioprine. He had mildly active clinical disease but severe growth failure and was negative for CDI. Repeat disease assessment noted severe granulomatous colitis and terminal ileitis with worsening disease in the distal colon. He was treated with Budesonide MMX and mesalamine enemas with no improvement. Vedolizumab levels were noted to be low and therefore therapy escalated to every 4-week intervals. Azathioprine was stopped due to lack of efficacy despite adequate levels. Due to body mass index (BMI) z-score of -2.4, exclusive enteral therapy was implemented for 3 months followed by transition to regular diet. His weight improved but there was no change in clinical activity or laboratory abnormalities. He subsequently developed leg and hip pain. Rheumatology evaluation was pursued, and he was diagnosed with sacroiliitis based on physical examination and a lumbosacral MRI. At this point a decision was made to use combination of two biologicals due to prior history of GI disease refractory to anti-TNF therapy. Adalimumab and oral methotrexate were given in addition to vedolizumab. He has been on this combination for last 9 months with no adverse events. Patient has shown excellent clinical response with normalization of inflammatory markers and resolution of anemia. His BMI z-score improved to 0.76 with weight gain of 25 kilograms in the past year. Combination biologicals are rarely utilized due to concerns for side effects and high cost making it difficult to obtain insurance approval. When used judiciously in patients with medically refractory disease it can be safe and effective. A paucity of literature exists regarding the use of combination biologicals especially in children.
P013 Characteristics of Fecal Microbiota Transplantation Use in Inflammatory Bowel Disease cohort
Authors: Bauer Christina , Long Millie , Zhang Xian , Sandler Robert 
Published: December 2019

BACKGROUND:
There is a growing interest in the role of gut bacteria in a variety of diseases and an emerging hypothesis that inflammatory bowel disease (IBD) is triggered by microbial dysbiosis in genetically susceptible individuals. Currently fecal microbiota transplantation (FMT) is utilized for the treatment of C. difficile colitis. Data on the efficacy of FMT for IBD are mixed, but patients are interested in its use for treatment of IBD. We sought to describe the use of FMT (self or medical professional administered) in individuals with IBD using IBD Partners, an internet-based cohort.

METHODS:
A total of 3,247 patients enrolled in the IBD Partners cohort were offered the opportunity to complete an optional survey on use of FMT. Bivariate statistics were used to determine factors associated with use of FMT including IBD disease characteristics, indication for FMT, and mode of FMT delivery.

RESULTS:
Of the 3,247 patients eligible to complete the FMT survey, 51 (1.6%) people responded that they had an FMT in the past. Of patients undergoing FMT, 22 patients had the FMT for C. difficile while 29 reported that the FMT was for another indication. Most patients receiving FMT for an indication other than C. difficile had UC/IC (25, 86.2%). Colonoscopy (68.2%) and nasogastric tube (18.2%) were the most common routes of administration for patients receiving FMT for C. difficile colitis. Self-administration (72.4%) and enemas (17.2%) were the most common routes of administration in patients receiving FMT for an alternate indication. Patients reporting FMT for an indication other than C. difficile were less likely to have a physician directing their FMT treatment (20.6%) as compared to patients receiving FMT for C. difficile (86.3%). Patient reported efficacy was lower for FMT given for a non-C. difficile indication.

CONCLUSION(S):
Patients undergoing FMT for an indication other than C. difficile infection were more likely to have UC, self-administer FMT, and were less likely to be receiving FMT under the guidance of a medical professional. FMT was not as effective for symptoms when given for a non-C. difficile indication. Patients should be counseled on potential harms and lack of efficacy data associated with FMT for IBD indications to try to discourage self-administered FMT without proper medical oversite.
P022 Factors Associated With Proximal Disease Extension in Ulcerative Proctitis: Experience From an IBD Tertiary Center in Southeastern Brazil
Authors: Ferreira Sandro , Parra Rogerio , Feitosa Marley , de Mendonça Rafaella , Borges Ingrid , Aprile Lílian , Cardoso Pedro , Féres Omar , José Joaquim Rocha , Troncon Luiz Ernesto 
Published: December 2019

BACKGROUND:
Ulcerative proctitis (UP) accounts for a significant proportion of cases of ulcerative colitis (UC) and implies limited involvement of the rectum. Some patients presenting initially with UP may progress to more extensive colitis (inflammation found distally to the rectum-sigmoid junction). Although several predictive factors for this progression have been described, none has been established as definitive. We aimed at determining risk factors predictive of proximal disease extension in UP.

METHODS:
Retrospective analysis of data from 97 patients (67% female) with UP (Montreal Classification: E1) with at least 12 months of follow-up at the local University Hospital from January 2001 up to December 2018. Proximal extension was evaluated endoscopically during follow-up and was defined as E1 progressing to E2/E3. Factors examined comprised age, gender, race, presence of extraintestinal manifestations, Mayo endoscopic score, disease relapse, use of corticosteroids, immunosuppressive and biological agents and colectomy. We used univariate analysis (Chi-square test) to assess the association of individual factors to proximal disease extension.

RESULTS:
A total of 29 (29.9%) patients experienced proximal disease extension during a mean follow-up of 137.36 ± 86.63 months. The following factors were significantly associated with proximal disease extension: higher initial Mayo score (P = 0.035) and higher initial disease severity (P = 0.0024). Use of corticosteroids initially (86.2% vs 41.2%, P < 0.0001), increased disease relapse rate (86.2% vs 20.6%, P < 0.0001) and the need for immunosuppressive agents (57.1% vs 13.6%, P < 0.0001) or biological agents (42.9% vs 10.3%, P < 0.0001) were all significantly higher among UP patients with disease proximal extension, when compared to non-extensors. Colectomy was also associated with proximal disease extension (P = 0.0002). No significant association was found between UP proximal extension and gender, race, age at diagnosis and extraintestinal manifestations.

CONCLUSION(S):
UP is a dynamic disease that may progress over time. UP patients with increased clinical and endoscopic severity at the diagnosis are likely to evolve with proximal extension and should be more carefully followed up.
P024 Clinical Aspects and Associated Factors With Surgical Resection in Crohn's Disease Patients
Authors: Ferreira Sandro , Xavier Luana Dias , Borges Ingrid , de Mendonça Rafaella , Lemos Priscila , Aprile Lílian , Parra Rogerio , Feitosa Marley , Féres Omar , Rocha José Joaquim , Troncon Luiz Ernesto 
Published: December 2019

BACKGROUND:
Despite the numerous advances in medical treatment, it is estimated that a significant percentage of patients with Crohn's disease (CD) requires bowel resection at least once. The aim of this study was to evaluate patient characteristics and factors associated to surgical resection in patients with Crohn's disease in a tertiary IBD unit in Southeastern Brazil.

METHODS:
Retrospective analysis of data from 247 patients with Crohn's disease in follow-up at the University Hospital, Ribeirão Preto Medical School, from January 2000 up to December 2016. Medical records data comprised age, gender, disease location, disease behavior, disease duration and smoking. Patients were divided into two groups: presence or absence of surgical resection.

RESULTS:
Out of the 247 patients with CD, 111 underwent surgical resection (53.2% female, 82.9% Caucasians, mean age: 45.49 ± 13.30 years). More than one surgical procedure was performed in 15.3% of patients. Main indications for surgery were: stenosis (10.3%), clinical intractability (6.5%) and massive hemorrhage (2.7%). Smoking (P = 0.0109, OR = 2.244; 95% CI: 1.237 to 4.056), stenotic phenotype (P < 0.0001, OR = 5.294; 95% CI: 3.073 to 9.1212), ileo-colonic location (P < 0.0001, OR = 3.447; 95% CI: 2.061 to 5.698), longer disease duration (P < 0.0001) and more advanced age (P = 0.001) were significantly associated with operations for CD. No significant differences were observed in relation to gender, race, age at diagnosis and previous use of corticosteroids.

CONCLUSION(S):
Need for surgical treatment is still frequent in patients with CD. Smoking (current or past), longer disease time, stenotic phenotype and ileo-colonic localization in CD patients were associated with a higher risk of surgery in our IBD Unit. Awareness about factors associated with unfavorable outcome allows these patients to be treated more appropriately.
P026 Investigating Predictors of Antibodies to Infliximab Formation in Inflammatory Bowel Disease – The Importance of Immunomodulators
Authors: Freitas Marta , Magalhaes Rui , Dias de Castro Francisca , Moreira Maria João , Cotter José 
Published: December 2019

BACKGROUND:
Anti-tumor necrosis factor (TNF)-α have revolutionized the treatment of inflammatory bowel diseases (IBD), modifying their natural history. Loss of response to anti-TNFs is a clinical challenge and has been associated with formation of antibodies.

AIM:
To identify predictive factors of antibodies to infliximab (ATI) formation in IBD patients.

METHODS:
Retrospective single-center study including all consecutive IBD patients being treated with infliximab with at least one ATI and infliximab level determination and with a minimum follow-up of six months after the first testing. Presence of ATI was considered if at least one determination was positive during the follow-up and infliximab levels at this testing were registered. Clinical and demographic data obtained included disease phenotype, surgical background, duration of infliximab therapy, use of premedication, concomitant immunomodulator therapy at the time of testing, compliance, occurrence of an infusion reaction and biochemical assessment at the time of first induction treatment.

RESULTS:
104 patients were included, 56 females (53.8%) with mean age of 38.2 ± 13.1 years. The overall prevalence of detectable ATI was 28.8% (30) and the mean time to its formation was 32.8 ± 24.3 months. Most (66.7%) patients with ATI had simultaneously nontherapeutic levels of infliximab. Patients treated with concomitant immunomodulators were less likely to develop ATI (33% versus 88%, P < 0.001). Additionally, it was found that patients with Ulcerative Colitis (UC) were more likely to have detectable ATI than those with Crohn Disease (CD) (44.4% vs 23.4%, P = 0.04). However, UC patients were less treated with concomitant immunomodulators (48.1% vs 80.5%, P = 0.001). At logistic regression analysis only lack of immunomodulator use (P < 0.001; OR 13.5, CI 95%, 4.63–40.0) was independently associated with ATI formation.

CONCLUSION(S):
Concomitant immunomodulator therapy was the only protective factor for the ATI formation, supporting its institution to prevent loss of response to anti-TNFs.
P038 Comparing the Efficacy and Safety of Subcutaneous Vedolizumab Versus Adalimumab for the Treatment of Ulcerative Colitis: A Network Meta-Analysis
Authors: Jairath Vipul , Chan Keith , Lasch Karen , Keeping Sam , Agboton Christian , Blake Aimee , Jansen Jeroen , Patel Haridarshan 
Published: December 2019

BACKGROUND:
Vedolizumab (VDZ), a gut-selective monoclonal α4β7 integrin antibody, is approved for the treatment of moderately to severely active ulcerative colitis (UC) and Crohn’s disease. Intravenous (IV) VDZ was recently shown to be superior to subcutaneous (SC) adalimumab (ADA) in VARSITY (1), the first head-to-head randomized controlled trial (RCT) of biological therapies in UC. No comparative efficacy or safety data versus ADA exist for VDZ SC, a new formulation in development (2). To generate estimates of the comparative efficacy and safety of VDZ SC versus ADA, we conducted a network meta-analysis (NMA) of RCTs.

METHODS:
The NMA was conducted using results from a targeted literature review that identified RCTs of both VDZ and ADA: GEMINI 1, VISIBLE 1, ULTRA-2, and VARSITY. In the former two trials, responders were rerandomized at the end of induction, whilst the latter two trials were treat-through designs. To adequately analyze these trials in one network of evidence, efficacy outcomes were assessed conditionally upon response at start of maintenance. For treat-through studies, this was response at 6/8 weeks. Efficacy outcomes in the maintenance period were response and remission at 52/54 weeks. Safety outcomes were overall adverse events (AEs), serious AEs (SAEs), overall infections, serious infections, and AEs leading to discontinuation as reported at 52 weeks. Odds ratios (OR) with 95% credible intervals (CrI) were estimated using probit and binomial NMA models. ADA SC 40 mg Q2W, VDZ IV 300 mg Q4W, and VDZ IV 300 mg Q8W were all compared against VDZ SC 108 mg Q2W (reference group).

RESULTS:
ADA had lower rates for maintenance of response and remission relative to VDZ SC, but this was not statistically significant (ORs with 95% Crl: 0.60 [0.33, 1.08] and 0.59 [0.33, 1.09], respectively). Although overall AEs were significantly higher with ADA compared with VDZ SC (OR 2.02 [1.04, 3.89]), other safety outcomes were similar: overall infections, OR 1.86 (0.94, 3.77); serious AEs, OR 1.41 (0.54, 3.75); serious infections, OR 0.39 (0.05, 2.73); AEs leading to discontinuation, OR 2.58 (0.80, 9.44). As expected, VDZ IV had similar maintenance efficacy and safety outcomes relative to VDZ SC.

CONCLUSION(S):
Results from this indirect treatment comparison suggest that VDZ SC may achieve higher rates of maintenance response and remission among responders at start of maintenance than ADA and is associated with a lower risk of overall AEs. In the absence of a head-to-head trial between VDZ SC and ADA SC, these findings support a favorable benefit-risk profile of VDZ SC in UC.
P043 Response Loss When Transferring Patients With Inflammatory Bowel Disease From the Original Drug Infliximab to Its Biosimilar
Authors: Knyazev Oleg , Kagramanova Anna , Shkurko Tatyana , Lishchinskaya Albina , Kulakov Dmitriy , Zvyaglova Mariya , Parfenov Asfold 
Published: December 2019

BACKGROUND:
Biosimilars are analogues of biopharmaceutical drugs, with a close but not identical original molecule. They are modern drugs based on proteins obtained by biological synthesis in yeast and bacteria cells. Biosimilars offer greater access to affordable treatment for inflammatory bowel diseases, and they are comparable in efficacy and safety to the original drugs.

OBJECTIVE:
To identify the frequency of response loss in patients with inflammatory bowel disease (IBD) receiving biosimilar infliximab during the year of observation.

METHODS:
In the Department of inflammatory bowel diseases of the Moscow scientific center named after A. S. Loginov of the Department of Health of Moscow, 60 patients with IBD were observed, who were transferred from the original drug infliximab (IFX) to the introduction of biosimilar infliximab, were divided into two groups. Group 1 (n = 30) patients did not receive the anti-TNF-α drug and received the original IFX drug, and were then transferred to biosimilar IFX. The 2nd group of patients (n = 30) had previous experience of receiving anti-TNF-α before the introduction of IFX and then it’s biosimilar. The loss of response in the transfer of patients with IBD from the original drug infliximab to its biosimilar was assessed according to clinical, laboratory and instrumental data. The comparative analysis was carried out by the method of four-field tables using nonparametric statistical criteria.

RESULTS:
During the year of observation among patients were did not receive the anti-TNF-α drug IBD patients receiving the original when translating IFX on the IFX biosimilar the loss of response occurred in 5 cases (16.7%) patients. In most cases, the loss of response to biosimilar (13 (43, %)) developed if IFX and its biosimilar were not the first anti-TNF-α drugs (OR - 0.385; 95% CI 0.157–0.945; x2 - 5.079; P = 0.02857).

CONCLUSION(S):
The rate of response loss when transferring patients with inflammatory bowel disease from the original drug infliximab to its biosimilar is significantly higher in patients with IBD, if IFX and its biosimilar were not the first anti-TNF-α drugs.
P054 Phenotypic and Genotypic Characterization of VEOIBD: Experience From a Single-Centre in Brazil
Authors: Santana Vianna Marina , Vieira Antunes Karina de Almeida , Barbosa dos Santos Paloma Estefanne , Seoane Marcela S , Lindoso Livia , Toma Ricardo , Deboni Mariana 
Published: December 2019

BACKGROUND:
Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract, due to inadequate interaction between immune and environmental factors in a genetic susceptible host. When the age of onset is below the age of 6 years, it is called very early onset IBD (VEO-IBD). VEO-IBD is a heterogeneous disorder clinically characterized by severe and often refractory intestinal inflammation. The goal of this study was to characterize the profile of patients with very early onset inflammatory bowel disease in a single-center in Brazil.

METHODS:
We performed a retrospective study using data from an IBD outpatient clinic between January 2016 and April 2018. The patients' demographic, clinical and laboratory features were assessed by retrieval of data from medical records. The diagnosis of IBD and its phenotypes were defined according to the Paris classification.

RESULTS:
Of the 140 patients with IBD, 36 (25.7%) were diagnosed with VEO-IBD, 50% were male. Ulcerative colitis (UC) was diagnosed in 52.9%, Crohn's disease (CD) in 41.2% and indeterminate colitis in 5.9%. The mean age at onset of symptoms was 1 year and 8 months and diagnosis at 2 years and 9 months, with an average interval for diagnosis of 11 months. The average follow-up was 7.3 years (11 months to 15 years and 6 months). Family history of autoimmunity was present in 14.7%. At diagnosis, bloody diarrhea was the main symptom (67.6%), followed by abdominal pain, fever, and weight loss. Fistulizing disease was present in 8.8% of patients and anemia in 55.8%. At follow-up, sclerosing cholangitis was the main extraintestinal manifestation presented (20.6%), followed by rheumatologic manifestations (14.7%) and severe anemia requiring blood transfusion (14.7%). Immunobiological use and/or combination therapy was indicated in 41.2% of patients and 67.6% achieved mucosal healing. 27.5% patient had low weight gain despite nutritional support and 11.8% needed intestinal resection. Twelve patients had the genetic diagnosis of VEO-IBD (XIAP (2), LRBA, DGC (3), PKI3 (2), IL10R, STAT1, ATGI6L1, RIPK1) and underwent specific treatment.

CONCLUSION:
Children presenting with VEO-IBD, especially those with unusual manifestation require immune and genetic evaluation to rule syndromes that may need an alternative treatment affecting long-term prognosis. Increasing awareness of monogenic disorders affecting the intestinal immune homeostasis can help diagnose VEO-IBD, guide target therapies and prevent disease complication.
P058 Online Feedback: Perceptions About Family Planning in Men and Women With IBD in Brazil
Authors: Lima Fernanda , Machado Marta 
Published: December 2019

BACKGROUND:
Inflammatory Bowel Disease (IBD) predominantly affects young and reproductive age patients. Fears that IBD itself and/or its medication may inadvertently affect stroke, pregnancy outcome and lactation safety are a significant concern for IBD patients. Myths and lack of proper education can make patients voluntarily choose not to have children, stop treatment during pregnancy and refuse lactation. The voluntary lack of children and the constitution of smaller families has been observed and reported in IBD. There is a lack of studies on the perceptions of patients in this scenario in Brazil. The objectives were to evaluate what are the perceptions about family planning in men and women with inflammatory bowel disease.

METHODS:
This prospective study was conducted by a self-completed cross-sectional online questionnaire answered by 951 female and male IBD patients over 18 years of age throughout Brazil in 2019 for 10 weeks.

RESULTS:
A total of 951 patients answered the questionnaire, 80% (761) of the questionnaires were usable. The respondent population was 76.34% female, of these 76.38% aged between 18 and 38 years, 57.29% were diagnosed with Crohn's disease, 38.54% ulcerative colitis and 4.17% colitis. undetermined. Regarding the male data, a total of 23.66% of the sample, 78.2% were between 18 and 38 years old; 69.67% were diagnosed with Crohn's disease, 27.96% ulcerative colitis and 2.37% indeterminate colitis. In both genders, female and male consecutively, 49.14/42.48% were using contraception, 41.75/50.24% had children, 50.39 / 33.02% did not plan pregnancy, 58, 10/47.57 had only one child, 30.77/28.78%, the disease disrupted family planning, 67.08/70.37% did not consider having more children, 73.22/87.56% reported that their doctors never addressed family planning during treatment and 43.73/13.81% proactively approached the issue with their doctors.

CONCLUSION(S):
It can be seen from the data presented that the theme of family planning is little explored by both doctors and patients, and that inflammatory bowel disease can influence family planning with regard to not having children or considering having more children.