bluuebunny/crossref_metadata_2025 huggingface dataset:
P016 Lipidomics in ulcerative colitis reveal disruption of mucosal lipid composition associated with the disease state
Authors: Joseph Diab , Rasmus Goll , Terkel Hansen , Einar Jensen , Thomas Moritz , Jon Florholmen , Guro Forsdahl
Published: July 2019

BACKGROUND:

Several genetic, bacterial, and environmental factors appear to lead to the onset of ulcerative colitis (UC). Moreover, UC seems to be associated with alterations in lipid metabolism, and a disruption of the balance between pro and anti-inflammatory molecules. Membrane bioactive lipids modulate the immune response by functioning as intra- and intercellular signaling molecules. However, there are only few studies describing the mucosal lipid bio-signatures during IBD. Therefore, our study aims to characterize mucosal lipid profiles in treatment-naive UC patients and deep remission UC patients, compared to healthy subjects.

METHODS:

Newly diagnosed treatment-naive UC patients (n = 21), UC patients in deep remission (n = 12), and healthy volunteers (n = 14) were recruited. The state of deep remission was defined by histological and immunological remission demonstrated by a normalized TNF-α gene expression. Mucosa biopsies were collected by colonoscopy. Lipid analysis was performed by means of ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS-MS). In total, 220 lipids from 11 lipid classes were identified and included for data analysis.

RESULTS:

Sixteen lipids showed significant concentration differences between the study groups reflecting the inflammatory state. The majority of significantly up- or down- regulated lipids were phosphatidylethanolamines (PE), and ceramides (Cer). Data analysis revealed that changes in Cer18:1/24:1, Cer18:1/24:0, and PE38:3 were most prominent between the groups. The concentration of Cer18:1/24:1 was highly increased in UC patients' inflamed mucosa compared with UC patients' healed mucosa, whereas, PE38:3 is exclusively present in UC patients' colonic mucosa (both treatment naive and remission state patients). Furthermore, Cer18:1/24:0 was elevated in a stepwise manner from control to remission, and active UC.

CONCLUSION(S):

Lipid analysis in UC revealed alterations in the mucosal lipid composition. In this study, we report several lipids, which might be involved in the inflammatory response and pathogenesis seen in IBD. The PE38:3 is especially interesting in a pathophysiological context since it is found in both active colitis and deep remission but not healthy controls.
P017 Cost burden of CD and UC is significantly higher up to 10 years before diagnosis: A Danish register-based study
Authors: Kasper Vadstrup , Sarah Alulis , Andras Borsi , Tine Jørgensen , Nina Gustafsson , Sandra Stallknecht , Niels Qvist , Pia Munkholm
Published: July 2019

BACKGROUND:

Population-based data on the economic burden of Crohn's disease (CD) and ulcerative colitis (UC) is limited and the burden prior to diagnosis has not yet been reported. This study estimates the ten-year societal costs prior to the diagnoses of CD and UC patients and the 5-year attributable costs after diagnosis in a national patient cohort from Denmark.

METHODS:

In this register study using the Danish National Patient Register and the Danish longitudinal database on employment (the DREAM database), incident CD and UC patients between 2002–2016 were assessed and matched on age and gender with one non-diseased control. Ten-year average annual costs were calculated for cases and controls prior to diagnosis. Five-year attributable costs after the date of diagnosis were also estimated using a difference-in-difference approach. Costs included health care services, prescription medicine, home care services and production loss. Odds ratios for the occurrence of diseases requiring a hospital contact before diagnosis were estimated using logistic regression analyses.

RESULTS:

The study included 10,302 incident CD and 22,144 incident UC patients. Average costs were significantly higher for CD/UC patients than controls throughout the ten-year period prior to diagnosis. The difference increased over time and equaled €3,377 for CD and €2,960 for UC patients in the year before diagnosis. CD/UC patients had significantly more hospital contacts than controls prior to inflammatory bowel disease (IBD) diagnosis, with 51.6% of CD patients and 52.4% of UC patients having other diagnoses related to the digestive system. The average attributable costs were highest the first year after diagnosis, equalling €12,919 per CD patient and €6,501 per UC patient. Hospital admission costs accounted for 36% for CD and 31% for UC patients—prescription medicine for 3% and 7%, respectively.

CONCLUSION(S):

This study provides population-based evidence of the substantial economic burden of CD and UC 10 years prior to and 5 years after diagnosis. These findings may indicate a significant diagnostic delay of CD and UC and warrants more research into the possible causes.
P018 Hypersensitivity reactions to intravenous iron are rare in clinical practice
Authors: Oskar Frigstad Svein , Monirul Islam Md
Published: July 2019

BACKGROUND:

In inflammatory bowel disease (IBD), iron deficiency anemia is the most common systemic complication, and has been reported in 20%–42% of patients, while iron deficiency has been reported in 35-90% of patients. Intravenous iron allows for efficient and well-tolerated treatment in iron deficiency and is routinely used in IBD. Infusion reactions are in clinical studies reported in 1%–3% of iron infusions. The pathogenesis of these infusion reactions is not fully known but complement-activated pseudoallergy seems to be the most important mechanism. The aim of this study was to investigate the safety of iron isomaltoside in clinical practice.

METHODS:

We have performed a prospective registration of all infusion reactions and reports of delayed hypersensitivity following infusions of iron isomaltoside in our hospital from November 2012 to June 2018. The simplified dosing regimen was recommended, and 1,000 mg was used as the defined daily dose in the data analyses. The study was performed as a quality assessement project and was approved by the Regional Data Protection Official. Clinical and epidemiological data were registered, as well as study drug characteristics, dosing, type of hypersensitivity and outcome variables. All hypersensitivity reactions were reported to the health authorities.

RESULTS:

We estimated that a total of 1,240 infusions equivalent to 1,000 mg of iron isomaltoside were given. Acute infusion reactions were reported in 2% (29/1,240) of infusions and delayed hypersensitivity in 0.5% (6/1,240) of infusions. More female (25/29) than male (4/29) patients had acute infusion reactions (P < 0.05). Three patients got infusion reactions on the second infusion and one patient had infusion reactions on both the second and the third infusion. We found no association between dose given and frequency of infusion reactions. No single batch of study drug associated with more infusion reactions was identified. All patients had uneventful recoveries.

CONCLUSION(S):

In this study hypersensitivity following iron isomaltoside was relatively rare in clinical practice. Infusion reactions are most frequently mild and seem to occur more often in women. No association to dose given was shown.
P021 The potential impact of provider gender on IBD management
Authors: Lindsay Clarke , Nadeem Tabbara , Adam Greenfest , Daniel Szvarca , Sarah Turki , Rahma Aldhaheri , Tina Boortalary , Marie Borum
Published: July 2019

BACKGROUND:

Health maintenance guidelines have been published to ensure optimal clinical outcomes for individuals with inflammatory bowel disease (IBD), with recommendations including the evaluation of bone density, eye, and skin health. However, it has been suggested that there is variability in adherence to health maintenance recommendations. This study evaluated both the gender of providers discussing health maintenance with patients, and the overall rate of physicians' recommendations for Dual-energy X-ray absorptiometry (DXA) scans, vitamin D levels, ophthalmologic exams, and skin protective measures at an urban university medical center.

METHODS:

A retrospective chart review was performed evaluating all IBD patients seen at a university gastroenterology clinic over a 5-year period was performed. Patients' IBD diagnosis, recommendations for DXA, vitamin D levels, ophthalmologic exams, and skin protective measures (sunscreen and/or dermatology referral) were obtained. Patient and physician gender were recorded. A database was generated using Microsoft Excel. Statistical analysis was performed using Fisher's Exact Test with significance set at P < 0.05. The study was approved by the IRB.

RESULTS:

393 IBD patients were identified (175 males, 218 females) with mean age of 44.4 (age range: 20–82). 279 (71.0%) had Ulcerative Colitis (UC), 96 (24.4%) had Crohn's disease (CD), 7 (1.8%) with unspecified colitis, and 11 (2.8%) had microscopic colitis. Of the 393 patients, 279 (71.0%) were seen by male providers and 114 (29.0%) were seen by female providers. 249 (63.4%) patients had vitamin D and 110 (28%) had DXA scans performed. Ophthalmologic referrals were offered to 125 (27.8%). 83 (21.1%) were counseled about skin protective measures and given dermatology referrals. Significantly more female providers recommended vitamin D (P = 0.015), DXA screening (P = 0.027), ophthalmologic evaluations (P < 0.0001) and dermatologic referrals (P < 0.0001) compared to male providers. There was no significant difference of the performance of health maintenance recommendations based upon disease type.

CONCLUSION(S):

This study revealed that there was inconsistent adherence to IBD health maintenance recommendations. While female physicians more frequently recommended vitamin D screening, DXA scans, ophthalmologic examinations, and skin evaluations, there was a clear need to improve screening by all physicians. While this study was limited based upon retrospective design, small sample size, and single institution cohort, it provides a foundation for future research that addresses IBD management. Increased efforts to optimize IBD care will improve overall clinical outcomes.
P023 5-Aminosalicylate intolerance is a risk factor for hospitalization in patients with UC
Authors: Yusuke Yoshimatsu , Shinta Mizuno , Makoto Naganuma , Tomohiro Fukuda , Ena Nomura , Kosuke Yoshida , Satoko Umeda , Keiko Ono , Shinya Sugimoto , Kosaku Nanki , Yohei Mikami , Kayoko Kimura , Makoto Mutaguchi , Tomohisa Sujino , Kaoru Takabayashi , Haruhiko Ogata , Yasushi Iwao , Takanori Kanai
Published: July 2019

BACKGROUND:

In recent years, a number of therapeutic drug for patients with ulcerative colitis (UC) has been developed. Meanwhile, 5-aminosalicylic acid (5-ASA) has few serious adverse events, and remains as the first-line drug in induction therapy and maintenance therapy for UC. However, 5-ASA often cause diarrhea, fever and skin rash, and it is often difficult to maintain remission in these cases. There are few studies about the effect of 5-ASA intolerance on the prognosis of patients with UC. In this study, we aimed to clarify the optimal treatment strategy for patients with 5-ASA intolerance by examining the 5-ASA intolerance using the IBD registry of our hospital.

METHODS:

A multi-center retrospective cohort study of UC patients, who visited our hospital from January 2015 to June 2018, was performed, and we enrolled 793 UC patients in IBD registry. We collected the detail clinical information of enrolled patients in the prior year, and the primary outcome was hospitalization. Risk factors for hospitalization were assessed by binary logistic regression analysis. This study was approved by the ethics committee of Keio University School of Medicine (approval number: 20160038).

RESULTS:

We defined 5-ASA intolerance as patients who had at least one in the following symptoms due to 5-ASA administration; headache, gastrointestinal symptoms, cutaneous symptoms, and fever. The rates of 5-ASA intolerance were 28.5% (22/77) in admission group and 5.1% (37/716) in no admission group. Our multivariate analysis showed that the following 3 factors have significant correlations with hospitalization; 5-ASA intolerance (odds ratio (OR) = 5.46, 95% confidence interval (CI) = 2.20–13.5), extent of disease (OR = 9.47, 95% CI = 1.25–71.6), and serum albumin level (OR = 0.122, 95% CI = 0.07–0.20). On the other hand, IM intolerance, age, duration of disease, and 5-ASA non-administration were not significantly correlated with hospitalization. Furthermore, compared with 5-ASA tolerance group, the intolerance group had significantly greater incidences of corticosteroid usage (P < 0.001) and calcineurin inhibitor usage (P < 0.01).

CONCLUSION(S):

It became clear for the first time that 5-ASA intolerance is the risk factor for hospitalization and worsen the prognosis of patients with UC. Therefore, even when we encounter patients with UC who are intolerant to one of the 5-ASAs, switching to another 5-ASA and continuing 5-ASA administration under strict observation may improve the prognosis of patients with UC.
P025 Real-world effectiveness of biologic therapies among patients with moderate-to-severe ulcerative colitis in the United States
Authors: Erin Comerford , Marco DiBonaventura , Timothy Smith , Anthony Louder , David Gruben , Leonardo Salese , Daniel Quirk
Published: July 2019

BACKGROUND:

Treatment goals for ulcerative colitis (UC) focus on inducing a response and maintaining long-term disease remission. The aim of this study was to describe the real-world effectiveness of biologic therapies, as defined by the need for concomitant steroids and UC-related hospitalizations.

METHODS:

This retrospective analysis used the PharMetrics Plus claims data from January 1, 2013 to October 1, 2017. Patients aged ≥18 years with UC (ICD9:556.* or ICD10 K51.*) who newly initiated biologic therapy (adalimumab [ADA], infliximab [IFX], vedolizumab [VEDO], golimumab [GOL]) were included. Patients had to have at least 12 months of continuous enrollment prior to (pre-index) and after (post-index) their first biologic drug claim (index). Patients with Crohn's disease or a history of biologic therapy in the pre-index period were excluded. Steroid use, dosage, and duration were reported descriptively. Time spent steroid free (allowing for an initial 14 week steroid tapering period) and hospitalizations in the post-index period were used as measures of real-world effectiveness.

RESULTS:

N = 3,595 patients with UC were included (51.7% male; age = 42.4 years [SD = 13.6]; disease duration = 1.3 years [SD = 1.0]) with the following treatments at index: N = 2,055 on ADA, N = 1,218 on IFX, N = 152 on GOL, and N = 170 on VEDO. Most patients (84.3%) had used steroids in the pre-index period. Ignoring steroid use during the tapering period, a total of 42.4% of patients were steroid-free in the post-index period. For the 57.6% of patients who used steroids, the mean time to first steroid was 202.1 days (SD = 72.2). This varied by index therapy: ADA = 58.7% used steroids and mean time to first steroid was 201 days, IFX = 55.3% and 207 days, GOL = 66.4% and 181 days, and VEDO = 52.9% and 209 days. The type of steroids use in the post-index period also varied across index biologic treatment. For example, 41.5% of patients treated with ADA used prednisone compared with IFX = 36.7%, GOL = 47.4%, and VEDO = 26.5%. A total of 13.2% of patients had a UC-related hospitalization in the post-index period with, among those hospitalized, an average of 11.4 total days spent in hospital during the post-index period (SD = 14.1). Unadjusted all-cause hospitalization rates and total days hospitalized by treatment were as follows: ADA = 14.0% were hospitalized with 10.4 total days spent in hospital (SD = 13.6); IFX = 19.5% and 11.1 total days (SD = 14.1); GOL = 14.5% with 6.2 total days (SD = 6.6); VEDO = 11.2% with 8.2 total days (SD = 6.5).

CONCLUSION(S):

Almost 60% of UC patients who initiate their first biologic therapy rely on steroids within the first 12 months. A number of patients also experience extended UC-related hospitalization stays. These results suggest an ongoing challenge in managing these patients.
P028 High cytomegalovirus DNA load in mucosal biopsies predicts steroid failure as well as colectomy in acute severe ulcerative colitis
Authors: Saransh Jain , Divya Namdeo , Saurabh Kedia , Pabitro Sahu , Prasenjit Das , Govind Makharia , Lalit Dar , Vineet Ahuja
Published: July 2019

BACKGROUND:

Cytomegalovirus (CMV) reactivation may be responsible for steroid refractory acute severe colitis (ASC), which requires rescue therapy in form of surgery or advanced immunosuppression. The optimum technique for diagnosing CMV colitis in this setting remains unclear. We investigated the role of CMV Quantitative PCR for diagnosing CMV colitis and for predicting of steroid-failure in ASC.

METHODS:

Consecutive patients with ASC satisfying Truelove and Witts' criteria, hospitalized at a single centre from May 2016 to November 2017, were included. The primary outcome measure was steroid-failure defined as colectomy and/or rescue therapy with ciclosporin or infliximab during admission. Oxford criteria, ulcerative colitis index of severity (UCEIS) at day 1 and fecal calprotectin (FCP) at day 3 were used to predict steroid response. Immunohistochemistry (IHC) and quantitative PCR for CMV was done on mucosal biopsies and the results were compared between steroid responders and non-responders.

RESULTS:

Of 37 patients (Mean age: 35 ± 12 years, 70% males), 14 (38%) failed iv corticosteroids and 8 (25%) required surgery. Although IHC for CMV was not different between steroid failures and responders (29% vs 17%, P = 0.40), patients with steroid failure had a significantly higher median level of mucosal CMV DNA (7,840 [0–2,700,000] vs 112 [0–34,459] copies/mg, P = 0.03). Significantly greater number of patients with steroid failure had CMV DNA count >1,000 copies/mg (71% vs 26%, P = 0.007). CMV DNA count >1,000 copies/mg (odds ratio 6.5 [95% confidence interval 1.3–33, P = 0.03]) and positive oxford criterion on day 3 of iv corticosteroids (OR 6 [95% CI 1.2–30, P = 0.03]) were independent predictors of steroid-failure and need for rescue therapy/colectomy.

CONCLUSION(S):

CMV DNA quantification in mucosal biopsy can detect CMV colitis and predict steroid failure in acute severe colitis with reasonable accuracy.
P029 Background factors associated with the prognosis of patients with Crohn's disease: A single-center, retrospective study
Authors: Kaoru Ezaki
Published: July 2019

BACKGROUND:

Crohn's disease (CD) is a chronic and intractable granulomatous disease. Its onset often occurs at an earlier age, with disease severity being greater in early-onset cases than in adult-onset cases. Many CD patients, mainly adults, have been treated at our hospital in Japan. However, limited studies have examined background factors that affect prognosis in Japanese patients with CD. Therefore, this study aimed to examine background factors in CD patients treated at our hospital.

METHODS:

According to the age of disease onset, patients were divided into those less than 17 years of age (early-onset inflammatory bowel disease [EO-IBD] and those 17 years of age and older (late-onset IBD [LO-IBD]). The primary endpoint was the cumulative surgery-free rate, and the secondary endpoint was the rate of treatment not requiring biological agents.

RESULTS:

We evaluated 1,148 patients with CD who visited our hospital between 1985 and October 2015. The EO-IBD and LO-IBD groups included 257 (22.4%) and 891 (77.6%) patients, respectively. We could evaluate the disease course until surgery in 1,112 patients. The numbers of patients in the EO-IBD and LO-IBD groups who underwent surgery were 158 (of 251 evaluable patients; 63%) and 496 (of 861 evaluable patients; 58%), respectively, and there was no significant difference between the groups (P = 0.13). The cumulative surgery-free rates, as determined using the Kaplan–Meier method, were 55% and 21% at 10 and 20 years, respectively, in the EO-IBD group and 51% and 26% at 10 and 20 years, respectively, in the LO-IBD group (P = 0.59). In total, 1,136 patients were treated with biological agents; the numbers of patients in the EO-IBD and LO-IBD groups were 164 (of 256 evaluable patients; 64%) and 465 (of 880 evaluable patients; 53%), respectively, and there was a significant difference between the groups (P = 0.001). The cumulative rates of treatment not requiring biological agents, as determined using the Kaplan–Meier method, were 65% and 39% at 10 and 20 years, respectively, in the EO-IBD group and 72% and 49% at 10 and 20 years, respectively, in the LO-IBD group (P = 0.03).

CONCLUSION(S):

The cumulative surgery-free rate was not different between the EO-IBD and LO-IBD groups, whereas the rate of treatment with biological agents was greater in the EO-IBD group than in the LO-IBD group. Thus, the severity of EO-IBD might progress faster than that of LO-IBD. This finding should be considered in the follow-up of patients.
P031 Systematic-analysis of injection-site pain from administration of subcutaneous adalimumab biosimilar FKB327 versus the adalimumab reference product humira via different methods
Authors: Herbert Kellner , Mark Genovese , Malcolm Boyce , Takuma Yonemura , Takahiro Ito , Rieke Alten
Published: July 2019

BACKGROUND:

FKB327 is a proposed biosimilar of the adalimumab reference product (RP). Several studies in both healthy volunteers and patients with active rheumatoid arthritis (RA) were undertaken, the results of which have been reported elsewhere. The formulation excipients of the biosimilar product differ from that of the RP, and different injection-site pain with subcutaneous injection has been reported. The current meta-analysis examines pooled data from these studies in relation to the amount of injection-site pain resulting from using prefilled syringes (PFS) versus auto-injectors (AI) versus regular syringes (RS) and the proposed biosimilar, FKB327, versus the RP.

METHODS:

Data from 4 studies, FKB327-001, -002, -003, and -004, were pooled in an effort to compare injection-site pain upon subcutaneous administration of FKB327 versus the RP (citrate-containing formulation of the RP (40 mg/0.8 mL). Study FKB327-001, in healthy volunteers (n = 180), involved a single subcutaneous dose of either FKB327 or the RP. Study FKB327-004 was a similar study in healthy Japanese volunteers (n = 130). Study FKB327-002 was a randomized (FKB327 with RS or the RP), double-blind, multiple-dose study in patients with active RA. This was followed by Study FKB327-003, in which patients were rerandomized to receive either FKB327-PFS or the RP in the randomization phase, followed by an open-label extension phase of the study, in which AI was introduced. As patients were continued on treatment or switched during the course of the FKB327-002 and -003 studies, the injection-site pain was assessed at the first dosing occasion of FKB327 or the RP (n = 691). Data from all 4 studies were examined by meta-analysis of the visual analog scale (VAS) using a 100-mm horizontal scale for FKB327 versus the RP and for comparison of AI, PFS, and RS.

RESULTS:

Data were analyzed from a total of 2007 assessments in 1,001 subjects. A linear mixed model of the VAS in mm for the RP versus FKB327 across all 4 studies showed a 12.6-point improvement in the score for FKB327 versus the RP (95% confidence interval [CI], –14.3 to –10.8; P < 0.001). For the AI and PFS used for FKB327 administration, AI showed a 1.7-point improvement in VAS compared with PFS (95% CI, –3.3 to –0.1; P = 0.035). Gender, age, body weight, and population (healthy subject or patient) were not identified for differences in injection-site pain.

CONCLUSION(S):

FKB327 showed a significant advantage in terms of injection-site pain compared with the RP, as well as lack of inferiority for both AI and PFS versus RS.
P032 The incidence of Cytomegalovirus in acute severe colitis in hospitalized patients with inflammatory bowel disease
Authors: Andrew Ho , Ryan Nock , Thomas Myint
Published: July 2019

BACKGROUND:

An association between cytomegalovirus (CMV) and acute severe inflammatory bowel disease (IBD) colitis has been demonstrated in prior studies. However, it is unclear whether this association indicates CMV as a causative pathogen in triggering severe flares. This study aimed to assess the incidence of CMV in IBD patients admitted to a community-based, safety-net hospital for acute severe colitis and evaluate risk factors and outcomes for CMV colitis.

METHODS:

A retrospective case control study involving all IBD patients admitted from 2013-2017 to a county hospital with acute severe colitis. Data was collected from the hospital's electronic medical record. Data extracted included demographics, IBD type, symptoms on admission, and types of medications used including steroids or biologic therapy. We calculated odds ratios (OR) and confidence intervals for multiple risk factors.

RESULTS:

Among 45 IBD patients, there were 80 separate hospitalizations that met criteria for acute severe colitis based on Truelove and Witt's criteria. CMV infection was detected in 3 out of 80 (4%) admissions. 67% and 33% of CMV cases had received prior treatment with high dose steroids & biologics respectively, compared to 33% & 29% of cases without CMV infection (OR 4.16, P-value 0.25; OR 1.25, P-value 0.86). Of patients with CMV infection, 67% had ulcerative colitis (UC), 33% Crohn's Disease (CD), 100% were age < 40, 33% were male and 67% female, none had cancer or HIV, and 33% had cytopenia. Of patients without CMV infection, 71% had UC, 29% had CD, 52% were age < 40, 58% were male and 42% female, 1% had cancer, 1% had HIV, and 8% had cytopenia. The course of CMV positive cases was similar to CMV negative cases: 1 of the 3 cases of CMV cases was steroid refractory, 1 of 3 cases was immediately treated with biologics, and no case progressed to colectomy. In CMV negative cases, 20 of 77 were steroid refractory, 32 of 77 received biologics, and 9 of 77 underwent colectomy.

CONCLUSION(S):

Three out of 80 cases of acute severe colitis were found to have CMV infection, a figure lower than in previous studies. In our study, CMV is infrequently associated with colitis and of those who had CMV, none required colectomy. Of the risk factors that were evaluated, none were significantly associated with CMV colitis though this may be due to the small number of cases. Of note, there was a non-significant trend towards CMV infection with prior high dose steroids, age < 40 years, and IBD duration < 1 year. More prospective studies are needed to evaluate the true risk of CMV infection in acute severe colitis.
P038 Persistent inflammatory markers and deregulated immune response in clinical remission Crohn's disease patients treated with infliximab
Authors: Murillo Duarte-Silva , Rogerio Parra , Marley Feitosa , Omar Féres , Joaquim Rocha José , Cristina Cardoso
Published: July 2019

BACKGROUND:

The development of Inflammatory Bowel Diseases (IBD) comprises an imbalance among gut microbiota, genetic susceptibility and exacerbated immune responses, which predispose to chronic inflammation in affected patients, who are usually treated with biological agents such as anti-tumor necrosis factor-α (TNF-α). Despite that, even during clinical remission periods, Crohn’s disease (CD) patients may still present endoscopic disease activity and possibly a residual systemic inflammatory response. Therefore, in this study we aimed to evaluate the responsiveness and immune profile of peripheral blood mononuclear cells (PBMC) of infliximab-treated patients, as well as the relationship between the altered responses and the clinical disease presentation.

METHODS:

We enrolled 20 healthy controls (HC) and 39 CD patients, which were classified according to the Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for Crohn’s Disease (SES-CD). All were using anti-TNF-α therapy (infliximab), including 61.5% in combination with Azathioprine.

RESULTS:

Although 94% of the patients were in clinical remission, 51.3% presented disease mucosal activity. Considering the Montreal classification, 12.8% had colonic disease, while 33.4% had ileal and 53.8% ileocolonic disease. Most the patients developed complications, being 20.5% stenosis and 35.9% structuring disease, while 59% had perianal disease. The immunophenotyping identification of PBMC by flow cytometry showed increased CD14+ and CD14++CD16+ monocytes in CD, indicating a tendency towards an inflammatory response because of the increased CD16 expression, along with augmented NKT and decreased NK cells and B lymphocytes. Considering the population of regulatory lymphocytes, CD patients had increased CD4+CD25+CTLA-4+ and CD4+CD25+FOXP3+ cells, together with augmented expression of CTLA-4 and FOXP3 in CD4+CD25- and CD4+CD25+ lymphocytes, indicating the raising of an important systemic counter regulatory response. Nevertheless, there was an increase in the inflammatory cytokine IL-6 in plasma and when PBMC was restimulated in vitro with bacterial-derived lipopolysaccharide (LPS), CD patients produced more TNF than healthy controls. Indeed, plasma dosage of LPS pointed to increased detection in CD samples, suggesting that these patients still present bacteria translocation to circulation.

CONCLUSION(S):

Even in clinical remission, CD patients had a relevant systemic inflammatory response together with increased regulatory population, probably elicited in an attempt to achieve immune-regulation after biological therapy. Financial support: Fapesp # 2017/08651-1.
P040 Vasculitis in a patient with refractory Crohn's disease
Authors: Christina Silveira Mabel , Gustavo Vilar , Antonio Balestrim Filho , Joaquim Rocha José , Omar Féres , Marley Feitosa , Rogerio Parra
Published: July 2019

BACKGROUND:

Crohn's disease (CD) is associated with a variety of cutaneous manifestations, many of which parallel disease activity. Leukocytoclastic vasculitis (LV) is a rare and underdiagnosed cutaneous manifestation of CD.

CASE:

A twenty-year old woman presented to our unit with a rash affecting her lower extremities eleven days after ileocolic resection and ileostomy for refractory CD. Her past medical history included the diagnosis of penetrating CD for 3-years (anti-TNF refractory). Investigations revealed: normal full blood count and electrolytes, negative serologies (HIV, HBV, syphilis, HCV), normal C-reactive protein (CRP), negative rheumatoid factor, negative anti-nuclear antibodies (ANA), positive antineutrophil cytoplasmic autoantibody (ANCA). Skin biopsy diagnosed LV, characterized by angiocentric neutrophilic infiltrate with normal epidermis and no granulomata or fibrinoid necrosis.

DISCUSSION:

LV is an immune-complex syndrome characterized by palpable purpura commonly located in the lower limbs and ankles. It is a rare skin manifestation of CD. Lesions range from 1mm to several centimeters. The condition may also present as urticarial papules, nodules, vesicles, plaques, hemorrhagic bullae and necrotic ulcers. Fever, arthralgia, myalgia and ankle swelling may be present. It is often associated with active intestinal disease. It is believed that direct exposure of immune cells of inflamed intestinal mucosa to fecal antigens may lead to formation of immune complexes, deposited in vessel walls causing vasculitis. LV may also be triggered by medications, infections, surgery, chemicals and other autoimmune diseases. Our patient improved spontaneously after few weeks of surgery. During follow-up, she had no signs of skin lesions or intestinal flares.

CONCLUSION:

LV is rare a small-vessel vasculitis that may be observed in inflammatory bowel disease patients. Treatment of the predisposing condition is essential in patients with skin-limited disease.
P041 Increased healthcare utilization by Medicaid patients with inflammatory bowel disease at a tertiary care center
Authors: Jordan Axelrad , Rajani Sharma , Monika Laszkowska , Richard Rosenberg , Benjamin Lebwohl
Published: July 2019

BACKGROUND:

Low socioeconomic status has been linked to numerous poor health outcomes, but there is little data regarding the impact of insurance status on inflammatory bowel disease (IBD) outcomes. We aimed to characterize utilization of healthcare resources by patients with IBD based on health insurance status, using Medicaid enrollment as a proxy for low socioeconomic status.

METHODS:

We retrospectively identified adult patients with IBD engaged in a colorectal cancer surveillance colonoscopy program from July 2007 to June 2017. Our primary outcomes included emergency department (ED) visits, inpatient hospitalizations, biologic infusions, and steroid exposure, stratified by insurance status. We compared patients who had ever been enrolled in Medicaid to all other patients.

RESULTS:

Of 947 patients with IBD, 221 (23%) ever had Medicaid. Compared to other insurances, Medicaid patients had significantly higher rates of ever being admitted to the hospital (77.6% vs 42.6%, P < 0.0001) or ever visiting the ED (90.5% vs 38.4%, P < 0.0001). When adjusted for sex, age at first colonoscopy, race, and ethnicity, Medicaid patients had a higher rate of inpatient hospitalizations (Rate ratio [RR] 2.95; 95% CI 2.59–3.36) and ED visits (RR 4.24; 95% CI 3.82–4.70) compared to patients with other insurance. Medicaid patients had significantly higher prevalence of requiring steroids (62.4% vs 37.7%, P < 0.0001) and after adjusting for the same factors, the odds of requiring steroids in the Medicaid population was increased (OR 3.77; 95% CI 2.53–5.62).

CONCLUSION(S):

Medicaid insurance was a significant predictor of IBD care and outcomes. Patients with Medicaid may have less engagement in IBD care and seek emergency care more often.
P045 Do Levels Matter? Maintaining Anti-TNF Class After Secondary Loss of Response to Adalimumab in Inflammatory Bowel Disease
Authors: Christina Bauer , Adam Younis , Millie Long , Hans Herfarth , Edward Barnes
Published: July 2019

BACKGROUND:

Anti-tumor necrosis factor (Anti-TNF) biologic therapies have evolved as a mainstay of treatment for inflammatory bowel disease (IBD). However, 10%–20% of patients are primary non-responders to anti-TNF in clinical series and up to 40% of patients lose response to treatment over time. Current guidelines suggest that treatment failure in the setting of adequate drug concentrations are due to mechanistic failure and should be switched out of the anti-TNF class. Our aim was to assess the efficacy of switching to infliximab, rather than changing out of class, in patients with secondary loss of response to adalimumab who had a therapeutic drug level.

METHODS:

A retrospective chart review identified patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with adalimumab within the University of North Carolina Inflammatory Bowel Disease clinic between January 1, 2007 and December 31, 2017. Patients with a therapeutic adalimumab level and treatment failure and who were subsequently treated with infliximab were included in the study.

RESULTS:

There were a total of 16 patients with therapeutic adalimumab levels (>5 μg/mL) and no antibody formation with treatment failure. In this population, 11 of the patients had CD, 3 patients had inflammatory bowel disease undifferentiated (IBDU) and 2 had UC. Ileocolonic CD (45.5%) and penetrating disease (54.4%) were the most common phenotypes. All patients had secondary loss of response to adalimumab and 87.5% had been increased to weekly dosing. Mean adalimumab level was 9.8 ± 6.8 μg/mL prior to switching to infliximab. Thirteen patients (81.3%) achieved clinical response with infliximab at 14 weeks and of the 8 patients with endoscopic assessments, 100% achieved endoscopic remission (5 with UC/IBDU and 3 with CD). There were a total of 6 patients in a sensitivity analysis assessing therapeutic levels >7 μg/mL. All patients were female, however all other characteristics in this group were similar to those patients evaluated with a therapeutic threshold of 5 μg/mL, including the rate of clinical response at 14 weeks (83.3%). When compared to 28 patients with adalimumab levels <5 μg/mL, there was no significant difference in clinical response at 14 weeks (P = 0.692).

CONCLUSION(S):

Switching within class to infliximab after secondary loss of response to adalimumab with a therapeutic level achieved clinical remission at 14 weeks in 81.3% of patients, and appears to be an acceptable strategy in selected patients. Therapeutic drug levels alone are not predictive of clinical response to a second anti-TNF.
P046 Complementary and alternative medicine in patients with inflammatory bowel disease 20 years after diagnosis: Results from the IBSEN study
Authors: Randi Opheim , Jørgen Jahnsen , Tomm Bernklev , Ole Høie , Gert Huppertz-Hauss , Bjørn Moum
Published: July 2019

BACKGROUND:

Use of complementary and alternative medicine (CAM) is common among IBD patients (1). The CAM modalities used include a wide specter of health care practices and therapies (2). In a previous study from this population, we found that almost one third of the patients used CAM 10 years after diagnosis (3). The aim of this follow-up study was to assess CAM use in IBD patients 20 years after diagnosis.

METHODS:

The Inflammatory Bowel South-Eastern Norway (IBSEN) study is a population based study with a prospective design. From January 1990 to December 1993, all newly diagnosed patients with IBD from a well defined area in South Eastern Norway were included in the cohort. The 20-year follow-up was conducted between 2011 and 2014 and included a structured interview, a review of patient records, a clinical examination, laboratory tests, and a questionnaire regarding CAM use.

RESULTS:

Of the 599 invited to attend the 20-year follow - up visit, 78.5% (UC = 314, CD = 156) participated in the follow- up study, whereof 93% (UC = 293 and CD = 146) completed the CAM questionnaire, 49% men. In total 122/439 (28%) reported use of CAM for their IBD, and 6% reported current CAM use. A significantly higher proportion women than men (60% vs 40%, P = 0.02) reported to use CAM. CAM users were younger (49 years) than the non-users (56 years), P < 0.001. A significantly higher proportion CD patients compared to UC patients (34% vs 25%, P = 0.04) reported CAM use. Treatment with CAM occurred more frequently in patients with more than one relapse the last year than in patients in remission (35% vs 21%, P = 0.003). The 3 most commonly used types of CAM were acupuncture 63/122 (52%), homeopathy 49/122 (40%) and herbal medicine 47/122 (39%). The 2 most common reasons for using CAM was as (1) a supplement to conventional treatment (41%) and (2) lack of effect from conventional medicine (32%).

CONCLUSION(S):

One third of the IBD patients reported CAM use 20 years after diagnosis. Prevalence of CAM use was comparable in the 10-year and 20-year follow- up. CAM use was more common among women, in younger patients, in UC patients, and in those with disease activity.
P047  Relevant factors and significant endoscopic findings for detecting UC-associated neoplasms using pan-colonic NBI surveillance colonoscopy: A sub-analysis of navigator study
Authors: Kenji Watanabe , Reo Kawano , Masakazu Nishishita , Fumio Shimamoto , Takumi Fukuchi , Esaki Motohiro , Shiro Oka , Shigehiko Fujii , Fumihito Hirai , Kazuki Kakimoto , Takuya Inoue , Ryoich Nozaki , Hiroshi Kashida , Ken Takeuchi , Naoki Ohmiya , Masayuki Saruta , Shoichi Saito , Shinji Tanaka , Yoichi Ajioka , Hisao Tajiri
Published: July 2019

BACKGROUND:

We recently reported the results of a prospective multicenter randomised controlled trial comparing pancolonic observation using a newly developed NBI (CF-HQ290I) and panchromoendoscopy (PCE) for surveillance colonoscopy in UC patients. The results revealed that the NBI observation was not inferior to PCE for the detection of both neoplastic lesions (13.4% vs 9.0%; P = 0.33) and colitis-associated dysplasia or cancer (CC/D) (6.3% vs 4.9%; P = 0.86). Moreover, the total examination time of NBI (15.0 min) was significantly shorter than that of PCE (19.8 min) (P < 0.01). This sub-analysis aimed to evaluate the relevant factors or NBI findings of the background mucosa of CC/D in the preceding Navigator Study (UMIN000013527).

METHODS:

In total, 263 patients were randomised to the PCE group (n = 130) and the NBI group (n = 133). Surveillance colonoscopy in both groups was performed mainly with targeted biopsy. The pathological diagnoses were made by 2 expert pathologists who performed including immunohistochemical staining (p53, Ki-67) while being blinded to clinical information.

RESULTS:

A total of 21 sporadic adenoma, 3 traditional serrated adenoma, 2 sessile serrated adenoma/polyp, 10 indefinite for dysplasia, 9 low grade dysplsisadysplasia, and 7 high grade dysplasia or cancer cases were detected. There was no statistical difference for in the contents of these detected lesions between the 2 groups (P = 0.91). The median number of biopsy samples was not different between the 2 groups (1.80/case in NBI, 1.85/case in PCE; P = 0.88). Multivariate analysis demonstrated that age (OR 1.05, 95% CI 1.02–1.08, P < 0.01) and past history of CC/D (OR 4.26, 95% CI 1.29–14.05, P = 0.02) were the relevant factors for the detection of neoplastic lesions, and past history of CC/D (OR 5.70, 95% CI 1.33–24.50, P = 0.02) was the relevant factor for the detection of CC/D. CC/D was significantly more frequently detected than sporadic adenoma in cases in which the background mucosa had an obscure vascular pattern or scar rather than a fair view of the vascular pattern or out of range for inflammation (OR 25.0, 95% CI 3.80–164.4, P < 0.01).

CONCLUSION(S):

In the Navigator Study, a past history of endoscopic resection or detection of dysplasia on random biopsy was the relevant factor for the detection of CC/D. The NBI findings of the background mucosa were useful in differentiating CC/D and sporadic adenoma.
P050 Clinical outcomes of refractory Crohn's disease following hematopoietic stem cell transplantation: A single center experience
Authors: Natália Queiroz , Luisa Barros , Matheus Azevedo , Alexandre Carlos , Luciane Milani , Beatriz Rocha , Jane Oba , André Leite , Aytan Sipahi , Adérson Damião
Published: July 2019

BACKGROUND:

Hematopoietic stem cell transplantation (HSCT) has recently been described as an option for treatment of patients with refractory Crohn’s disease in whom surgical treatment is not possible or desired (1). However, the reported long term follow up of patients submitted to this treatment is usually no longer than12 months (2).

METHODS:

Data from 5 patients who had undergone HSCT due to refractory Crohn's disease followed in the IBD unit of Gastroenterology Division of the Clinics Hospital of the University of São Paulo was retrospectively collected based on medical records.

RESULTS:

From 2014 to 2016, 5 patients were transplanted: 4 male and one female. Median age was 27 years old [20–43] and mean disease duration was 6 years [3–8]. Two of them were active smokers. Location of disease was ileocolonic in 4 patients and colonic in the other. Three of them had inflammatory behavior, one stricturing and the other penetrating disease (perianal fistula). One patient had had previous right colectomy before HSCT. All patients had failed at least one immunosuppressor (Azathioprine and/or Methotrexate) and 2 anti-TNFs (Infliximab and Adalimumab). Only one patient was treated with anti-integrin (Vedolizumab) prior to HSCT. Patients underwent annual lower GI endoscopies after transplantation during a 36-month median follow-up. After HSCT, all patients had clinical remission for at least 6 months. Endoscopic remission (defined by absent of ulcers) was observed in only one patient in the first year. This patient was non smoker, had colonic inflammatory disease and no surgical history. Four patients relapsed during the first year and required retreatment with immunomodulator and/or anti-TNF. Half of them (n = 2) achieved deep remission after 36 months of follow up. None required surgery or died after HSTC.

CONCLUSION(S):

This long term follow-up case series have demonstrated that HSCT may be a reasonable option to very refractory CD patients in order to avoid radical surgical procedures. Even when endoscopic remission is not obtained after transplantation, refractory patients can become responders to medications previously used.
P051 MR-enterography with diffusion weighted imaging and apparent diffusion coefficient map for assessing inflammatory bowel disease in children and adolescents
Authors: Itsuhiro Oka , Osamu Miyazaki , Ichiro Takeuchi , Hirotaka Shimizu , Toshiaki Shimizu , Katsuhiro Arai
Published: July 2019

BACKGROUND:

Endoscopy has been considered as the gold standard for the assessment of gastrointestinal inflammation, however, it can only evaluate superficial mucosal layers. Crohn's disease could cause transmural inflammation in any part of the gastrointestinal tract. As a result, stenosis, perforation, and internal/external fistula formation can complicate with this inflammation, and assessing the inflammatory activity of the bowel wall, not limited to the superficial intestinal mucosa, would lead to the proper diagnosis as well as management to minimize complication in patients with inflammatory bowel disease (IBD). Small bowel inflammation can be evaluated by both magnetic resonance imaging (MRI) and computed tomography (CT), and they have shown similar accuracy and sensitivity for the detection of active inflammation. Recent studies have addressed the utility of Diffusion Weighted Imaging (DWI) and apparent diffusion coefficient (ADC) map in adult, while there have been few studies using these modalities in children and adolescents. The aim of this study was to explore the usefulness of ADC values in children with IBD.

METHODS:

Children and adolescents with IBD that required MR-enterography (free-breathing axial DWI with 2 b (0 and 800 s/mm2) was included) for the assessment of small intestinal lesion at a Japanese children's hospital were retrospectively reviewed. A total of 14 children and adolescents with IBD (12 CD and 2 UC), aged 5 to 23 years who had undergone MR-enterography from 2017 to 2018. Mean restricted ADC (r-ADC) value was obtained in a set of value (3 points of thickened bowel wall in all patients [n = 14]). Also, mean non-restricted ADC (nr-ADC) value was obtained from normal bowel wall as well as r-ADC described above. Fourteen age-matched control patients that had undergone MR-enterography were identified. In addition, mean ADC value of non-IBD patients (ni-ADC) was obtained from normal intestinal wall as a control group (e.g., neuroblastoma, n = 14). These values were compared using t-test. P < 0.05 were considered to indicate statistical significance.

RESULTS:

The r-ADC values were significantly lower than the nr-ADC values (1.118 ± 0.271 × 10−3 mm2/s vs 2.119 ± 0.252 × 10−3 mm2/s; P < 0.01). However, there was no significant difference between ni-ADC and nr-ADC (2.15 ± 0.217 × 10−3 mm2/s vs 2.119 ± 0.2519 × 10−3 mm2/s; P = 0.556).

CONCLUSION(S):

DWI and ADC map were useful in locating actively inflamed bowel segments. MR-enterography with DWI and ADC map appeared an excellent modality to assess intestinal inflammation that can be repeatedly used without radiation exposure, even in pediatric patients. Further studies to investigate for the threshold of ADC value that can be used for children with IBD should be considered.