bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.