bluuebunny/crossref_metadata_2025_split huggingface dataset:
689 Early Improvement After Intravenous Ustekinumab Induction in Patients With Ulcerative Colitis: Results From the UNIFI Induction Trial
Authors: Sands Bruce E. , Abreu Maria T. , Marano Colleen , Baker Thomas , O'Brien Christopher , Zhang Hongyan , Johanns Jewel , Rowbotham David , Leong Rupert W. L. , Danese Silvio 
Published: October 2019

INTRODUCTION:
The UNIFI induction study evaluated the efficacy and safety of ustekinumab (UST) in patients with moderately to severely active ulcerative colitis (UC) after a single intravenous infusion. In this analysis, we evaluated the rapidity of the onset of the treatment effect.

METHODS:
Eligible patients were randomly assigned to placebo (PBO) or UST 130 mg or ∼6 mg/kg. Patients recorded stool frequency and categorized rectal bleeding daily for the 7 days before each visit. Partial Mayo scores were calculated at baseline and Week 2 using the average of the stool frequency and rectal bleeding scores from the most recent consecutive 3-day period before the visit and the physician's global assessment score recorded at the visit. C-reactive protein (CRP) and fecal biomarkers were measured at baseline and Day 14.

RESULTS:
At baseline, the mean 3-day average daily stool frequency was 7.0 in the PBO group, 6.9 in the UST 130-mg group, and 7.0 in the UST ∼6-mg/kg group. Patients receiving UST showed greater reductions in the daily number of stools compared with PBO as soon as the first assessment time point at Day 7. Mean changes from baseline in daily stool frequency were -0.7 for PBO, -1.0 for UST 130-mg (P = 0.098), and -1.2 for UST ∼6-mg/kg group (P = 0.018) by Day 7, respectively, and -0.9, -1.6 (P < 0.001), and -1.9 (P < 0.001) by Day 13, respectively (Figure 1). Rectal bleeding scores at baseline and Week 2 are summarized in Figure 2. Patients receiving UST showed significantly greater improvement from baseline to Day 14 in partial Mayo score and CRP (Table, P < 0.001 for all comparisons of UST vs PBO). Differences between the UST and PBO treatment groups in mean changes from baseline to Day 14 in fecal calprotectin did not reach significance (PBO -33.96 mg/kg, UST 130 mg 79.12 mg/kg [P = 0.875], UST ∼6 mg/kg -412.68 mg/kg [P = 0.152]). However, patients receiving UST showed significantly greater improvement in fecal calprotectin at Week 4 (mean changes from baseline: PBO -226.78 mg/kg, UST 130 mg -881.22 mg/kg [P = 0.013], UST ∼6 mg/kg -802.75 mg/kg [P < 0.001]). Similar results were observed for fecal lactoferrin.

CONCLUSION:
The effect of UST began rapidly after induction, with symptomatic improvement and reduction of systemic inflammation seen as early as the first assessments at Days 7 and 14, respectively.
693 Risk Factors for and Frequency of Steroid Utilization in Inflammatory Bowel Disease Patients Seen in the Emergency Department
Authors: Glassner Kerri , Jones-Pauley Michelle , Gajula Prianka , Euers Lindsay , Ezeana Chika F. , Puppala Mamta , Wang Lin , Wong Stephen T. , Oglat Ayah , Nickerson Stephanie , Abraham Bincy 
Published: October 2019

INTRODUCTION:
Although biologics and immunomodulators are commonly prescribed as maintenance therapy in patients with inflammatory bowel disease (IBD), steroids continue to be prescribed during acute flares and in refractory disease. There are significant risks associated with steroids and strategies are needed to decrease their utilization and optimize the care of IBD patients. Our aim was to identify the risk factors for and frequency of steroid utilization in IBD patients seen in our ER.

METHODS:
A retrospective analysis of IBD patients seen at Houston Methodist Hospital ER from 2014 to 2017 was performed using ICD codes to identify patients with Crohn's disease, ulcerative colitis or indeterminate colitis from the electronic medical record. There were 559 unique patients with 1489 unique visits confirmed after charts were individually reviewed for accuracy. Data was collected on demographics including age, sex, and ethnicity; medications (biologic, immunomodulators, and steroids); and imaging (CT of the abdomen/pelvis). Primary reason for the ER visit, and whether steroids were given specifically for IBD was documented.

RESULTS:
Of the 559 patients with ER visits, 61% were female with an average age of 50 (range 18-95). There were 65% with Crohn's disease, 34% with ulcerative colitis, and less than 1% had indeterminate IBD. Of these, 23% were on a biologic and 15% on an immunomodulator. Steroids were given for IBD during the ER visit or after hospital admission in 152 unique patients (27%), during 236 visits (16%). Among these patients, the average age was 44, 56% were female, 67% had Crohn's disease, 32% ulcerative colitis, 31% were on a biologic, and 24% an immunomodulator. Increasing age was associated with decreased steroid use, P = 4.039 × 10-09, R -0.00084. Males were more likely to be given steroids, P = 0.005, R = 0.048, as were those on a biologic, P = 0.001, R = 0.059, or immunomodulator, P = 2.617 × 10-16, R = 0.131. Steroid use was also more common in those with IBD as the primary reason for the ER visit, P = <2.2 × 10-16, R = 0.228.

CONCLUSION:
Steroid use during ER and hospital admissions in our IBD population was found to be common despite the increasing availability of alternative medications. However, steroid use was associated with biologic and immunomodulator use, suggestive that the ongoing utilization tends to occur in patients with more severe disease. Steroid use was also found to be more common in male patients, and in those of younger age which may be explained by increased use at diagnosis.
694 Female Gender Associated With Decreased Inpatient Complications in Patients With Ulcerative Colitis
Authors: Kroner Paul T. , Kesler Alex M. , Corral Juan E. , Riley Guillermo , Lukens Frank 
Published: October 2019

INTRODUCTION:
Gender in ulcerative colitis (UC) is a well-studied topic with contradicting results with a slight male predominance seen in large population based studies in Olmsted County, Minnesota, while other studies have shown a slight female predominance. Yet, the relationship between UC and gender is not well-understood. Hence, it is unclear what is responsible for differences in gender. The aim of this study is to assess the inpatient prevalence and inpatients outcomes of UC by gender.

METHODS:
Case-control study using the NIS 2016, the largest public inpatient database in the US. All patients with ICD9-10CM codes for UC were included. None were excluded. Female patients were identified within the database using the female gender indicator. The primary outcome was determining the odds of UC in female patients compared to males. Secondary outcomes included determining inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and inflation-adjusted total hospital costs and charges. Propensity score matching was used to create a matching population for Charlson Comorbidity Index and age. Multivariate regression analyses were used to adjust for income in patient zip code, hospital region, location, size and teaching status.

RESULTS:
A total of 38, 950 patients with UC were identified and propensity matched for selected covariates. The mean patient age was 45, and 47.2% were female. For the primary outcome, females had decreased adjusted odds (aOR: 0.92, P < 0.01) of being admitted for UC. For secondary outcomes, female patients displayed lower adjusted odds of multi-organ failure, being placed on TPN, and undergoing colectomy. Females also had lower adjusted mean hospital costs, charges, and length of stay (LOS). All adjusted odds and means are displayed in Table 1.

CONCLUSION:
Females have lower inpatient prevalence of UC, complications, and economic burden compared to males. This reinforces the slight male predominance that was seen in the older Olmstead County population-based studies. One can speculate that the difference in complications, costs, charges, and LOS indicate that females have less severe disease at hospital admission. Numerous studies have examined the effect of gender on disease severity and outcomes, and there continues to be conflicting data. Thus, future studies are needed to determine what contributes to the variation in disease prevalence and course by gender, and possibly better tailor treatment regimens by gender.
696 FUT2 Genotype Is Not Associated With Disease Phenotype or Outcomes in Patients With Crohn's Disease
Authors: Wang Wenfei , Melinamani Shruti , Alexander Chervonsky , Bermea Rene , Sakuraba Atsushi , Dalal Sushila R. , Cohen Russell D. , Weber Christopher , Rubin David T. , Pekow Joel 
Published: October 2019

INTRODUCTION:
The fucosyltransferase 2 gene (FUT2) is responsible for the regulation of mucosal blood type antigens which can act as receptors for bacterial adhesion and regulate intestinal flora. A homozygous non-sense mutation in this gene leads to the absence of these antigens, termed FUT2 nonsecretor status, and is associated with the development of Crohn's disease (CD). The mechanism of this association is likely via changes in homeostatic symbiosis thus promoting development of inflammation. However, the impact of FUT2 genotype on CD phenotype and outcomes is not known.

METHODS:
Patients were prospectively enrolled into a single center translational IBD registry. All patients with CD who had available DNA extracted from peripheral blood for genotyping were included. Genotyping was performed using the rs601338-AA SNP, which represents the nonsense mutation (428GA) shown to be causing nonsecretor status. Baseline demographics, disease phenotype, CD-related surgery, and hospitalization were also assessed retrospectively and statistically compared based on FUT2 genotype.

RESULTS:
635 patients with CD were studied including 178 wild-type (WT), 314 heterozygous (HET) and 143 homozygous (O) patients. The mean duration of follow up was 8 years 2 months. There were no significant differences detected between genotypes when comparing sex, race, smoking, body-mass index, and age of onset. Presence of extra-intestinal manifestations including arthritis, uveitis, erythema nodosum, pyoderma gangrenosum, and PSC, as well as disease location and behavior were also found to be similar when compared between O vs WT, O vs HET, and O vs HET + WT groups. The mean number of biologics used between groups was 1.50 (O), 1.39 (HET) and 1.42 (WT) (P = 0.55), with no difference in first or total duration of biologic therapy between groups. 60.8% of O patients used immunomodulators compared to 54.8% of HET and 59.6% of WT patients. In addition, there were no differences in the number of patients who required >1 CD-related hospitalization (O = 30.1%, HET = 34.1%, WT = 30.3%) or surgery (O = 32.2%, HET = 39.5%, WT = 32%) with the entire cohort having a mean of 1.46 for hospitalization and 1.43 for surgery, respectively.

CONCLUSION:
In this single center analysis of 635 patients with Crohn's Disease, FUT2 genotype was not associated with disease phenotype, disease severity, or clinical outcomes. This may be due to the fact that lack of fucosylation is a more of a causative factor but does not contribute to disease progression in CD.
698 Epidemiology and Clinical Outcomes of Microscopic Colitis: Preliminary Results From the Loyola University Microscopic Colitis Registry (LUMiCoR)
Authors: Oruganti Poornima , Awan Rehmat Ullah , Sugimoto Matthew , Ding Xianzhong , Wesolowski Michael , Abegunde Ayokunle T. 
Published: October 2019

INTRODUCTION:
Microscopic colitis (MC) is a common cause of chronic diarrhea with limited long-term data. MC consists of 2 distinct histopathological diagnoses; Lymphocytic colitis (LC) marked by >20 intraepithelial lymphocytes (IELs) per 100 epithelial cells (ECs) and collagenous colitis (CC) characterized by > or < 20 IELs/100 ECs and a thickened subepithelial collagen band (>10 microns). Recently, variant forms with fewer characteristic features have been reported under different names; “incomplete collagenous colitis (CCi)” and “incomplete lymphocytic colitis (LCi)” raising concern that CCi or LCi may represent different manifestations during the disease course or different stages of disease development.

METHODS:
We conducted a natural language search of the pathology records at our institution from 2008 to 2018 using the words “lymphocytic colitis” and “collagenous colitis.” The total sample included patients with either a diagnosis of MC or MCi (CCi/LCi). Chart review was performed to obtain data on demographics, comorbidities, medication, diagnosis, treatment and outcomes. Data were analyzed for descriptive statistics. Logistic regression was used to estimate the unadjusted effects of different variables on MC.

RESULTS:
A total of 216 patients (88.32% white, 80.56% females) with mean age 67 ± 16 were studied; 50% had CC, 40.3% had LC and 9.7% had MCi. The majority (52.3%) were smokers and 21.8% of females were using some form of hormonal therapy (Table 1). There was a statistically significant association between the use of tricyclic antidepressants (TCAs) and LC compared with CC (OR 3.23, 95% CI 1.18-8.80, P = 0.02; Table 2). Smoking, statins, aspirin and beta-blockers were significantly associated with CC compared with MCi (all P < 0.05; Table 3); 29 (13.4%) patients with unresolved symptoms underwent repeat colonoscopies with biopsies. One case of MCi resolved, 8 (72.7%) out of 11 cases of LC resolved, 2 (18.2%) continued to be LC and 1 (9.1%) transformed to CC, 8 (47.1%) out of 17 cases of CC resolved, 8 (47.1%) continued to be CC and 1 (5.9%) transformed to LC.

CONCLUSION:
The majority of patients had CC. TCA use was more likely to be associated with LC than CC. MCi was less likely to be associated with smoking and medications compared with CC. Biopsies from repeat colonoscopies in some patients revealed changes in the pathological diagnoses raising the question of interchangeability of MC (CC to LC and vice versa). However, our results need to be prospectively validated in a larger population.
704 Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Ulcerative Colitis: An Interim Analysis of an Open-Label, Long-Term Extension Study With up to 5.5 Years of Treatment
Authors: Lichtenstein Gary R. , Loftus Edward V. , Soonasra Arif , Lawendy Nervin , Chan Gary , Zhang Haiying , Wang Wenjin , Thorpe Andrew J. , Bloom Stuart 
Published: October 2019

INTRODUCTION:
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Tofacitinib safety and efficacy were demonstrated in patients (pts) with moderate to severe UC in 3 Phase 3 studies,
1
and are being evaluated in an ongoing, open-label, long-term extension (OLE) study.
2

METHODS:
We present updated safety and efficacy data from the OCTAVE Open OLE study (NCT01470612; Sep 2018; database not locked)
2
in completers/treatment failures in OCTAVE Sustain (NCT01458574) or non-responders in OCTAVE Induction 1/2 (NCT01465763/NCT01458951). Week (Wk) 8 data (OCTAVE Induction 1/2) and Wk 52 (completers) or early-termination data (OCTAVE Sustain) determined eligibility. Pts in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore 0) at Wk 52 of OCTAVE Sustain (central read) received tofacitinib 5 mg twice daily (BID) in the OLE study; all others received 10 mg BID. At Month 2, all pts had endoscopy, and induction non-responders with no clinical response were withdrawn. Incidence rates (IRs; unique pts with events per 100 pt-years [PY]) for adverse events (AEs) of special interest were calculated. Efficacy endpoints were derived from Mayo score (local read).

RESULTS:
Of 944 pts receiving ≥1 tofacitinib dose (for up to 5.5 years), 175 (18.5%) and 769 (81.5%) received 5 and 10 mg BID, respectively (454 and 1550 PY, respectively). 337 (35.7%) pts discontinued due to insufficient clinical response and 78 (8.3%) due to AEs excl. worsening UC. The most frequent AE class was infections and infestations (52.1%). The most frequent AEs were nasopharyngitis (20.3%) and worsening UC (19.5%). IRs (95% CI) for “Tofacitinib All” were: serious infections 1.61 (1.10, 2.27); herpes zoster (all) 3.35 (2.58, 4.27); major adverse cardiovascular events 0.15 (0.03, 0.44); malignancies excl. non-melanoma skin cancer (NMSC) 0.85 (0.50, 1.36); and NMSC 0.81 (0.46, 1.32), with no clustering of malignancy type. Table 1 shows AEs and IRs by dose. No new safety risks were identified. Table 2 shows efficacy data at Month 36.

CONCLUSION:
In pts with UC in the OLE study, no new safety risks emerged at 5.5 years vs earlier OLE analyses
2
or with tofacitinib in rheumatoid arthritis. Efficacy data continue to support long-term efficacy of tofacitinib 5 or 10 mg BID up to 36 months beyond OCTAVE Sustain.
709 Optimizing the Definition of Clinical Response Using the Modified Mayo Score: An Analysis of a Phase 2 Study With Mirikizumab in Patients With Ulcerative Colitis
Authors: Jairath Vipul , Sandborn William J. , Dong Yan , Naegeli April , Tuttle Jay , Durante Michael , Arora Vipin , D'Haens Geert R. 
Published: October 2019

INTRODUCTION:
The 12-point Mayo Clinic Score (MCS), composed of four domains, has traditionally been used in defining regulatory endpoints for clinical remission in ulcerative colitis (UC) clinical trials. Clinical response has been defined as a reduction in MCS ≥3 points and ≥30 percent decrease from baseline (BL). Recent guidance from the FDA and EMA recommend use of the 9-point Mayo Score (Modified MCS; MMS) and its components for clinical trial endpoints, which excludes the physician's global assessment (PGA) subscore.
1,2
AMAC was a phase 2 randomized trial clinical trial of mirikizumab (miri), a p19-directed IL-23 antibody, in patients with moderate to severely active UC, which defined clinical response as decrease in the MMS of ≥2 points and ≥35% decrease from BL, and a decrease of ≥1 point in the rectal bleeding (RB) subscore from BL, or a RB score of 0 or 1. We performed a post-hoc analysis of AMAC data to demonstrate that given the MMS, a 30% reduction, along with RB reductions, is appropriate to capture improvement.

METHODS:
Contingency table analysis was used to evaluate MCS responders and non-responders by ≥30% and ≥35% MMS. Sensitivity and specificity were used to evaluate a representative percent improvement in MMS clinical response between MCS defined responder and non-responders.

RESULTS:
Using the MMS, removal of the PGA does not change the expected percentage difference from BL for responders compared to MCS when using the 30% clinical response definition. With total MCS as the anchor variable, the accurate classification rate with a ≥30% decrease in MMS is (124 + 110)/249 = 93.9%, and (127 + 104)/249 = 92.8% when using the ≥35% decrease (Table 1). The high classification rates show a very strong consistency between MMS and MCS at both cutoffs; however, sensitivity and specificity appears to be more balanced at a ≥30% decrease cutoff, with the two being close to equal (Figure 1).

CONCLUSION:
The more appropriate definition for identifying patients with UC in clinical response based on the MMS uses the ≥30% decrease from BL cutoff. This definition, along with a decrease of ≥2 points in the MMS from BL and ≥1 point in the RB subscore or a RB score of 0 or 1, is consistent with the prior definition using the total MCS.
711 Comorbidity Burden Among Patients With Ulcerative Colitis in the United States
Authors: Pilon Dominic , Obando Camilo , Ding Zhijie , Voelker Jennifer , Muser Erik , Manceur Ameur M. , Kinkead Frederic , Lafeuille Marie-Hélène , Lefebvre Patrick 
Published: October 2019

INTRODUCTION:
The symptoms and comorbidities associated with ulcerative colitis (UC) add to the disease burden. Long-term assessment of the comorbidities associated with UC is needed. The objective of this study was to evaluate UC-related comorbidities, including opioid use as a proxy for pain diagnosis, among patients in the United States.

METHODS:
This was a retrospective matched cohort study. Working age adults with UC (≥2 independent claims with a UC diagnosis ≥30 days apart and within 1 year; first UC diagnosis was the index date) and controls without diagnosis for inflammatory bowel disease (IBD; random index date) were identified in a US healthcare claims database (OptumHealth Care Solutions, Inc.) of privately-insured patients (01/1999-03/2017). UC patients were matched 1:5 with non-IBD controls using baseline characteristics, including the Quan-Charlson comorbidity index and cardiovascular disease. Comorbidities during the 12-month baseline period before the index date were reported. During the follow-up, the incidence of new comorbidity, including opioid use, was compared to the non-IBD matched controls by Kaplan-Meier (KM) rate with log-rank test.

RESULTS:
There were 9,353 UC patients and 46,765 non-IBD matched patients in the study sample. The average age was 46 years old, and 50% of patients were female. At baseline, the symptoms and comorbidities significantly higher in the UC cohort were pain, fatigue, and anemia (Figure 1). During the follow-up, the rate of new cases of cardiovascular disease was significantly higher in the UC compared to the matched non-IBD cohort, reaching 8.8% vs 7.8% at year 6, respectively (Figure 2). The rates of new cases of fatigue (4.7 vs 3.3%), anemia (4.8 vs 1.8%), respiratory disease (2.9 vs 1.8%), and anxiety (4.1 vs 2.6%) were also significantly higher in the UC cohort compared to the non-IBD cohort by year 6 (P-value < 0.001). Rates of new pain diagnosis or opioid use cases were significantly higher in the UC cohort reaching 70.8% compared to 58.0% in the non-IBD cohort, by year 6 (Figure 3).

CONCLUSION:
In this large retrospective study with long follow-up, comorbidities occurred more frequently in UC compared to matched non-IBD patients. Notably, the rate of new cases of pain/opioid use was significantly higher in UC patients reaching 70.8% by the end of follow-up. These results suggest that patients with UC also have a higher rate of concurrent comorbidities, which add to the disease burden.