bluuebunny/crossref_metadata_2025 huggingface dataset:
661 Isolated Lymphoid Aggregates Identified in Non-Inflammatory Bowel Disease (IBD) Patients Are Associated With an Increased Incidence of IBD Development
Authors: Cholapranee Aurada , Sultan Keith , Pohanka Charles J.
Published: October 2019

INTRODUCTION:

The Centers for Disease Control and Prevention reports an estimated incidence rate of IBD between 17.7-28.9 cases per 100,000 person years. While IBD is typically associated with visible mucosal abnormalities studies have shown that up to 40% of patients with suspected IBD and normal appearing mucosa have evidence of inflammation on biopsy. Lymphoid aggregates (LA) are often found on histopathology in cases of known or suspected IBD, along with more characteristic findings of chronic inflammation, crypt distortion/abscesses. However, the significance of isolated LA without other abnormal histopathology is unknown. We hypothesized that isolated LA may be a marker of future onset IBD.

METHODS:

We conducted a retrospective study using a patient database at the Endoscopy Center of Long Island, part of Northwell Health system. A database query was conducted of all colonoscopy reports for adults > 18 years of age during the years of 2006-2011. These reports were reviewed for associated histopathology reports describing LA. Patient were excluded if the histopathology reported any finding suggestive or diagnostic of IBD other than LA. Only patients with a followup colonoscopy were included in final analysis. Patient medical records were further used to exclude those with a documented IBD history or use of IBD medication. A diagnosis of IBD on follow up colonoscopy was determined by endoscopic and microscopic findings. The primary analysis used exact binomial methods to compute an exact 95% CI for IBD diagnosis incidence rate as compared to the CDC estimated IBD incidence rate.

RESULTS:

39,680 patients had colonoscopies during the study period. Of these, 767 patients had evidence of LA. 539 (1.36%) demonstrated isolated LA without other evidence of inflammation. Of these, 284 met the requirement of a follow up colonoscopy. 165 were excluded due to documented history of IBD, leaving 119 subjects for analysis. Of these, 5 developed IBD. The median time from initial colonoscopy to diagnosis of IBD was 6.29 years. The observed incidence of IBD in our study group was 654 cases per 100,000 person years, compared to the highest CDC estimated US incidence (P < 0.0001).

CONCLUSION:

We found that LA in patients is associated with an over twenty fold increased incidence of IBD, and may be an early sign of the disease. Some IBD therapies may be reasonable in select patients with isolated LA, and clinicians should not be hesitant to repeat colonoscopy in those with isolated LA and ongoing complaints.
668 Immune Checkpoint Inhibitor Related Colitis (ICI-Colitis) in Patients With Preexisting Inflammatory Bowel Disease or Microscopic Colitis
Authors: Sleiman Joseph , Shah Ravi , Wei Wei , Funchain Pauline , Philpott Jessica , Simons-Linares Roberto
Published: October 2019

INTRODUCTION:

Immune checkpoint inhibitors (ICI) have shown efficacy in the treatment of a growing number of cancers resulting in increasing numbers of patients exposed. ICI-related colitis (ICI-colitis) is a common ICI-related adverse event and mimics inflammatory bowel disease (IBD). In this study, we report the rate of colitis in patients with cancer receiving ICI with pre-existing IBD or microscopic colitis (MC).

METHODS:

We retrospectively reviewed 1672 patients who underwent ICI therapy for cancer at a tertiary center since January 2011. We included patients who had a baseline IBD or MC diagnosis. Demographic data, clinical history of IBD, MC, cancer, ICI treatment, colitis events after ICI therapy and overall survival (OS) were analyzed. OS and time to colitis were estimated by Kaplan-Meier method.

RESULTS:

We identified 13 patients who had either IBD or MC. Among 11 IBD patients, 7 (64%) were on chronic therapy. ICIs were mostly PD-1/PD-L1 inhibitors monotherapy (10, 91%). Six (55%) patients developed colitis at a median of 17 (95% CI: 5-NA) weeks after ICI initiation. Imaging and endoscopy were done in 4 (66%) and 3 (50%) of cases, respectively. Ruling out C. difficile infection was performed in 2 (33%) of cases before starting steroid therapy, and laboratory testing (CRP and ESR) was done in 2 (33%) cases. No case had fecal calprotectin, lactoferrin or enteric PCR testing. 4 (80%) and 5 (100%) of 5 patients on steroid regimens had tapers over at least 6 or 4 weeks, respectively. ICIs were resumed in 2 cases. No case diagnosed as IBD flare was re-challenged with ICIs. In contrast, both patients with MC were on chronic treatment with 5-ASA and local steroid. One of the 2 patients with MC developed grade 1 ICI-colitis within 18 weeks and is still receiving ICI therapy. Median follow-up was 25 months (range: 18-29). Median OS was 12 (95% CI: 2-NA) months.

CONCLUSION:

In our cohort 50-55% of patients with preexisting inflammatory conditions of the intestines developed colitis while on ICIs. This proportion is higher than reported rates of ICI-induced colitis, which range from 0.5-20% in the general population, to 5.2-20% among patients with autoimmune disorders. Further studies require clarification of risk and identification of means to modify risk in order to allow these patients to benefit from cancer therapy.
673 The Peripartum Risk of Deep Vein Thrombosis and Pulmonary Embolism in Women With Inflammatory Bowel Disease: A Population-Based Cohort Analysis
Authors: Saxena Akriti , Dalal Rahul S. , Berera Shivali , Lichtenstein Gary R.
Published: October 2019

INTRODUCTION:

Population-based adverse outcomes in the peripartum period are limited. Both Inflammatory Bowel Disease (IBD) and pregnancy are known risk factors for venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE). The aim of our study was to determine whether the odds of VTE are higher in women with Ulcerative Colitis (UC) and Crohn's disease (CD) at the time of delivery, compared to pregnant patients without IBD.

METHODS:

We performed a population-based retrospective cohort study using the Healthcare Cost and Utilization Project (HCUP)'s Nationwide Inpatient Sample (NIS) between 2005 and 2014. ICD-9-CM diagnosis and procedure codes were used to identify unique obstetric hospitalizations associated with delivery of an infant, and VTE. We created national estimates using appropriate weights for each NIS admission. Multivariable logistic regression was used to evaluate the association of UC and CD with VTE, while adjusting for age, race, smoking, obesity, Charlson Comorbidity Index, chronic steroid use, income, primary insurance, hospital region, and hospital bed size.

RESULTS:

The cohort comprised of 39.8 million deliveries, including 19,167 in women with UC and 31,083 in women with CD. Table 1 depicts baseline characteristics of the cohort. Overall, IBD patients were more likely to be white, have private insurance, receive care at larger hospitals, have a cesarean section and use chronic steroids compared to non-IBD patients. There were 19 (0.1%) cases of VTE in UC patients, 18 (0.06%) in CD patients versus 11,935 (0.03%) in non-IBD patients. Unadjusted odds ratios [OR] were 4.0 for UC; 95% confidence interval [CI] 1.5-10.5, and 2.5 (95% CI, 0.9-6.8) for CD. After adjusting for confounders, the OR for developing VTE was 1.63 (95% CI 0.41-6.55) among UC patients and 2.11 (95% CI, 0.79-5.64) in CD patients. As seen in Table 2, the following variables were associated independently with an increased risk for VTE: age, higher comorbidity scores, inpatient cesarean delivery, obesity and smoking.

CONCLUSION:

Our study showed that patients with IBD were not at greater risk for VTE at the time of delivery compared with non-IBD, perhaps due to the lower absolute risk of VTE over time (0.06-0.1% in our study vs 1.5-2.1% in the 2005 NIS database). Improved awareness and practices surrounding DVT prophylaxis may also be contributing. This study was not able to differentiate between active versus quiescent disease.
679 Epidemiology and Impact of Pneumocystis jirovecii Pneumonia in Hospitalized Patients With Inflammatory Bowel Disease
Authors: Shah-Khan Sardar M. , Shah-Khan Musa , Kupec Justin T.
Published: October 2019

INTRODUCTION:

Pneumocystis jirovecii pneumonia (PJP) is rare opportunistic infection that is most often associated with human immunodeficiency virus (HIV) but is also a reported complication in patients with inflammatory bowel disease (IBD). Treatment for IBD often include systemic corticosteroids and immunosuppressive agents that render these patients to opportunistic infections. Despite this, prophylaxis against PJP remains a topic of debate among providers with no clear consensus. Furthermore, data regarding the burden of PJP in patients with IBD and its impact on healthcare utilization remains limited. We aim to explore the epidemiology and impact of PJP on outcomes in hospitalized patients with IBD.

METHODS:

We queried the National Inpatient Sample (NIS) for all hospitalizations with a primary or secondary diagnosis of IBD [Crohn's disease (CD) or ulcerative colitis (UC)] with or without a diagnosis of PJP using the International Classification of Diseases 9th Edition Clinical Modification codes from 2003-2014. We conducted a retrospective analysis using SPSS (version 25.0). The primary outcome was in-hospital mortality and secondary outcomes included length of stay (LOS) and average total hospital charges. Associations were assessed using multivariable adjustment accounting for age, sex, income, region, hospital characteristics and the Elixhauser comorbidity index. Trend analysis was tested using Cochran Armitage trend test.

RESULTS:

From 2003-2014, there were a total of 840 hospitalizations for PJP in patients with IBD. The patients were primarily white (81%), aged between 41-60 (41.8%) and male (63.2%). Patients with PJP had a greater proportion of in-hospital mortality (10.8% vs 1.6%. P < 0.0001) and were more likely to die while hospitalized (OR 6.2, CI 4.8-7.9, P < 0.0001). PJP was associated with increased mean LOS (13 days vs. 6) and greater total hospital charges ($32,716.12 vs. $14,329.83). Patients with PJP had greater rates of comorbid HIV infection (36.4% vs. 0.30%) and comorbid HIV was associated with a significant risk of PJP infection (OR 232, CI 192-280, P < 0.0001). Cochran-Armitage test did not show a statistically significant increase in the disease incidence over the study period (P = 0.580).

CONCLUSION:

The incidence of PJP in hospitalized IBD patients is low and rates of disease remain stable. Disease is most likely related to comorbid HIV. Overall, PJP in IBD patients is associated with great mortality risk and significantly higher healthcare utilization costs.
686 Neither Obesity nor Hepatic Steatosis Are Associated With an Increased Prevalent or Incident Colonic Dysplasia in Patients With Inflammatory Bowel Disease and Concomitant Primary Sclerosing Cholangitis
Authors: Senter-Zapata Michael , McHenry Scott , Motowski Hayley , Ciorba Matthew A. , Deepak Parakkal
Published: October 2019

INTRODUCTION:

A concomitant diagnosis of Primary Sclerosing Cholangitis (PSC) in patients with Inflammatory Bowel Disease (IBD) is associated with an increased risk of colonic dysplasia. Obesity and hepatic steatosis also have been associated with an increased risk of colonic dysplasia in non-IBD patients. Given the increasing prevalence of obesity in patients with IBD, we aimed to clarify if hepatic steatosis and obesity function as additional risk factors for PSC-associated colonic dysplasia.

METHODS:

This is a single-center, retrospective cohort study between 1/1/2013 through 12/1/2018. Adult patients with a clinical diagnosis of IBD and PSC that had undergone magnetic resonance cholangiopancreatography (MRCP) were included. Those with an alternative etiology of liver disease (e.g., chronic viral hepatitis, greater than moderate alcohol usage) were excluded. MRCP protocols had been modified to allow liver fat quantification by the MR-proton density fat fraction method. Hepatic steatosis was defined as >5.5% liver fat with obesity defined as body mass index (BMI) >30 kg/m2. Prevalent and incident colonic dysplasia were identified. The co-primary outcomes were the Odds Ratio (OR) for the association between hepatic steatosis or obesity and life-time prevalence of colonic dysplasia. Secondary outcomes included the analogous Hazards Ratio (HR) by a cox-proportional hazards model of colonic-dysplasia free-survival from the time of PSC diagnosis.

RESULTS:

112 PSC-IBD patients (80% Ulcerative Colitis, median age at enrollment 48 years, median age at PSC diagnosis 39 years, median BMI 27 kg/m2) had a life-time prevalence of colonic dysplasia in 24 (21%), hepatic steatosis in 22 (20%) and obesity in 23 (21%). Neither hepatic steatosis (OR, 0.8; 95% CI, 0.2-2.6; P = 0.78) nor obesity (OR, 1.1; 95% CI, 0.4–2.9; P = 0.90) were risk factors for the life-time prevalence of colonic dysplasia. Similarly, neither hepatic steatosis (HR, 0.9; 95% CI, 0.3-2.3; P = 0.78) nor obesity (HR, 1.0; 95% CI, 0.9–1.0; P = 0.37), were risk factors for dysplasia-free survival.

CONCLUSION:

We found that hepatic steatosis and obesity were not associated with increased lifetime prevalence for colonic dysplasia in patients with IBD-PSC. This may imply a different pathway for carcinogenesis in IBD-PSC compared to non-IBD patients.
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.
715 Corticosteroid Sparing Effects of Ustekinumab Therapy in UC Patients: Results From the UNIFI Program
Authors: Danese Silvio , Sands Bruce E. , Peyrin-Biroulet Laurent , Marano Colleen , O'Brien Christopher , Zhang Hongyan , Oortwijn Alessandra , Rowbotham David , Leong Rupert W.L. , Arasaradnam Ramesh P. , Van Assche Gert , Sandborn William J. , Panaccione Remo
Published: October 2019

INTRODUCTION:

Ustekinumab (UST), an IL12/23 blocker approved for Crohn's disease, was effective in Phase 3 induction and maintenance studies of patients with moderate-severe ulcerative colitis (UC). Since discontinuation of corticosteroids (CS) is an important goal of therapy in UC, this analysis aims to further describe the CS sparing effects of ustekinumab treatment through Week 44 of the UNIFI trial.

METHODS:

Responders to UST IV induction entered maintenance and were randomized to UST 90 mg SC (q12wks or q8wks), or PBO. During the induction and maintenance studies, oral CS were not to be initiated or increased beyond baseline. At Week 0 of the maintenance study, a scheduled taper was recommended for all patients receiving CS. CS-free Clinical Response (CSR) and remission (CSRem) rates (at Week 44, and for >90 days prior to Week 44) were calculated for the overall population and for the subset of patients on CS at maintenance baseline. Among the subset of patients on CS at maintenance baseline, the mean prednisone-equivalent (P.Eq) CS dose (mg/day) through Week 44 were calculated as were the rates of subjects who were CS-free at Week 44 and for >90 days prior to Week 44.

RESULTS:

Overall 50.6% (265/523) of patients in the primary analysis population were receiving CS at maintenance baseline. The proportions of patients who were receiving concomitant CS at maintenance baseline were 52.3%, 47.7%, and 52.3% in the UST q8w, UST q12w and PBO groups, respectively. As detailed in Table 1, in the overall population, CSR and CSRem rates were significantly higher for patients who continued on UST therapy during maintenance compared with placebo. Among the patients who achieved CSR or CSRem at Week 44, the majority achieved these endpoints and eliminated CS use at or up to 90 days prior to Week 44. Similar results were observed in the subset of patients on concomitant CS at maintenance BL. In this group, the mean daily P.Eq CS dose at maintenance BL was approximately 15.0 mg/day for all treatment groups. Mean decrease in average daily P.Eq dose at Wk 44 was more pronounced and the proportion of patients who were CS-free was greater in the UST maintenance arms.

CONCLUSION:

UST maintenance therapy, with both q8w and q12w dosing regimens, is effective in reducing and eliminating the use of CS in patients with UC; the majority of patients (>90%) who achieved clinical response or clinical remission were able to eliminate corticosteroids.
716 Early Clinical Response and Remission With Vedolizumab Versus Adalimumab in Ulcerative Colitis: Results From VARSITY
Authors: Danese Silvio , Loftus Edward V. , Colombel Jean-Frédéric , Peyrin-Biroulet Laurent , Abhyankar Brihad , Chen Jingjing , Rogers Raquel , Lirio Richard A. , Bornstein Jeffrey D. , Schreiber Stefan , Sands Bruce E.
Published: October 2019

INTRODUCTION:

VARSITY is the first head-to-head trial comparing the efficacy and safety of 2 biologic therapies, vedolizumab (VDZ) and adalimumab (ADA), in patients with moderately to severely active ulcerative colitis (UC). We previously reported significantly higher rates of clinical remission (31.3% vs 22.5%; P = 0.0061) and endoscopic improvement (39.7% vs 27.7%; P = 0.0005) at Week (Wk) 52 with VDZ vs ADA.
1

METHODS:

VARSITY was a phase 3b, randomized, double-blind, double-dummy, active-controlled study (NCT02497469; EudraCT 2015-000939-33). Here we report the predefined, exploratory endpoints of early clinical response and clinical remission (defined in the Table 1) within the first 14 wks, as well as durable clinical remission (patients in clinical remission at Wk 14 and Wk 52).

RESULTS:

A total of 769 patients received ≥1 dose of VDZ (n = 383) or ADA (n = 386). Baseline characteristics were comparable between the 2 groups. A trend for separation in clinical response started to emerge at Wk 6 favoring VDZ vs ADA. Clinical response at Wk 14 favored VDZ vs ADA (257 [67.1%] vs 177 [45.9%]; treatment difference 21.2%). More patients achieved clinical remission at Wk 14 on VDZ vs ADA (102 [26.6%] vs 82 [21.2%]; treatment difference 5.3%). Patients on VDZ achieved higher rates of durable clinical remission (70 [18.3%] vs 46 [11.9%]); laboratory results correlated with these findings. Post hoc analyses showed a larger mean (standard deviation) change of C-reactive protein (CRP) from baseline to Wk 14 (−32.88 [155.77] nmol/L VDZ vs −3.35 [260.81] nmol/L ADA) and to Wk 52 (−50.87 [174.76] nmol/L VDZ vs −37.21 [169.17] nmol/L ADA) in favor of VDZ. Greater mean declines in fecal calprotectin (FCP) levels were seen in patients on VDZ compared with ADA (Wk 14: −1,551.3 [6,236.70] mg/kg VDZ vs −1,167.6 [4,647.67] mg/kg ADA; Wk 52: −2,187.3 [7,440.42] mg/kg VDZ vs −1,846.6 [4,560.55] mg/kg ADA).

CONCLUSION:

Patients on VDZ had numerically higher rates of both clinical response and clinical remission by Wk 14 compared with ADA. Patients on VDZ also achieved higher rates of durable clinical remission compared with ADA. CRP and FCP results correlated with these findings. These data on early clinical response and clinical remission, as well as durable remission, further support the use of VDZ over ADA in patients with moderately to severely active UC.
717 The Vedolizumab Pregnancy Exposure Registry: An OTIS Pregnancy Study Update
Authors: Chambers Christina , Adams Jane , Johnson Diana , Xu Ronghui , Luo Yunjun , Lyons-Jones Kenneth
Published: October 2019

INTRODUCTION:

Vedolizumab is a gut-selective immunoglobulin (Ig) G1 monoclonal antibody that binds to α4β7 integrin; it is approved for the treatment of moderately to severely active Crohn's disease (CD) and ulcerative colitis (UC) in the U.S. and elsewhere. Published studies on the effect of vedolizumab during human pregnancy are limited. Data from the ongoing Vedolizumab Pregnancy Exposure Registry (NCT02678052) in the U.S. and Canada have been collected by the MotherToBaby Pregnancy Studies conducted by the Organization of Teratology Information Specialists (OTIS). This prospective observational cohort study intends to enroll and analyze the outcomes of 100 vedolizumab-exposed participants compared to 100 disease-matched (DM) comparison and 100 healthy comparison (HC) participants. This abstract describes progress of the study through March 1, 2019.

METHODS:

Pregnant women treated with vedolizumab for UC or CD for at least some part of the first trimester were enrolled in the vedolizumab-exposed group. Pregnant women with no exposure to vedolizumab were enrolled in a DM comparison group. Pregnant women with no exposure to any biologic during pregnancy and not diagnosed with an autoimmune disease or any other disease as defined by the OTIS Research Center were enrolled in a HC group. Pregnancy exposure and outcome data were collected from telephone interviews and medical records. The Short Quality of Life in Inflammatory Bowel Disease Questionnaire (SIBDQ) was administered to women with CD or UC at enrollment and 32 weeks' gestation. Follow-up of live born children included a dysmorphological exam, pediatric records review and developmental screening at one year of age.

RESULTS:

Between December 2015 and March 2019, outcomes were collected for 223 women, 53 in the vedolizumab group, 88 in the DM group, and 82 in the HC group. Preliminary descriptive data are shown in Table 1. No major structural birth defects were reported in the vedolizumab group, compared to 5 (5.7%) in the DM group, and 4 (5.3%) in the HC group. There was no evidence of a pattern of minor structural defects in the vedolizumab group.

CONCLUSION:

Updated data indicate pregnant women treated with vedolizumab in at least the 1st trimester have similar birth outcomes to disease-matched and healthy comparison women. The Vedolizumab Pregnancy Exposure Registry is ongoing with formal statistical analysis to be performed when the study is completed.
720 Does Undetectable Absolute Eosinophil Count at Initial Clostridioides difficile Infection Predict Future Disease in Inflammatory Bowel Disease Patients?
Authors: Dickson Zachary , Baray Merwise , Hunold Thomas , Hays R. Ann
Published: October 2019

INTRODUCTION:

According to a 2018 study, an undetectable absolute eosinophil count at the time of admission for Clostridioides difficile infection (CDI) is associated with an increased risk for vasopressor requirement, emergency colectomy, and mortality during the index hospitalization. Patients with inflammatory bowel disease (IBD) are at greater risk for development of CDI than the general population. We aim to investigate whether an undetectable absolute eosinophil count at the time of an initial CDI can be used to predict recurrence versus reinfection of CDI in IBD patients.

METHODS:

A retrospective cohort of patients age 18-75 with a history of IBD and a diagnosis of CDI from January 2012–December 2016. The absolute eosinophil count at the time of initial CDI for patients with a history of single CDI and multiple CDIs was recorded. Absolute eosinophil counts were grouped as either detectable (>0.0 cells/mL) or undetectable (0.0 cells/mL). Recurrence was defined as CDI diagnosis within 3 months of the initial CDI. Reinfection was defined as a second episode of CDI between 3 months to 3 years of the initial CDI. Data was analyzed with chi square tests.

RESULTS:

62 of 121 IBD subjects with CDI had a documented absolute eosinophil count at the time of their initial CDI. Absolute eosinophil count was undetectable in 15 of 62 patients (24.2%). Of these, 67% (n = 10) experienced multiple CDIs. 4 patients had recurrent CDI and 6 patients had CDI reinfections. 27 (43.5%) patients had history of a single CDI and 35 (56.5%) patients had a history of multiple CDI. An undetectable eosinophil count was observed in 18.5% (n = 5) of patients with a single CDI and 28.5% (n = 10) of patients with a history of multiple CDI. Of the 47 patients with a detectable eosinophil count, 22 patients experienced a single CDI vs 25 patients with multiple CDI.

CONCLUSION:

In patients with a peripheral eosinopenia, insufficient IL-25 mediated immunity can predispose patients to development of CDI. Although the absolute eosinophil count at the time of CDI may have implications for inpatient morbidity and mortality in the general population, our study suggests that an undetectable absolute eosinophil count at the time of initial CDI does not reliably predict future acquisition of CDI in IBD patients. However, based on the observation that patients with an initial undetectable eosinophil count more frequently experienced multiple CDIs, it is possible that a significant relationship could manifest with a larger study population.