bluuebunny/crossref_metadata_2025 huggingface dataset:
802 Risk Factors for 90-Day Readmission Among Hospitalized Patients With Ulcerative Colitis
Authors: Goens Donald , Dwadasi Sujaata , Paknikar Raghavendra , Zafer Maryam , Rubin David T. , Micic Dejan
Published: October 2019

INTRODUCTION:

The hospitalization of a patient with an ulcerative colitis (UC) flare reflects a severe disease state and is a significant contributor to the overall costs of care. Thus, understanding which factors influence the likelihood of readmission among patients hospitalized for UC is critical to providing high quality, low cost care. This study aims to evaluate which factors for patients admitted with UC are associated with an increased risk for 90-day readmission.

METHODS:

We designed a retrospective study including all patients 18 years or older with an admission for ulcerative colitis at the University of Chicago Medical Center between 1/1/2013 and 4/1/2018. Cases of ulcerative colitis were identified using the ICD-9 code 556.X and ICD-10 code K51.X and separately reviewed based on clinical, radiographic, histologic and endoscopic information. Data was analyzed using a Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for categorical variables. Multivariate logistic regression was performed to identify independent risk factors for 90-day readmission.

RESULTS:

1,455 admissions were reviewed. 1,046 were excluded for age < 18 (n = 102), diagnosis of Crohn’s disease (n = 42), colitis other than UC (n = 13), history of colectomy (n = 245), admissions unrelated to a UC flare (n = 430), planned surgical procedures (n = 199) and other (i.e. duplicate records, leaving against medical advice; n = 19). An additional 149 were removed for being rehospitalizations (n = 103), absence of 90 day follow up (n = 42). Of the 260 patients remaining, 48 patients (18%) were re-admitted to the hospital within 90 days. Factors associated with re-admission on univariate analysis included: history of parenteral nutrition use prior to colectomy (17.1% vs 6.2%, P = 0.036), use of steroids as an outpatient prior to admission (77.1% vs 57.1%, P = 0.013), and mean units of blood transfused during hospitalization (0.46 vs 0.25, P = 0.006). After controlling for factors in univariate analysis, only outpatient steroid use prior to admission was associated with increased risk of 90-day readmission (OR 3.52; 95% CI 1.32-9.33) (Table 1).

CONCLUSION:

Of the factors studied, only steroid use prior to admission was an independent risk factor for readmission. Additional factors related to readmission risk throughout the hospitalization to include laboratory and vital sign trends may offer additional insights into the risk of readmission.
803 The Majority of Patients With Inflammatory Bowel Disease Are Interested in Drug Discontinuation Despite Risks
Authors: Harrison Nicole , McCarthy John , Singla Manish
Published: October 2019

INTRODUCTION:

Inflammatory bowel disease (IBD) is a chronic autoimmune condition affecting the gastrointestinal tract. Advances in immunosuppression have led to high rates of remission; discontinuation of immunosuppression is associated with a 50% risk of relapse within 2 years. The aim of this study is to determine whether patients would be interested in drug discontinuation despite this risk of relapse.

METHODS:

This is a retrospective study of patients in our IBD clinic in clinical remission for greater than a year with no signs of ongoing inflammation that were counseled on immunosuppression discontinuation and the risks therein. We examined the electronic health record for their age, duration of disease, disease phenotype and severity, duration of therapy, and disease characteristics (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fecal calprotectin, endoscopy) at time of discussion. All patients were counseled by one of two IBD specialists of a 50% risk of flare within 2 years with a 80-90% chance of recapture with the same agent that was discontinued. Decisions about which patients to offer discontinuation were at the discretion of the provider. Patients who self-elected to discontinue drugs were excluded from the study.

RESULTS:

40 patients were counseled on drug discontinuation. Average age was 50.0 ± 15.0 years. Patients had an average of 15.5 ± 9.9 years of disease, and 6.1 ± 5.0 years of the therapy that was discussed for discontinuation. 39 patients (98%) wanted to discontinue drugs. 20 discontinued 6-mercaptopurine, 8 patients discontinued methotrexate, 4 patients discontinued azathioprine, 3 patients discontinued adalimumab, and 3 patients discontinued infliximab. At time of discontinuation, patients had a mean ESR of 19.3 ± 13.0 mm/hr, and a mean CRP 0.30 ± 0.54 mg/dL. After a mean 29.0 ± 16.8 months of follow up, four patients had clinically flared and were placed back on immunosuppression. The remaining 36 patients had a follow up mean ESR 20.1 ± 14.8 mm/hr and CRP 0.27 ± 0.32 mg/dL.

CONCLUSION:

Patients with IBD are overwhelmingly interested in drug discontinuation, with >95% of patients offered discontinuation choosing to do it. In carefully selected patients, discontinuation is safe and well tolerated, with 90% of patients in biomarker and clinical remission more than 2 years after drug discontinuation.
808 Clinical Course of Patients With Concomitant Eosinophilic Esophagitis and Inflammatory Bowel Disease
Authors: Leung David , Nhu Quan M. , Konijeti Gauree G.
Published: October 2019

INTRODUCTION:

An overlap between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD), both immune-mediated diseases of the gastrointestinal tract, is gaining recognition. However, the natural history and clinical implications of concurrent EoE and IBD remain to be characterized. We describe an institutional experience of patients with concurrent EoE and IBD.

METHODS:

We conducted a retrospective single-center case series of patients with diagnoses of EoE and either Crohn’s disease (CD) or ulcerative colitis (UC) seen between 01/01/2008 and 12/01/2018. Clinical data were analyzed for demographics, diagnostic findings, medical treatments, and disease outcomes.

RESULTS:

In our cohort, the prevalence (per 100,000 patients) of EoE, CD, and UC was 58.9, 111.4, 159.5, respectively. We identified 7 patients with both IBD (4 CD, 3 UC) and EoE. All were Caucasian, with median age 52 (SD 15.9), and 86% male. Median age at diagnosis of IBD was 25.5 (SD 17.4), and EoE was 50 (SD 15.9). Diagnosis of IBD preceded EoE in 6/7 patients, by an average of 14.3 years (range, 2-30 years). At the time of EoE diagnosis, IBD therapies included no therapy (29%), mesalamine (29%), ustekinumab (14%), or adalimumab/6-mercaptopurine (14%). EoE was treated with proton-pump inhibitor (PPI) in 4 patients (43%), elimination diet in 2 (29%), and/or swallowed fluticasone in 1 (14%). EoE complications, identified at time of EoE diagnosis, included 2/7 (29%) requiring esophageal stricture dilation. No further EoE complications developed following EoE treatment. CD complications preceded diagnosis of EoE, with 2 patients with perianal fistula, one with both ileal stricture and perianal fistula. No UC-associated or additional CD complications were identified after EoE diagnosis. Co-existing immune-mediated conditions included allergic rhinitis (43%), primary sclerosing cholangitis (14%), and rheumatoid arthritis (14%).

CONCLUSION:

In our cohort, diagnosis of IBD preceded EoE diagnosis by more than one decade, with EoE median age at diagnosis occurring later in IBD than that reported in non-IBD patients. Majority of disease-related complications in either IBD or EoE appear unrelated to concomitant diagnosis or treatment. Further studies are needed to examine immune-mediated pathways resulting in these concomitant diagnoses
811 Ustekinumab for Concomitant Crohn’s Disease and Psoriasis
Authors: Rehman Saif U. , Farooq Umer , Amin Muhammad K. , Ahmed Zahoor , Bakhat Khush , Riaz Asma , Gondal Amlish B.
Published: October 2019

INTRODUCTION:

Ustekinumab (CNTO 1275), approved for Crohn’s disease (CD) and psoriasis, acts by preventing the immune responses involved in the pathogenesis of CD and psoriasis. It is an IgG1 monoclonal antibody that blocks the activation of IL-12 and IL-23 by binding to their P40 subunits. The scope of this systematic review was to review the clinical effectiveness of Ustekinumab in the treatment of patients who have a concomitant diagnosis of CD and psoriasis.

METHODS:

A systematic literature search was conducted using MeSh terms on MEDLINE per PRISMA reporting guidelines. Following the PICO framework, research articles with patients having a concomitant diagnosis of Crohn’s disease and psoriasis, treated with Ustekinumab were included. Psoriatic subjects with CD were included, regardless of whether their psoriasis was primary or anti-TNF therapy induced. Study designs included were retrospective cohorts, prospective cohorts, clinical trials, case reports and case series due to the anticipated paucity of literature on the study topic. Studies on non-human subjects and not in English were excluded.

RESULTS:

Of the 45 studies identified by systematic searches, 8 studies (n = 206) met the inclusion criteria (Figure 1). Seventy five percent patients had concurrent CD and treatment induced psoriasis whereas the rest had concurrent CD and primary psoriasis. Inductions doses of Ustekinumab ranged from 45 mg to 90 mg subcutaneously; maintenance doses were 45 to 90 mg after every 12 weeks, subcutaneously. In this patient population with concomitant CD and psoriasis (Table 1), Ustekinumab was reported to be efficacious for treatment of CD, reducing Crohn’s disease activity index (CDAI) and Harvey Bradshaw index scores, while demonstrating improvement in clinical symptoms and ileocolonoscopy findings. Similarly, improvement in psoriasis was reported by reductions in psoriasis area and severity index (PASI) and clinical assessments of disease severity.

CONCLUSION:

Ustekinumab appears to be novel drug for the treatment of concurrent Crohn’s disease and psoriasis. However, the published literature is limited by its retrospective nature and the extremely limited availability of epidemiologic data for patients with concurrent Crohn’s and psoriasis. Considering the shared immuno-pathogenetic mechanisms governing CD and psoriasis, further investigation is needed on studying the efficacy and adverse effects of ustekinumab.
812 Change in Medical Expenses Per Capita for Inflammatory Bowel Disease in Korea Over the Last Five Years
Authors: Jung Sung Hoon , Kang Sang-Bum , Kim Dae Bum
Published: October 2019

INTRODUCTION:

As the incidence of IBD has increased, the overall cost of medical care also has been increasing. However, It is not clear whether the per-capita cost is increasing or not in the era of biologics. We aimed to estimate annual per-capita health care expenditures for IBD and analyze the trends by region and age in Korea overall the last five years.

METHODS:

We estimated IBD patient data and reimbursement information from the Korean Health Insurance Review & Assessment Service between 2013 and 2017. The data converted into the annual per capita healthcare expenditures were analyzed by region and age. For analysis of the results, the currency unit is KRW1000. (KRW1000 = USD0.9).

RESULTS:

The overall number of IBD patient has increased steadily (CD;16,138 & UC;31,026 in 2013 vs CD;20,231 & UC;40,939 in 2017), and the overall cost of medical care has also increased significantly. The annual per capita healthcare costs for CD and UC have also increased steadily since 2013 and nearly doubled in 2017(CD;3583.03 & UC;999.48 in 2013 vs CD;6134.04 & UC;1651.68 in 2017). The annual per capita healthcare costs for CD and UC in major cities including Seoul, where Tertiary referred hospitals are located, was higher than that for other regions (Figure 1). The annual per capita healthcare costs for CD in teens, 20s and 30s was higher than other decades and then decreased sharply, and that for UC in teens and 20s was high and then gradually decreased (Figure 2). Interestingly, the annual per capita healthcare costs for girls under the age of 10 in UC has increased dramatically.

CONCLUSION:

The health-care cost in IBD has been increasing not only on a whole scale but also on a per capita healthcare costs in Korea over the last five years. Consuming more medical costs at younger ages means that they are suffering from moderate-to-severe disease, which means that there is a large socio-economic loss. Given the increasing trend, government measures are needed to support medical expenses in the future, and it is thought that a sustained trend analysis is needed.
814 Characteristics of Microscopic Colitis (MC) in a Diverse Urban Healthcare Setting
Authors: Hong Simon , Patel Sneha , Panarelli Nicole , Brandt Lawrence
Published: October 2019

INTRODUCTION:

MC is a chronic inflammatory condition of the colon characterized by watery, non-bloody diarrhea and is comprised of 2 subtypes: collagenous colitis (CC) and lymphocytic colitis (LC). Prior population-based studies of MC have been performed in regions such as Northern Europe and Olmsted County, MN which, in general, are racially homogenous. The purpose of our study is to describe the characteristics of patients (pts) with MC in a diverse, urban medical center in Bronx County, NY.

METHODS:

We retrospectively identified pts diagnosed with MC between January 2006 and June 2018 at our institution. Diagnosis was confirmed based on chart review of pts’ symptoms and histopathology. For each patient (pt), we recorded demographics, disease characteristics and co-morbidities. Our population characteristics were compared with those reported for pts with MC in Olmsted County, MN (Gentile et al. 2014).

RESULTS:

76 pts were included in our study. The median age at diagnosis was 61.5 years (range 31 to 89 years) and 55 (72.4%) were female. There was a slight predominance of CC over LC (52.6% vs. 47.4%), with a trend towards significance compared with pts in Olmsted County, where CC was less common than LC (42.9% vs 57.1%, P = 0.10) (Table 1). Pts in Bronx County had lower rates of smoking (27.5% vs 52.5%, P < 0.01), but similar rates of autoimmune disease (21.4% vs. 19.2%, P = 0.75) compared with pts in Olmsted County. Race/ethnicity was reported in 65 pts, of whom 34 (52%) were Caucasian, 7 (11%) were African-American (AA), and 24 (37%) were Hispanic. When comparing pts based on race/ethnicity, AA and Hispanic pts were younger (P = 0.02) and had lower socioeconomic status (SES) (P < 0.01) than Caucasian pts (Table 2). No statistically significant differences in sex or MC subtype were seen among the 3 racial/ethnic groups.

CONCLUSION:

The racially/ethnically mixed pt population with MC in our urban healthcare setting has more CC predominance and less smoking exposure compared with the predominantly Caucasian population in a previously described US cohort. Age at diagnosis, female predominance and rates of concurrent autoimmune disease are similar. AA and Hispanic pts have an earlier age at diagnosis and lower SES than Caucasian pts. Our findings suggest that a diverse population may have a different presentation of MC than previously described. Larger population-based studies in these communities are needed to confirm our findings.
816 The Prevalence and Clinical Associations of Sacroiliitis in Crohn’s Disease Using a Standardized Magnetic Resonance Scoring System
Authors: Levine Irving , Malik Fardina , Castillo Gabriel , Jaros Brian D. , Alaia Erin , Ream Justin , Scher Jose U. , Hudesman David P. , Axelrad Jordan E.
Published: October 2019

INTRODUCTION:

Sacroiliitis (SI), an inflammatory arthropathy of the sacroiliac joints, has an established correlation with Inflammatory Bowel Disease (IBD). Yet SI often goes undiagnosed, and the clinical association between IBD disease activity and SI is not established. Patients with Crohn’s disease (CD) often receive magnetic resonance enterography (MRE), affording clinicians the opportunity to evaluate for the presence of sacroiliitis. We sought to identify the prevalence and disease characteristics associated with SI in CD using MRE.

METHODS:

All CD patients undergoing MRE for any reason between 2014-2018 at an IBD referral center were identified. A musculoskeletal radiologist reviewed all MRE exams for acute and chronic SI using standardized scoring. We analyzed demographics, IBD characteristics, clinical and endoscopic activity, and management between CD patients with and without SI.

RESULTS:

258 patients with CD underwent MRE during the study period. The mean age was 35 years old, 53% were male, and mean duration of CD at MRE was 9 years. Few reported back pain (8%) and 14% had previously seen a rheumatologist. Overall, 17% (n = 45) of patients had MR evidence of SI (Table 1). Female gender, back pain, and later age of CD diagnosis were associated with SI (P = 0.05, P < 0.001; P = 0.04 respectively; Table 2). Disease location and medication exposures were not associated with SI. Stricturing phenotype was associated with a lower rate of SI (7%) compared to inflammatory (48%) or penetrating phenotypes (45%). Disease activity, noted by clinical scores, endoscopic disease activity, or radiographic disease activity, were not associated with SI (Table 2). On multivariable analysis, only back pain was associated with SI (OR 3.01, 95% CI; P = 0.04).

CONCLUSION:

SI is a common comorbid condition in CD, but often underdiagnosed. With limited clinical clues and disease characteristics to suggest SI, physicians may utilize MRE for clinical activity to assess for SI. Data suggest targeted screening of patients with back pain.
819 Comparing Efficacy and Adverse Effects of Biological Agents in South Asian Inflammatory Bowel Disease Patients Living in the United States to Caucasian American Patients
Authors: Bodiwala Vimal , Marhsall Timothy , Seril Darren
Published: October 2019

INTRODUCTION:

The aim of this study was to compare the efficacy and adverse effects of biological therapies in South Asian patients with Crohn’s disease (CD) and ulcerative colitis (UC) living in the United States with those of a Caucasian American cohort.

METHODS:

The efficacy, reasons for therapy discontinuation, and adverse effects of biological therapies in 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive Caucasian American patients (245 CD and 163 UC). The reasons for biologic therapy discontinuation were classified as: financial barrier, clinician judgment based on disease remission, primary non-response, secondary non-response, adverse effects, and patient preference. Adverse effects for biologic agents were classified as injection site reaction, infusion reactions, cytopenia, secondary infections, neurologic effects (including demyelinating disease or vestibular issues), cardiac effects (including heart failure), cutaneous effects, malignancy, and others.

RESULTS:

For both the South Asian and Caucasian American cohorts, adalimumab and infliximab were the most commonly prescribed biologic agents. Twenty-two out of 22 (100%) South Asian CD patients treated with adalimumab or infliximab had primary response. The Caucasian American CD cohort had a primary non-response rate of 16.5% to adalimumab and 12.1% to infliximab (Table 1). There was no statistical difference noted in the incidence of secondary non-response due to immunogenicity between South Asian and Caucasian American CD patients. Primary non-response, secondary non-response and adverse effects were the leading reasons for discontinuing biological therapy in both UC cohorts (Table 2). South Asian and Caucasian American CD patients experienced similar rates of adverse effects to anti-TNF therapy (Table 3). South Asian UC patients had a higher rate of primary non-response and a lower rate of adverse events with infliximab therapy compared to Caucasian American UC patients (Table 3).

CONCLUSION:

A cohort of South Asian IBD patients, mainly migrants, showed differing rates of response and adverse effects to biological therapies compared to a Caucasian American cohort. Of note, South Asian CD patients had higher rates of primary response to anti-TNF therapy than Caucasian American CD patients. These results provide insights into ethnic and racial variation in IBD therapeutics.
820 What Can Prealbumin/Albumin Ratio Tell You About Etiology of Hypoalbuminemia?
Authors: Lin Bixuan , Sherman Katherine , Berger William
Published: October 2019

INTRODUCTION:

Hypoalbuminemia can be caused by either decreased albumin production (e.g. malnutrition, systemic inflammation, liver disease) or increased loss (e.g. protein-losing enteropathy, increased metabolism, wounds). Prealbumin is affected by the same factors as albumin, but its half-life of 2 days is a fraction of the 21-day half-life of albumin. Due to this difference in half-life, protein loss should disproportionately impact albumin level, while underproduction should impact both proteins more equally. Therefore, the prealbumin to albumin ratio (PAR) may present a quick, noninvasive, and cost-efficient tool to help elucidate causes of low albumin.

METHODS:

We performed a retrospective chart review of subjects seen at the CJ Zablocki VAMC in Milwaukee, WI, USA between 2012-2016 with albumin and prealbumin levels drawn within 1 week of each other. Chronic kidney disease patients were excluded as prealbumin clearance is impaired in this population. Prealbumin to albumin ratio (PAR) was defined for each category of hypoalbuminemia etiology (loss, underproduction, or mixed) as determined by chart review including notes by physicians and nutritionists, medical history, and labs reflecting nutrition and inflammation (ferritin, CRP, ESR, lymphocyte count). A validation set was then run against these proposed parameters.

RESULTS:

The definition (n = 36) and validation (n = 96) sets did not differ significantly in age, gender, or inpatient status. PAR separated by etiology (Figure 1) shows clear distinction between loss and underproduction. PAR differences are shown in Table 1. A linear progression model comparing PAR in protein loss only (n = 10) versus underproduction only (n = 21) provided a 97% prediction accuracy with r2 of 0.58 when PAR cut-off was set to 6.5.

CONCLUSION:

PAR is significantly higher among individuals with protein loss verses protein underproduction. PAR may be particularly useful as a screening tool for deciding whether to pursue PLE workup in a patient with unexplained hypoalbuminemia. Clinical utility of PAR needs to be further studied and is likely limited to patients with no more than 1 or 2 possible etiologies for hypoalbuminemia.
826 Biologic Use in Pediatric Patients Newly Diagnosed With Crohn’s Disease in the United States, 2010-2013 and 2014-2016
Authors: D'Haens Geert R. , Naegeli April , Mahoui Malika , Morton Stuart , Dong Yan , Hunter Theresa
Published: October 2019

INTRODUCTION:

The purpose of this study is to characterize treatment patterns and sequences of biologic initiation in pediatric patients newly diagnosed with Crohn’s Disease (CD) in the United States in 2010-2013 and 2014-2016.

METHODS:

Pediatric (0-17 years) patients with ≥2 CD diagnosis codes (ICD-9: 555.x; ICD-10:K50.x) from October 1, 2010 to September 30, 2016 were included in this retrospective analysis of medical and pharmacy claims data from the IBM Marketscan Commercial and Medicaid Claims database. Patients were excluded if they were >18 years old, had an Ulcerative Colitis (UC) diagnosis, had a dual UC and CD diagnosis, or did not have treatment throughout the study period. Pathway visualization techniques and subgroups analyses were conducted for the 2 years post diagnosis to compare biologic use following first diagnosis during 2010-2013 and 2014-2016. Two-sample t test were conducted for continuous patient characteristics between 2010 -2013 and 2014-2016 diagnosis periods. Chi-square tests were used to compare categorical variables.

RESULTS:

A cohort of 940 CD patients were identified with 482 (51.3%) diagnosed with CD during 2010-13 and 458 (48.7%) diagnosed during 2014-16. The majority of patients during both time periods were male. Mean age at diagnosis was not statistically different during 2010-2013 and 2014-2016 (13.4 vs. 13.5 years; P = 0.75). In general, the majority of patients initiated conventional treatment (aminosalicylates, immunomodulators, and/or corticosteroids) at the time of diagnosis. However, there was a statistically significant increase in biologic use from 43.6% of patients in 2010-2013 to 59.8% of patients in 2014-2016 (P < 0.001). The median time to biologic treatment in the 2 years post diagnosis was 173.0 days for those diagnosed 2010-13 versus 76.5 days for those diagnosed during 2014-16 (P < 0.001). Infliximab was more frequently identified as the first-line biologic in the 2 years post diagnosis for those diagnosed 2010-13 and 2014-2016, yet rates of infliximab were low. However, pathway visualization Sankey diagrams illustrated limited switching from one biologic to another after initiation of biologic therapy during the 2 years post diagnosis for 2010-13 (Figure 1), with no predominant sequence identified. This trend remained for the 2014-16 cohort (Figure 2).

CONCLUSION:

Biologic use among pediatric CD patients has increased in recent years; however conventional treatment is still more common at the time of diagnosis.
827 Efficacy and Safety of Tofacitinib in Moderate-Severe Ulcerative Colitis: A Systematic Review and Meta-Analysis
Authors: Dhindsa Banreet , Dhaliwal Amaninder , Mashiana Harmeet , Choa Jacqueline , Sayles Harlan , Ohning Gordon , Hewlett Alexander , Young Renee , Eichele Derrick
Published: October 2019

INTRODUCTION:

Tofacitinib was FDA approved in 2018 for use in patients with moderate to severe ulcerative colitis (UC). It is an oral inhibitor of Janus-kinase 1-3 and can be used in patients who are naïve or have failed other biological therapies. We conducted a systematic review and meta-analysis to assess the overall clinical response and remission of Tofacitinib in patients with moderate-severe UC.

METHODS:

We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Web of Science databases, Google Scholar and manual search of references (from inception through October 2018) to identify studies that reported use of Tofacitinib in moderate-severe UC patients. The primary outcome was to look at the clinical response and remission and secondary outcome was to look for adverse events. Clinical response was defined as an absolute decrease of Mayo-score by at least 3 points and a relative decrease by at least 30%-with an accompanying decrease in rectal bleeding sub score of at least 1 point or an absolute rectal bleeding sub score of 0 to 1. Clinical remission was defined as total Mayo score of 0 to 2, with no individual sub score exceeding 1. The meta-analysis was performed using Der Simonian and Laird random effect model.

RESULTS:

A total of 6 studies reporting on 1207 patients receiving 10 mg of Tofacitinib were included in our final meta- analysis. The mean age and follow up were 41.5 years and 15.4 months respectively. 497 patients and 627 patients (using 5/6 studies) were TNF inhibitors naïve and experienced respectively. The overall pooled clinical response and clinical remission of Tofacitinib in moderate-severe UC was 59.68% (95% CI = 55.3- 63.57, I2 = 31.92%) and 31.61% (95% CI = 20.78-43.52, I2 = 92.77%) respectively (Tables 1 and 2). The overall adverse events were 706, which mainly included infections with 22.73% [95% CI = 15.51- 30.83, I2 = 86.13%). The cumulative incidence of Herpes zoster was 0.6% (95% CI = 0.0-2.24, I2 = 67.21%). Significant heterogeneity was noted in the studies included in our meta-analysis.

CONCLUSION:

Based on the limited data included in our meta-analysis, Tofacitinib (10 mg) seems to have good overall clinical response rate of 59.68%. There was higher rate of infections noted in our meta-analysis. Overall low incidence of Herpes zoster could be due to short follow up (4/6 studies). Further multi-center studies are needed to assess long-term efficacy and safety of Tofacitinib in moderate-severe ulcerative colitis patients.
829 Appropriateness of Treatment Options in Mild to Moderate Ulcerative Colitis: A RAND Appropriateness Panel
Authors: Irving Peter M. , Melmed Gil Y. , Lightner Amy L. , Kotze Paulo , Ullman Thomas , Raffals Laura E. , Baidoo Leonard , Bressler Brian , Cheifetz Adam , Devlin Shane , Jones Jennifer , Kozuch Patricia , Sparrow Miles , Velayos Fernando , Siegel Corey A.
Published: October 2019

INTRODUCTION:

Treatment options for patients with moderate-severe ulcerative colitis (UC) are increasing. The appropriateness of their use in mild-moderate UC is less clear, as is the role of surgical intervention. Our aim was to define the appropriateness of therapeutic options in a range of clinical scenarios in mild-moderate UC

METHODS:

We applied the RAND/UCLA Appropriateness Method to rate appropriateness of treatment choices in patients with mild-moderate UC; severe disease (likely to need hospitalization or surgery within 2 weeks) was excluded. A literature review was presented to the BRIDGe group, a panel of 13 IBD specialists, as well as 1 external IBD expert and 2 IBD surgical experts. 12 chapters were constructed including failed 5-ASA, steroid or thiopurine therapy, and primary/secondary non-response to biologics or tofacitinib. Scenarios were also divided by disease extent (proctitis vs more extensive) and activity (mild vs moderate) creating 260 scenarios in all. Panellists used a modified Delphi method to anonymously rate the appropriateness of a therapy on a 1-9 scale (1-3 not appropriate, 4-6 uncertain, 7-9 appropriate). Disagreement was assessed using a validated index (DI) and was defined as a DI > 1. The panellists then convened in person to discuss areas of disagreement, followed by a second round of rating. Scenarios rated a median of 7 or higher were deemed appropriate and those rated 3 or lower were deemed inappropriate. Scenarios rated 4-6 were considered uncertain, as were any with a DI > 1

RESULTS:

Appropriateness was agreed in 131 and inappropriateness in 47 scenarios. Greatest disagreement was around the use of thiopurines, but no scenario had a DI > 1. There were 82 scenarios were rated uncertain. Biologics and tofacitinib were more likely to be rated appropriate for treatment resistance and greater disease activity; disease extent less likely to influence decision making. Surgery was felt to be appropriate in 8 scenarios, generally in more extensive and active disease that had failed to respond to medical therapy. Surgery was felt to be inappropriate in 16 scenarios and was uncertain in 24

CONCLUSION:

Although there was little disagreement amongst an expert panel of IBD physicians and surgeons, there remained uncertainty about the use of medical and surgical therapy in nearly one third of situations in patients with mild-moderate UC. These results could be used to guide the design of clinical trials for these patient groups in order to guide best practice.
830 Can CD74 Predict Treatment Response to Anti-TNF Agents in Inflammatory Bowel Disease?
Authors: Farr Laura , Bucala Richard , Moonah Shannon
Published: October 2019

INTRODUCTION:

Anti-TNF treatment, a game changer for inflammatory bowel disease (IBD) therapy, promotes mucosal healing in patients with IBD (1). By poorly understood mechanisms, a considerable amount of IBD patients either do not primarily respond or lose response to anti-TNF agents (2). A recent study identified a strong association between a polymorphism in the CD74 gene and anti-TNF failure in IBD patients (3). This led us to hypothesize that anti-TNF failure is more likely to occur in the setting of defective CD74 signaling.

METHODS:

To test this hypothesis, we used the common DSS-induced colitis mouse model that mimics key immunological and histopathological features of IBD in humans. We studied both normal wild-type (WT) and CD74 deficient mice. Mice were given alternating days of DSS and normal drinking water to allow for partial repair. Anti-TNF antibody at 10 mg/kg was injected one hour prior to oral DSS administration.

RESULTS:

We found that anti-TNF therapy did not protect CD74 deficient mice from DSS-induced body weight loss, colon shortening, and tissue damage measured by the histological score and FITC-dextran analysis compared to normal wild-type mice. We further assessed epithelial layer integrity by immunofluorescence staining for the Claudin-3 tight junction marker. In keeping with the severe intestinal damage observed, extensive loss of Claudin-3 was found in CD74 deficient mice after treatment with DSS. Also, myeloperoxidase (MPO) levels, a widely used marker of intestinal inflammation, was significantly higher in the colonic tissue of CD74 deficient mice.

CONCLUSION:

Thus, our findings support the hypothesis that an inferior response to anti-TNF drugs occurs with defective CD74 signaling, and provides a novel insight into the mechanism of treatment failure. Whether CD74 gene variants can be used to predict success in a personalized medicine approach to the management of IBD should be a focus of future research.
832 Pharmacokinetics and Exposure-Response Relationships of Ustekinumab in Patients With Ulcerative Colitis: Results From the UNIFI Induction and Maintenance Studies
Authors: Adedokun Omoniyi J. , Xu Zhenhua , Marano Colleen , O’Brien Christopher , Szapary Philippe , Zhang Hongyan , Johanns Jewel , Leong Rupert W L , Hisamatsu Tadakazu , Van Assche Gert , Danese Silvio , Abreu Maria T. , Sands Bruce E. , Sandborn William J.
Published: October 2019

INTRODUCTION:

Serum concentrations of monoclonal antibody-based biologics have been shown to correlate with their efficacy. PK, exposure-response (ER), and immunogenicity of ustekinumab (UST) were evaluated in UNIFI induction and maintenance studies in UC. Induction results were presented previously.

METHODS:

PK, immunogenicity, efficacy & safety data were obtained from induction and maintenance Phase 3, double-blind, PBO-controlled trials in adults with moderate-severe UC. Pts (n = 961) in the induction study received a single IV infusion at Wk0 of PBO, UST 130 mg, or UST ∼6 mg/kg UST. Responders to a single IV infusion of UST (n = 523) were randomly assigned to receive SC PBO, UST 90 mg q12w, or UST 90 mg q8w. Blood samples were collected to measure serum UST concentration and antibodies to ustekinumab. Relationships between serum UST concentrations & efficacy measures, and safety outcomes were evaluated.

RESULTS:

Serum UST concentrations over time were dose proportional, unaffected by concomitant immunosuppressants, & similar between pts who were biologic failures & non-failures. Median peak serum UST concentrations in the induction study were 43.2 μg/mL & 127.0 μg/mL for the 130 mg & ∼6 mg/kg dose groups, respectively. At induction Wk8, median UST concentrations were 2.51 μg/mL & 8.59 μg/mL, respectively. Steady-state was reached by the start of the second SC maintenance dose. Median steady-state trough serum UST concentrations over time in the UST q8w group (2.69 to 3.09 μg/mL) were 3-fold higher than in the q12w group (0.92 to 1.19 μg/mL). Serum UST concentrations were positively associated with response & remission rates (Table 1), and there was an inverse association between serum UST concentrations and CRP and fecal calprotectin levels. No relationship was observed between serum UST concentrations & the incidence of infections, serious infections or SAEs during induction or maintenance. 3.4% of pts receiving UST maintenance had antibodies to UST through 1 year using a drug-tolerant assay vs. 9.1% with PBO; no impact of antibodies on efficacy was observed.

CONCLUSION:

Serum UST concentrations were approx. dose-proportional. A positive ER of serum UST with clinical efficacy measures and an inverse relationship with inflammatory markers was observed during UST IV induction & SC maintenance. Adverse events including infections did not increase with increased serum UST concentrations. These findings are consistent with those in UST for Crohn’s disease.
837 Short Chain Fatty Acid Profiles Are Altered by Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease and Recurrent Clostridioides difficile Infection
Authors: Allegretti Jessica R. , Mullish Benjamin , Hurtado Jonathan , Carrellas Madeline , Marcus Jenna , Phelps Emmalee , Pettee William , Marchesi Julian , McDonald Julie A.K. , Barker Grace , Blanco Jesus Miguens , Garcia Perez Isabel , Kelly Colleen R. , Grinspan Ari , Fischer Monika
Published: October 2019

INTRODUCTION:

Recurrent C. difficile infection (rCDI) is a major challenge among patients with inflammatory bowel disease (IBD). Perturbation of microbiota-mediated metabolism of short chain fatty acids (SCFA) has been reported in IBD patients. Fecal microbiota transplantation (FMT), an established therapy for rCDI, alters gut microbiota composition, but effects on SCFA are unclear. Accordingly, this study assessed SCFA profiles in IBD patients with rCDI pre- and post-FMT.

METHODS:

This open-label, prospective, single-arm multi-center cohort study enrolled patients from 4 tertiary care centers. Patients with IBD and ≥2 episodes of CDI received a single colonoscopic FMT from a universal stool bank. The primary outcome was CDI recurrence up to week 8 defined as diarrhea and EIA-positive toxin testing for C. difficile. Stool for metabolomic profiling was collected pre-FMT and week 1, 8 and 12 weeks post-FMT. A targeted gas chromatography-mass spectrometry protocol was used for the identification and quantification of SCFA. SCFA concentrations were analyzed via univariate analysis, comparing groups (e.g. pre- vs post-FMT).

RESULTS:

37 participants were enrolled, with mean age of 37.6 years (range 20-76) and primarily female (n = 21, 57%). 14 had Crohn’s disease (CD) (mean HBI = 6.4) and 23 had ulcerative colitis (UC) (mean Partial Mayo Score = 4.5). Mean baseline fecal calprotectin was 1804.8 +/- 2307.7 Overall, 3 participants (8%) experienced FMT failure with confirmed EIA-positive stool, and the there were no related serious adverse events. Among the nine SCFAs assessed, including two branched chain fatty acids (isovalerate and isobutyrate) most were significant altered by FMT, with rapid and sustained changes (with the exception of acetate, in which no change was appreciated) (Figure 1). Additionally, 2-hydroxybutyrate and lactate, two markers of metabolic stress, were significantly reduced after FMT. Furthermore, the baseline stool samples of those who went on to recur were compared to those who did not (Figure 2); though not significant, there was a trend towards reduced baseline levels for butyrate, propionate and caproate among those who recurred.

CONCLUSION:

To our knowledge, this is the largest prospective trial to assess the effect of FMT in patients with IBD-CDI. The data suggests the efficacy and safety profile is better than previous reports. SCFAs were increased significantly post-FMT, and may offer insight into mechanism of clinically efficacy seen in this study.
840 Patient Characteristics and Outcomes Associated With Cannabis Abuse or Dependence Among Hospitalized Patients With IBD: A U.S. Time-Trend Analysis and Population-Based Cohort Study
Authors: Dalal Rahul S. , Lichtenstein Gary R.
Published: October 2019

INTRODUCTION:

Cannabis is a commonly used yet restricted substance with potential anti-inflammatory and analgesic properties. Patients with inflammatory bowel disease (IBD) use cannabis specifically for symptom relief, however its safety and efficacy in ulcerative colitis (UC) and Crohn’s disease (CD) are poorly characterized. Among hospitalized patients with IBD, temporal trends of heavy cannabis use and its effects on hospitalization outcomes are unclear. We therefore attempted to assess yearly trends in cannabis abuse or dependence (CAoD) and associated hospitalization outcomes among hospitalized patients with IBD.

METHODS:

This was a retrospective population-based cohort study utilizing the Healthcare Utilization Project (HCUP) National Inpatient Sample (NIS) database from 2005 to 2014. We performed a time-trend analysis of CAoD among IBD patients using International Classification of Disease, ninth revision clinical modification (ICD-9-CM) diagnosis codes for cannabis dependence, non-dependent cannabis abuse, CD, and UC, in any diagnosis position. For a multivariable analysis of the effect of CAoD on hospitalization outcomes, IBD-specific hospitalizations were identified by a primary diagnosis of IBD or a secondary diagnosis of IBD with a primary diagnosis of an IBD-related complication. Multivariable linear or logistic regression was used to assess the association of CAoD on hospital length of stay (LOS), total charges, in-hospital mortality, and IBD surgery. The weighted NIS sample was used for all analyses.

RESULTS:

Between 2005 and 2014, we identified 2,788,246 discharges with a diagnosis of IBD and 1,049,837 discharges for IBD-specific hospitalizations, among which 10,293 (1.0%) were associated with CAoD. Among those with CAoD, 74.9% had CD (vs. 25.1% UC, P < 0.01), 64.9% were male, 56.9% were cigarette smokers, and 38.6% were in the 21-30 y age group (Table 1). There was an average annual increase of 9.1% (P < 0.01) for CAoD among hospitalized IBD patients from 2005 to 2014 (Figure 1). After multivariable regression, CAoD was independently associated with decreased LOS (-0.4 d; 95% CI -0.6–-0.2 d) and odds of IBD surgery (OR 0.8, 95% CI 0.7–0.9) (Table 2). There was no association with total charges and no IBD patients with CAoD died during their hospitalization.

CONCLUSION:

CAoD may be associated with decreased LOS and odds of IBD-related surgery among hospitalized IBD patients. Further research is needed to assess the impact of heavy cannabis use on long-term outcomes in patients with IBD.
842 Impact of Response and Inflammatory Burden at Start of Maintenance Therapy on Clinical Efficacy of Ustekinumab Dosing Regimen in UC: Week 44 Results From UNIFI
Authors: Panaccione Remo , Peyrin-Biroulet Laurent , Danese Silvio , Marano Colleen , O’Brien Christopher D. , Szapary Philippe , Zhang Hongyan , Johanns Jewel , Leong Rupert W L , Arasaradnam Ramesh P. , Rowbotham David , Abreu Maria T. , Sands Bruce E.
Published: October 2019

INTRODUCTION:

The UNIFI maintenance study was a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study in pts with moderate to severely active ulcerative colitis (UC) who failed conventional or biologic therapy and were in clinical response 8 wks after receiving a single ustekinumab (UST) IV induction dose. In this study, pts were randomized to placebo, UST 90 mg SC q8w or q12w.

METHODS:

To examine the relative efficacy of the UST 90 mg SC q8w or q12w maintenance regimens, subgroup analyses were performed for outcomes of clinical remission, symptomatic remission, and endoscopic improvement at Wk44 for pts who did and did not achieve these endpoints at the start of maintenance. Analyses of clinical remission and endoscopic improvement at Wk44 based on pre-specified cut-points of the concentrations of inflammatory biomarkers (CRP [≤3 mg/L, >3 mg/L] and fecal calprotectin [≤250 mg/kg, >250 mg/kg]) at maintenance baseline were also conducted.

RESULTS:

For pts who had achieved clinical remission, symptomatic remission, or endoscopic improvement at maintenance baseline, efficacy of UST q8w and q12w regimens for the respective endpoint at Wk44 was similar (Table 1). By contrast, for pts who did not achieve clinical or symptomatic remission or endoscopic improvement at maintenance baseline, UST q8w demonstrated greater efficacy than UST q12w for that endpoint at Wk44. Pts with low inflammatory burden marked by CRP ≤3 mg/L at maintenance baseline achieved similar efficacy at Week 44 with UST q8w and q12w dosing regimens as measured by clinical remission and endoscopic improvement (Table 1). By contrast, pts with high inflammatory burden, marked by CRP >3 mg/L at maintenance baseline, achieved greater efficacy at Wk44 with UST q8w versus q12w dosing over the endpoints. Generally similar trends were seen in pts with fecal calprotectin measurements for low (≤ 250 mg/kg) and high (>250 mg/kg) inflammatory burden at maintenance baseline.

CONCLUSION:

Among pts with a clinically meaningful response to a single IV induction dose of UST, maintenance treatment with UST q8w or q12w demonstrated similar efficacy at Wk44. By contrast, the efficacy of UST q8w at Week 44 was greater than the q12w regimen for pts with higher inflammatory burden or who did not achieve clinical or symptomatic remission or endoscopic improvement at Wk8. These data suggest that multiple clinical measures can help inform the decision on the most appropriate maintenance dosing regimen for UST in the treatment of pts with UC.
845 Patient and Physician Assessment of Disease Burden in Patients With Early UC: 2-Year Data From ICONIC
Authors: Ghosh Subrata , Sensky Tom , Casellas Francesc , Kligys Kristina , Petersson Joel , Peyrin-Biroulet Laurent
Published: October 2019

INTRODUCTION:

ICONIC is an observational study assessing disease burden in adults with ulcerative colitis (UC) under routine care over 2 years. The final analysis of the study is presented.

METHODS:

Adults with early UC (diagnosed ≤36 months) were enrolled irrespective of disease severity or treatment. The primary objective was to evaluate Pictorial Representation of Illness & Self-Measure (PRISM) as a tool to assess disease associated suffering. Lower PRISM scores represent greater suffering associated with illness. Correlation between pt and physician perception of disease was also assessed. Patient self-assessments included PRISM, Patient Health Questionnaire-9 (PHQ-9), Short IBD Questionnaire (SIBDQ), and patient-modified Simple Clinical Colitis Activity Index (P-SCCAI). Physician assessments included clinical parameters, PRISM, and SCCAI. Data are presented as-observed. Mean differences between pt and physician measures, and differences between the 2-year and first visits were calculated using Wilcoxon signed-rank test. Correlation between PRISM and SIBDQ, PHQ-9, and SCCAI were performed using Spearman correlation.

RESULTS:

A total of 1806 patients were enrolled; 336 (18.6%) discontinued the study. 2-year data were available for 1265 pts. Mean ± SD patient-reported PRISM score and P-SCCAI were significantly different than the physician measures, with pts reporting higher disease burden than that perceived by the physician (pt PRISM: 5.1 ± 2.5 and physician PRISM: 5.6 ± 2.4; P < 0.0001; P-SCCAI: 2.5 ± 2.8 and SCCAI: 1.3 ± 2.1; P < 0.0001; Table 1). A high correlation was observed between pt and physician PRISM scores and between P-SCCAI and SCCAI. Mean ± SD scores for PHQ-9 and SIBDQ were 4.2 ± 4.6 and 55.7 ± 11.6, respectively. Significant differences in mean ± SD scores between the 2-year visit and the first visit were observed for all measures (PHQ-9: -1.8 ± 5.5; P-SCCAI: -1.6 ± 4.0; SCCAI: -1.5 ± 3.2, SIBDQ: 6.8 ± 13.9; patient pt PRISM: 1.2 ± 3.0; physician PRISM: 1.3 ± 2.9; P < 0.0001 for all measures).

CONCLUSION:

PRISM may be a valuable tool to assess disease burden in pts recently diagnosed with UC. Although pt and physician measures of disease related suffering and disease severity were strongly correlated, the perception of UC-related burden significantly differed between physician- and pt- assessments. These discrepancies between pt and physician ratings warrant further investigation.