bluuebunny/crossref_metadata_2025 huggingface dataset:
684 Crohn's Disease and Risk of Surgery Based on Disease Location and Phenotype
Authors: Young Chase K. , Jahandar Donya R. , Hamdeh Shadi , Kalot Mohamad , Makki Maha , Olyaee Mojtaba
Published: October 2019

INTRODUCTION:

Crohn's disease (CD) is a chronic inflammatory disease that can affect any segment of gastrointestinal tract. Over 50% of patients develop complications like strictures or fistula formation and past studies report 50% of Crohn's disease patients require surgery within ten years from disease diagnosis. We aim in this study to determine the risk of surgery in Crohn's disease based on disease location and phenotype.

METHODS:

A retrospective study was conducted evaluating CD patients on anti TNF agents seen at the University of Kansas Medical Center from data inceptions until May, 2018. Patients were stratified by disease location (ileum, colon, ileocolon, or upper GI tract) as well as phenotype (stricturing, fistulizing, luminal or mixed patterns). The primary outcome was the need of surgery based on phenotype and disease location. The secondary outcome was the time to start anti TNF therapy in each category based on disease location and phenotype.

RESULTS:

Data from 229 patients with CD was analyzed. From which, 128 underwent surgery. Our analysis showed that Patients with the fistulizing type had the highest rate of surgery with 51/62 patients (82% P < 0.0001) with (mean = 5.69 ± 9.3 years to start anti TNF) and patients with the luminal subtype had the lowest rate of surgery with 26/89 patients (29%, P < 0.0001) with (mean = 3.77 ± 8.88 years to start anti TNF) in comparison to patients with other subtypes stricturing, stricturing + fistulizing, stricturing + luminal, fistulizing + luminal or Stricturing + fistulizing + luminal who had 31/50 (62%, P = 0.33, mean = 7.02 ± 8.89 years), 11/15 (73%, P = 0.16 mean = 10.9 ± 13.2), 2/3 (66% P = 1, mean = 0.33 ± 0.58), 6/9 (66%, P = 0.74 mean = 4.89 ± 6.), and 1/1 (100% P = 1, mean = 2) respectively. Regarding the location of Crohn's disease, patients with ileocolonic involvement had the highest rate of surgery with 64.2% and with a mean of 6.15 ± 9.95 years to start anti TNF, Whereas patients with only colonic involvement have the lowest rate of surgery of 37.5% with a mean of 4.33 ± 8.41 years to start anti TNF. Patients with the disease in other locations; ileal and upper GI had 39% rate of surgery (with a mean of 2.64 ± 4.25 years to start anti TNF) and 61.9% % rate of surgery (with a mean of 8.43 ± 11.74 years to start anti TNF) respectively.

CONCLUSION:

Patients with CD with fistulizing phenotype and ileocolonic location are at the highest risk for surgery, whereas patients with luminal phenotype and colonic location are at the lowest risk for surgery.
687 Epidemiology of Older-Onset Inflammatory Bowel Disease in the United States Between 2014 and 2019: A Population-Based National Study
Authors: Mansoor Emad , Saleh Mohannad Abou , Sarmini Muhammad Talal , Chouhan Vijit , Regueiro Miguel , Katz Jeffry , Cooper Gregory S.
Published: October 2019

INTRODUCTION:

Recent studies have described the rising incidence of older-onset IBD (>60 yo) in the Western world. However, the epidemiology of older-onset IBD in the United States (US) has not been studied extensively and is subject to debate. We sought to describe the prevalence and incidence of older-onset IBD in the US between 2014 and 2019 utilizing a large population based database.

METHODS:

We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated healthcare systems in the US from 1999 to 2019. We identified an aggregated patient cohort of eligible patients with a "first-ever" diagnosis of “Crohn's disease” or “Ulcerative Colitis” at age >60 years between June 2014 and 2019, based on Systemized Nomenclature of Medicine – Clinical Terms. We calculated the 5-year prevalence older-onset IBD overall, among different patient groups and stratified by decades. Furthermore we also calculated the incidence of older onset IBD over last 1 year between 2018 and 2019.

RESULTS:

Of the 10,726,480 individuals aged >60 yo active in the database from June 2014-2019, we identified 38,730 and 40,230 individuals with a diagnosis of CD and UC with an overall prevalence rate of 0.36% and 0.38% respectively. The prevalence of older-onset CD was increased in females at 0.38% [OR: 1.13, 95% CI: 1.11-1.16, P < 0.0001] compared to males at 0.34%, and Caucasians at 0.45% [OR: 1.65, 95% CI: 1.59-1.72, P < 0.0001] compared to African-Americans at 0.27%. The prevalence of older-onset UC was increased in females at 0.39% [OR: 1.07, 95% CI: 1.04-1.09, P < 0.0001] compared to males at 0.36%, and Caucasians at 0.47% [OR: 1.67, 95% CI: 1.60-1.74, P < 0.0001] compared to African-Americans at 0.28% (Figure 1). Among age-stratified analyses, as expected, the prevalence of both CD and UC was lowest in the 60-69 yo decade, increased with subsequent decades and downtrended in the 90+ age group (Figure 2). The incidence of older onset CD and UC over last 1 year between 2018 and 2019 was 0.21% and 0.20% respectively.

CONCLUSION:

This is one of the first large studies to date that has described the prevalence and incidence of older-onset IBD in the US. We found that the prevalence of older-onset CD and UC is higher in females and Caucasians. We further identified that older-onset CD and UC is most prevalent in the 80-89 yo decade of life and decreases thereafter.
691 Risk Factors for and Frequency of CT Scans in Inflammatory Bowel Disease Patients Seen in the Emergency Department
Authors: Glassner Kerri , Euers Lindsay , Gajula Prianka , Jones-Pauley Michelle , Ezeana Chika F. , Puppala Mamta , Wang Lin , Wong Stephen T. , Oglat Ayah , Nickerson Stephanie , Abraham Bincy
Published: October 2019

INTRODUCTION:

Patients with inflammatory bowel disease (IBD) frequently have CT scans performed during emergency department (ER) visits and hospitalizations. Previous studies found that the younger a patient is when a CT scan is performed, the higher the risk of malignancy over a lifetime. Younger IBD patients have also been shown to have an increased frequency of ER visits, thus placing them at risk for repeat CT scans. Our aim was to determine the risk factors for and frequency of CT scans performed in all 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 (CD), ulcerative colitis (UC) or indeterminate colitis from the EMR. There were 559 unique patients with 1489 unique visits confirmed after individual chart review. Data was collected on demographics including age, sex, and ethnicity; medications; and imaging (CT of the abdomen/pelvis).

RESULTS:

Of the 559 patients with ER visits, 61% were female with an average age of 50 (range 18-95). There were 65% with CD, 34% with UC, and less than 1% had indeterminate IBD. Of these, 23% were on a biologic, 15% on an immunomodulator, and 27% were treated with steroids for IBD. There were 325 patients (58%) with 599 visits during which a CT scan was performed, and of these 88% were ordered in the ER. The average age was 46, and 60% were female. IBD was the primary reason for the visit in 66%. There were 68% with CD, 31% with UC, 24% on a biologic medication, 17% immune modulator, and 35% received steroids. Older age was associated with a decreased risk of CT scan P = <2.2 × 10-16, R -0.002, as well as UC compared to CD, P = 0.009, R -0.06. There was an increased risk of CT scan in patients on a biologic, P = 0.038, R 0.04, immunomodulator, P = 0.039, R 0.029, or when steroids were given for IBD, P = 1.44 × 10-13, R 0.102. There was an increased risk of undergoing a CT scan when the primary reason for the visit was for IBD, P = <2.2 × 10-16, R 0.372.

CONCLUSION:

Over half of the IBD patients in our study population had CT scans performed, which almost always occurred in the ER. There was an increased risk of a CT in those on a biologic, immunomodulator, or steroids for IBD, suggesting that more severe disease may contribute. Younger patients and those with CD also had an increased risk. Guidelines are needed to limit repeat CT scans in young IBD patients to reduce the risk of increased malignancy over their lifetime.
692 Low Levels of Ustekinumab Despite Dose Escalation Is a Risk Factor for Surgery
Authors: Glassner Kerri , Perry Caroline , Wilhite Amanda , Abraham Bincy
Published: October 2019

INTRODUCTION:

Ustekinumab is an IL-12/23 inhibitor used for the treatment of Crohn's disease (CD). Previous studies have suggested that dose escalation to every 4-week intervals can be beneficial in patients who do not achieve a clinical response on every 8-week maintenance dosing. However, safety and efficacy is unknown in CD patients escalated to more frequently than every 4-week intervals in patients who continue to have low trough drug levels.

METHODS:

We performed a retrospective chart review of patients on ustekinumab for CD who had dosing escalation to every two weeks (Q2) due to persistent low drug levels (<5 µg/mL) despite being on q4 weeks (Q4) maintenance dosing and clinically losing response.

RESULTS:

Out of 200 CD patients on ustekinumab 90 mg subcutaneous (SQ) maintenance in our IBD program, 112 underwent reactive therapeutic drug monitoring for loss of response or incomplete response to therapy. Of the 112 with drug levels, none had anti-drug antibodies, but 80 patients had levels <5 mcg/mL. All 80 patients were frequency escalated to q4 week dosing. Of these, 12 patients continued to have low ustekinumab trough levels at week 4 (<5 mcg/mL) and thus were escalated to Q2 week dosing. Eight of the 12 patients had IV reinduction dosing prior to dose escalation to Q2 frequency. Of the 12 patients, 6 (50%) required surgery for their active Crohn's disease. These patients were on Q2 week dosing for median of 16 weeks (range 1-68) prior to surgery. All 6 (100%) were able to be de-escalate to less frequent dosing after surgery. Two patients that were unable to de-escalate their dosing frequency are planning for surgery in the near future. The remaining four patients were able to de-escalate to Q4 dosing after clinical response. See full details in Table 1. No adverse events unrelated to their Crohn's disease, including infections or other safety markers were noted.

CONCLUSION:

Low levels of ustekinumab despite escalation of dosing to every 2 weeks may suggest a need for Crohn's disease related surgery. In our study, all patients who underwent surgery were able to de-escalate to lower dosing frequency suggesting that high inflammatory disease burden contributed to the low levels of ustekinumab. Further studies are needed to assess the safety and efficacy of high frequency dosing of ustekinumab.
697 Safety of Ustekinumab in Inflammatory Bowel Diseases: Integrated Safety Analysis of Results From Phase 2 and 3 Studies in Crohn's Disease and Ulcerative Colitis
Authors: Sandborn William J. , Ghosh Subrata , O'Brien Christopher D. , Ott Elyssa , Marano Colleen , Zhou Yiying , Volger Sheri , Tikhonov Ilia , Gasink Christopher , Danese Silvio , Sands Bruce E.
Published: October 2019

INTRODUCTION:

Ustekinumab (UST) is a well-established therapy in Crohn's disease (CD) and psoriatic diseases. UST was safe and effective in phase 3 ulcerative colitis (UC) studies. Pivotal studies of UST in CD (UNITI, IMUNITI) and UC (UNIFI) had similar designs, which allows for integrated analysis across both indications. We present an integrated safety analysis of UST in inflammatory bowel disease (IBD).

METHODS:

Data from 6 phase 2/3 studies were pooled, and safety was evaluated through 1 year of follow-up. In phase 3, pts received a single IV placebo (PBO) or UST (130 mg or ∼6 mg/kg) induction dose followed by SC maintenance doses of PBO or UST (90 mg q8w or q12w). Concomitant immunomodulators (IMM) and corticosteroids were permitted. All pts who received ≥1 dose of UST were included. Safety outcomes through 1 year are presented as the number of pts with events per 100 patient-years (PY) of follow-up.

RESULTS:

At induction baseline (2370 pts in pooled phase 3 IBD studies), median age was 38.0 years, 46.9% were receiving corticosteroids, 30.8% were receiving IMM, 53.0% had failed biologics, and 37.1% were naïve to biologics. In phase 3 IBD studies, through Wk8 of PBO-controlled induction, the frequency of key safety events was similar between UST and PBO (Table 1). In addition, through 1 year across phase 2/3 IBD studies (Table 2), numbers of pts per 100 PY with key safety events were similar between treatment groups. The most frequently occurring AEs (excluding diseases under study) were arthralgia (PBO 16.93 vs UST 16.56), headache (16.43 vs 16.50), nausea (13.25 vs 11.94), and abdominal pain (14.59 vs 11.54); infections were nasopharyngitis (16.26 vs 18.11) and upper respiratory tract infection (11.40 vs 11.36). For serious infections, the CD-specific event of anal abscess occurred in PBO 2.02 and UST 0.90 pts per 100 PY. When CD-specific events were excluded, overall rates of serious infections were similar between UC and CD. The only malignancy (excluding NMSC) reported in >1 UST-treated patient was prostate cancer; no lymphomas were reported through 1 year. Two pts receiving UST (0.12 per 100 PY; both had UC) died from events that investigators considered to be unrelated to study agent (esophageal varices hemorrhage and acute respiratory failure during thyroid surgery).

CONCLUSION:

The safety profile of UST in pts with UC and across integrated IBD indications through 1 year was favorable and consistent with the established safety profile in pts with CD and psoriatic disease.
699 Role of C-Reactive Protein as a Marker for Disease Course in Obese Patients With Inflammatory Bowel Disease
Authors: Ye Chengcheng , Higgins Ixavier , Iskandar Heba
Published: October 2019

INTRODUCTION:

Currently, the disease course and clinical outcomes of obese patients with inflammatory bowel disease (IBD) have been mixed. This study aims to compare biomarkers of inflammation such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in both obese and non-obese African American (AA) and Caucasian populations.

METHODS:

We conducted a prospective observational study of consecutive Crohn's disease (CD) and ulcerative colitis (UC) patients in the outpatient setting at a tertiary referral center between 2014-2017. Body mass index (BMI), ESR, CRP, hemoglobin (Hgb) were measured at 2 consecutive visits. Obesity was defined as a BMI ≥30. The Wilcox signed rank test was used to compare continuous variables, and the Chi square test for categorical variables. A multivariate logistic regression model was created to look at change in CRP (no change, increase by half, decrease by half) from initial to follow-up visit. The regression model analysis included ethnicity, gender, BMI, type of IBD (CD versus UC), age, alcohol use, tobacco use, hypertension, kidney disease, heart disease, and treatment as covariates.

RESULTS:

The study included 92 subjects, 65% had CD and 30% were AA (Table 1). The average time between visits was 136 days. In the obese group, 33% were AA and 70% were female. Also, a larger portion of CD patients were obese compared to UC patients (37% and 11% respectively with P = 0.03). There was a significant decrease in the CRP in the obese group (P = 0.029) whereas non-obese individuals had an increase in CRP (Table 2). There was no significant difference in ESR and hemoglobin (Hgb) between obese and non-obese individuals. 63 patients where included in the regression model, which showed that a decrease in CRP was significantly associated with obesity (P = 0.0081) when adjusted for the above covariates. Overall, obese individuals were more likely to experience no change in CRP or a decrease in CRP while non-obese individuals were more likely to have a rise in CRP. There was no difference in clinical disease activity indices (HBI/SCCAI) between obese and non-obese patients.

CONCLUSION:

In our study, the obese patients were more likely to be female, have CD, and be Caucasian. While there was no difference in Hgb or ESR in obese versus non-obese, there is a difference in CRP. CRP could have importance as a sensitive marker for disease course in patients whose BMI ≥30. A larger cohort may provide further insight into this observation.
700 Mild Endoscopic Activity Is Associated With an Increased Risk of Relapse in Patients With Ulcerative Colitis
Authors: Feldman Harris , George Lauren A. , Abutaleb Ameer , Hine Ashley M. , Zullow Samantha , Axelrad Jordan E. , Hudesman David P. , Cross Raymond K.
Published: October 2019

INTRODUCTION:

Currently, endoscopic remission in ulcerative colitis (UC) is defined using the Mayo Endoscopic subscore (MES), with a score of 0 (normal mucosa) or 1 (erythema, decreased vascular pattern, mild friability) representing mucosal healing. However, it is not clear if clinical outcomes differ between patients with a MES of 0 and 1. The aim of our study was to evaluate differences in relapse rates between patients with MES of 0 and 1.

METHODS:

UC patients who underwent colonoscopy at 2 IBD referral centers from 2012 to 2017 were identified. Inclusion criteria consisted of patients with a MES score of 0 or 1, no prior colectomy, and outpatient follow up for a minimum of 1 year after colonoscopy. Data was collected for demographics, disease characteristics, medications, time from last disease flare and inflammatory biomarkers. The primary outcome was defined as a composite of relapse requiring change in medical therapy, new steroid use, UC-related hospitalization, and colectomy. Chi Square, Fisher's exact and logistic regression modeling were used in statistical calculations.

RESULTS:

446 UC patients were identified, with 228 (51%) and 218 (49%) having a MES of 0 and 1 respectively. 78% were Caucasian, 52% were female and mean age was 40 ± 15 years. 20, 34, and 46% had proctitis, left sided colitis and extensive or pancolitis, respectively. 46% of patients were on either a 5-ASA alone or no medical therapy, while 46% were on biologics and 27% were on biologic therapy with an immune suppressant. Within 1 year from colonoscopy, 97 (22%) had a change in medical therapy and 66 (15%) were prescribed steroids. Only 8 and 4 patients were hospitalized for UC or underwent colectomy, respectively. UC patients with a MES of 1 were more likely to experience a relapse (P < 0.01) (Table 1). After adjusting for race, disease extent, and medication use, a MES of 1 was the only factor associated with an increased the risk of relapse (aOR 2.54, 1.61-4.01) (Table 2).

CONCLUSION:

Patients with mild endoscopic activity by MES were at increased risk for relapse compared to patients with no endoscopic activity. In this population of UC patients, MES score was the only variable that predicted future relapse. Future studies are needed to classify low and high risk patients with mild endoscopic activity through evaluation of novel biomarkers and histology. Gastroenterologists should consider enhanced monitoring and/or changes in medical therapy based on the presence of even mild inflammation.
702 Knowledge, Perception, and Use of Cannabis Therapy in Patients With Inflammatory Bowel Disease
Authors: Cruz-Cruz Jorge , Muñiz Luis , Negron Frances , Ramos Luis , Oquendo Kimberly Hernández , Emanuelli Natalie I. , Garau Fabiola , Torres Esther
Published: October 2019

INTRODUCTION:

Cannabis has been proposed as a therapeutic option for Inflammatory Bowel Disease (IBD), but its benefit is controversial. Because of the chronic nature of IBD and lack of a cure, patients are turning to complementary and alternative medicine, including cannabis, to achieve symptom control. In 2017, the government of Puerto Rico legalized medical cannabis for several indications including IBD. Prevalence of cannabis use in our patients with IBD is unknown. The aims of this study were to estimate the prevalence of cannabis use in patients with IBD, and evaluate patient knowledge and perception regarding cannabis use and effects.

METHODS:

A cross-sectional study was performed in a sample of 100 individuals with IBD from the clinics at the UPR Center for IBD. A voluntary anonymous questionnaire survey was provided. It consisted of 19 questions including demographics, diagnosis and cannabis use. For patients who reported cannabis use, specific questions regarding mode, frequency, purpose, source, and cost of cannabis were assessed. The study was approved by the MSC IRB.

RESULTS:

Most subjects were young patients between 21-30 years old (39%) with Crohn's Disease (78%). Male to female ratio was 1:1. Although the largest group (39%) reported moderate knowledge about medical cannabis, 37% reported lack of knowledge about possible therapeutic properties in IBD. Of the 63% that had considered cannabis use, only 21% had consulted with their physician and 27% reported use of cannabis. Of these, only 37% are licensed for medical cannabis use. Among users, 56% reported that the purpose was to relieve IBD related symptoms. The most frequent formulations used were vaporized and smoked. Among cannabis users, 30% reported daily use. Most patients (30%) spend between $51-100 monthly. Only 15% reported severe IBD. The majority (63%) reported an improvement of symptoms and 67% an improvement in quality of life; 81% of users would recommend cannabis use for IBD. The probability of wanting physician approval of medical cannabis for IBD was related with its use (P = 0.03) but not related to perceived knowledge (P = 0.36).

CONCLUSION:

This study provides insight about estimated prevalence, knowledge, purpose, pattern of use, costs and perception about cannabis use in patients with IBD. Physician awareness and strategies to address the issue with patients are needed.
703 Fatigue Is Inversely Associated With Endoscopic but Not Histologic Remission in IBD Patients
Authors: Lakhani Komal , Durbin Laura , Agrawal Manasi , Bhardwaj Richa , Swaminath Arun
Published: October 2019

INTRODUCTION:

Fatigue is a subjective and underdiagnosed symptom prevalent in nearly half of all inflammatory bowel diseases (IBD) patients and can be highly debilitating. It is more common in Crohn's disease (CD) than in ulcerative colitis (UC) and is associated with disease activity. The purpose of our study was to determine patient and disease variables associated with fatigue in a tertiary referral center in New York City.

METHODS:

IBD patients were asked to complete the validated 8-item PROMIS Fatigue Short Form 8a, with a T-score of ≥50 and <50 indicating high and low levels of fatigue over the previous 7 days. Variables such as age, sex, IBD type, body mass index (BMI), and disease remission status (clinical, endoscopic, and histologic) were determined on chart review at the same time.

RESULTS:

Of 187 IBD patients included in the study, 113 had CD (Table 1). In our sample, 48.7% of all IBD patients reported high fatigue. Fatigue was not associated with age, sex, BMI, or IBD type (Table 2). In multivariable models, adjusted for age and sex, clinical remission (OR 0.42, 95% CI 0.23-0.76) and endoscopic remission (OR 0.44, 95% CI 0.22-0.88), but not histologic remission (OR 0.43, 95% CI 0.18-1.01), were inversely associated with fatigue.

CONCLUSION:

Fatigue is a common symptom in IBD patients and is inversely associated with clinical and endoscopic, but not histologic, remission in this single-center cross-sectional study. These findings corroborate the role of disease activity in fatigue in IBD and emphasize the impact of achieving clinical and endoscopic remission.
705 Tofacitinib for the Treatment of Ulcerative Colitis: An Update on the Analysis of Malignancy Rates From the UC Clinical Program
Authors: Lichtenstein Gary R. , Ciorba Matthew A. , Rogler Gerhard , Quirk Daniel , Thorpe Andrew J. , Pedersen Ronald D. , Lawendy Nervin , Chan Gary , Panés Julian
Published: October 2019

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). We present an updated analysis of adjudicated malignancies in the UC clinical development program as of Sep 2018.

METHODS:

Malignancies were evaluated from 4 randomized placebo (PBO)-controlled studies (Phase [P] 2 and P3 induction studies [NCT00787202; NCT01465763; NCT01458951], 1 maintenance P3 study [NCT01458574]), and an ongoing, open-label, long-term extension (OLE) study (NCT01470612).
1–3
Three cohorts were analyzed: Induction (P2/P3 induction studies), Maintenance (P3 maintenance study), and Overall (patients [pts] receiving tofacitinib 5 or 10 mg twice daily [BID] in P2, P3, or OLE studies). Proportions and incidence rates (IRs; unique pts with events per 100 pt-years [PY] of exposure) were evaluated for malignancies (excl. non-melanoma skin cancer [NMSC]) and NMSC. For Overall Cohort analysis, pts were categorized based on the average daily tofacitinib dose: predominant dose (PD) 5 or 10 mg BID. For P3 studies, an independent adjudication committee reviewed all potential malignancies.

RESULTS:

1157 pts were evaluated for malignancies (2404 PY of tofacitinib exposure; up to 6.1 years of treatment). Malignancies (excl. NMSC) occurred in 0 Induction Cohort pts, 1 PBO-treated Maintenance Cohort pt, and 17 Overall Cohort pts (IR 0.69; 3 received a PD of tofacitinib 5 mg BID [IR 0.49] and 14 a PD of 10 mg BID [IR 0.75]; Table 1). NMSC occurred in 2 tofacitinib-treated Induction Cohort pts, 4 Maintenance Cohort pts (3 with 10 mg BID-treated pts, IR 1.91; and 1 PBO-treated pt, IR 0.97), and 19 Overall Cohort pts (IR 0.78; 4 had received a PD of 5 mg BID and 15 a PD of 10 mg BID).

CONCLUSION:

Malignancies (incl. NMSC) were observed with tofacitinib in UC. There was no malignancy type clustering (excl. NMSC). The IR of malignancies (excl. NMSC) reported here is similar to those previously reported for UC [4] – suggesting no treatment duration impact on the IR – and for tofacitinib in pts with rheumatoid arthritis and in pts with UC treated with biologics.
5–7
710 Relationship Between Partial Mayo Score and Patient-Reported Outcomes for Ulcerative Colitis Patients in the United States
Authors: Ding Zhijie , Obando Camilo , Izanec James , Sikirica Mirko , Lucas James , Kemp Jessalyn , Muser Erik
Published: October 2019

INTRODUCTION:

Measuring Patient-Reported Outcomes (PROs) is important in understanding how ulcerative colitis (UC) patients perceive their own health status and emotional well-being. This study aims to establish the association between PROs and disease severity measured by partial Mayo score (PMS) using real-world data.

METHODS:

Data were drawn from the Adelphi Disease Specific Programme (a real-world survey of gastroenterologist-completed retrospective chart review and patient self-completion questionnaires) conducted in the US in 2015 and 2017. UC patients (pts) with current or history of moderate-to-severe (mod/sev) disease and/or those having ever been treated with steroids, an advanced therapy (immunomodulator or biologic therapy) or ever had a Mayo score >4 were included in the analysis. Pts self-completed a form containing the EQ-5D and the SIBDQ. Comparisons between pts with a PMS of 0-1 (remission), 2-4 (mild) and 5-9 (mod/sev) at the time of the survey were made using Kruskal-Wallis and Chi-squared tests for continuous and categorical variables, respectively.

RESULTS:

Of the 1389 UC pts included, 410 were classified as being in remission, 646 mild and 333 mod/sev based on PMS at the time of completing the survey. Remission patients had a mean age of 44.8 years, mild 42.6 and mod/sev 39.4 (P < 0.001), with 48.8%, 52.2% and 45.9% female (P = 0.166) and 7.0, 4.5 and 3.0 mean years since diagnosis (P < 0.001), respectively. 7.4% of remission pts, 16.8% mild and 66.8% of mod/sev were currently experiencing a flare or flare-like symptom (P < 0.001). Remission pts had a higher mean overall SIBDQ score compared with mild and mod/sev (Table 1), and higher systemic, social, bowel and emotional subdomain scores (Table 1). Remission pts had a higher EQ-5D score and EQ-5D VAS compared with mild and mod/sev pts. Compared with those of remission patients, subdomains of usual activities, pain/discomfort and anxiety/depression for mod/sev patients were significantly impacted, whilst mobility and social care subdomains showed no significant differences across severity groups.

CONCLUSION:

UC pts with more severe disease according to the PMS self-reported lower quality of life in terms of overall SIBDQ score and worse individual subdomain scores compared to mild patients and patients in remission. They were also more likely to report lower EQ-5D score, likely driven by a significant impact on usual activities, pain/discomfort, and anxiety/depression subdomains.
712 Predictors of Ectopic Pregnancy Among Women With Inflammatory Bowel Disease: A Population-Based Cohort Analysis
Authors: Berera Shivali , Saxena Akriti P. , Dalal Rahul S. , Lichtenstein Gary R.
Published: October 2019

INTRODUCTION:

We have previously demonstrated that there is a higher odds of ectopic pregnancy among women with Crohn's disease (CD) but not ulcerative colitis (UC) compared to those without inflammatory bowel disease (IBD) (Gastroenterol 2019 Abstract 1861). We aimed to further characterize underlying predictors and the incidence rates of ectopic pregnancies over time in this cohort.

METHODS:

A population-based retrospective cohort study using the Healthcare Cost and Utilization Project's (HCUP) Nationwide Inpatient Sample (NIS) was performed from 2005 to 2014. The NIS is the largest all-payer inpatient health care database in the United States. Unique pregnancies were identified using ICD-9-CM diagnosis and procedure codes. National estimates of ectopic pregnancy were created using appropriate weights for each NIS admission. Multivariable logistic regression was used to evaluate the association of UC and CD with ectopic pregnancy while adjusting for age, race, income, primary insurance, hospital size, hospital region, Charlson-Deyo comorbidity index, obesity, chronic steroid use, smoking status, and prior cesarean section. The trend in the incidence rate of ectopic pregnancy was plotted and compared in IBD and non-IBD patients within the study period.

RESULTS:

There were significantly higher rates of ectopic pregnancy in patients with CD versus non-IBD patients (1% vs 0.6%, P < 0.001) and patients with UC (0.5%). Observed predictors for ectopic pregnancy included lack of insurance, higher comorbidity index, chronic steroid use, and smoking (Table 1). While the rate of ectopic pregnancy declined in all patients during the time period, the overall incidence rate was highest in patients with IBD (Figure 1). While further exploring this trend, the incidence of ectopic pregnancy in IBD patients was observed to be higher in age groups 31-40 and 41-50 as compared to younger counterparts (Figure 2a) and patients without IBD (Figure 2b).

CONCLUSION:

Compared to women without IBD, the odds of a pregnancy being ectopic is higher among women with CD but not UC, particularly in patients with lack of insurance, higher comorbidity index, chronic steroid use, and smoking. While the incidence rate of ectopic pregnancy is declining in both patients with and without IBD, older individuals with IBD have an increased risk of ectopic pregnancy compared with younger patients and non-IBD patients. Prospective studies are warranted to further examine this trend and identify mechanisms behind these associations.
714 Increased Risk of Colectomy in Hospitalized Patients With Inflammatory Bowel Disease and Cytomegalovirus Infection
Authors: Castaneda Daniel , Melendez-Rosado Jose , Hasan Badar , Charles Roger
Published: October 2019

INTRODUCTION:

Patients with inflammatory bowel disease (IBD) present flares during the disease course, which could be triggered by aggressive disease, infection, microbiota changes or medication compliance, among other. Cytomegalovirus (CMV) infection has been found to be more prevalent among IBD patients requiring hospitalization. The aim of this study is to compare the inpatient outcomes for patients admitted with an IBD flare with and without concomitant CMV infection.

METHODS:

This was a retrospective cohort study using the 2014 National Inpatient Sample, the largest publicly available inpatient database in the United States. Inclusion criteria were age older than 18 years and a primary ICD-9 CM code for any diagnosis of IBD flare. There were no exclusion criteria. The primary outcome was in-hospital mortality. The secondary outcomes were morbidity measured by intensive care unit (ICU) admission, shock, multi-organ dysfunction syndrome (MODS), malnutrition and need for partial/total colectomy, and resource utilization measured by length of hospital stay (LOS), total hospitalization charges, ultrasound (US), CT abdomen and colonoscopy need. Patients with IBD flare were classified as having or not CMV infection diagnosis using ICD-9 CM codes. Odds ratios and means were adjusted for the following confounders using multivariate regression analysis models: age, sex, race, median income in the patient's zip code, hospital region, rural location, size and hospital teaching status.

RESULTS:

90,920 patients with IBD flare were included in the study, from which 195 (0.21%) had a diagnosis of CMV infection. Mean age was 42.4 years and 53.5% of patients were female. The population was predominantly Caucasian (73%). The in-hospital mortality was higher among patients without CMV infection (0.28% vs 0%). On multivariate analysis, patients with CMV infection had higher risk of undergoing total/partial colectomy (OR 6.72, P < 0.01) and need for colonoscopy (OR 6.72, P = 0.01), with longer LOS and higher hospital charges (P < 0.01). There were no differences for other markers of morbidity or resource utilization. All adjusted odds ratios, adjusted means and P values are shown in Table 1.

CONCLUSION:

CMV coinfection in patients admitted to the hospital with IBD flare had higher odds of undergoing colectomy, while presenting higher hospitalization costs and length of stay. However, no impact in mortality was found in this specific group.
719 Utilization Analysis of a Treat to Target Approach for Inflammatory Bowel Disease: A Multi-Center Health Care System Review
Authors: Berkowitz Joshua , Becher Noah , Shah Samip , Swaminath Arun , Sultan Keith
Published: October 2019

INTRODUCTION:

A treat-to-target (TT) strategy, setting mucosal healing (MH) in inflammatory bowel diseases (IBD) as the desired treatment endpoint, is currently favored by experts. Advocates of this approach recommend the intensification of medical therapy to reach the goal of MH, even in patients who are in steroid free clinical remission. The utilization and practice of the TT strategy is unknown.

METHODS:

A retrospective chart review was performed for all IBD patients in the Northwell Health system to identify those in clinical remission who underwent colonoscopy between 01/01/2016 and 12/31/2018. Clinical remission at the time of colonoscopy was defined by a stable, steroid free IBD drug regimen and no IBD related surgery or hospitalization for 6 months prior. Patients in clinical remission but without MH reported on colonoscopy were defined as TT candidates. Demographic and treatment data were extracted from the medical record. We examined the frequency and type of TT utilization, defined as escalation of medical therapy within 1 month of the index colonoscopy. Analysis of variables associated with TT utilization was performed using the chi-square test.

RESULTS:

960 patients had a colonoscopy by 34 different gastroenterologists during the study period. 382 patients met criteria for clinical remission, 248 of whom had gross disease activity classifying them as TT candidates, Table 1. None of the 134 patients with MH had a change in their medication regimen within 1 month of colonoscopy. Among TT candidates 42 (16.93%) had utilization of TT during the 1 month follow-up. Patients utilizing TT were more likely to have no baseline medication use, 39.5% vs. 20.87 (P = 0.0102). There was decreased utilization of TT among those patients already using immunologic and/or biologic therapies, 21.42% vs. 38.88% (P = 0.03), Table 2. Patients utilizing vs. not utilizing TT where similar by age, gender, IBD type, and CD surgical history. For patients utilizing TT, strategies included initiation or modification of biologic therapy more commonly among CD vs. UC/indeterminate colitis patients, 64.29% vs. 10.71% (P = 0.0005). TT utilizing 5-ASA was more common for UC/indeterminate colitis vs. CD, 82.14% vs. 35.71% (P = 0.003), Table 3.

CONCLUSION:

We have demonstrated a low rate of TT utilization in our study population. When used, a TT strategy favoring biologic therapy was more common in CD. Further validation of TT, along with physician and patient education, will likely be needed if TT is to become widely adopted.
723 Evolution in Hospitalization and Outcomes of Patients With Inflammatory Bowel Disease: Nationwide Study From 1998-2014
Authors: Radadiya Dhruvil K. , Devani Kalpit H. , Charilaou Paris , Young Mark , Reddy Chakradhar
Published: October 2019

INTRODUCTION:

Approval of the first biologic agent by the FDA in 1998, revolutionized the management of inflammatory bowel disease (IBD). We hypothesized that this paradigm shift would improve outcomes amongst the hospitalized IBD patients. Hence we investigated the trends in the hospitalization of IBD patients and related outcomes using National database.

METHODS:

We queried the Nationwide inpatient sample (NIS) database from the year 1998 to 2014. Hospitalized adult patient with IBD, i.e., Crohn's disease (CD) or ulcerative colitis (UC), their outcomes and procedures (including surgeries), were identified using ICD-9-CM diagnosis and procedure codes. Trends were analyzed using Cochrane Armitage test for categorical variables and the nonparametric test for continuous variables. We calculated the national estimates using the discharge weights.

RESULTS:

Total of 3,876,583 patient with IBD were included in the study. The mean age of the study population was 57.8 years; females were 57.6% and 67.2% White. Baseline characteristics of the patients, hospital characteristics and insurance types are shown in Table 1. Hospitalization of the patient with IBD nearly doubled from 70/100,000 US adult population to 125/100,000 (Figure 1). Since 1998, inpatient mortality remained stable, with an overall mortality rate of 1.5%. Length of stay (LOS) decreased, a numerically small decrease from 6.2 to 5.5 days, while hospital charges increased from $14,771 to $47,548 (Figures 3 and 4). Prevalence of anemia and transfusion utilization increased to 28.6% and 9.2% respectively in 2014. Co-morbidities such as acute kidney injury (1.4% to 13.2%), venous thromboembolism (1.9% to 3.5%) and Clostridium difficile infection (1.4% to 5.2%) also increased along with hospitalization requiring ICU (1.6% to 3%). However, CD and UC related surgery decreased from 15.9% to 10.7% and 5.7% to 3.5% respectively. Utilization of inpatient lower endoscopy also declined from 23% to 13.1%. Table 2 shows trends in complication, outcomes, and resource utilization over the study period.

CONCLUSION:

Over 17 years, hospitalization of patients with IBD has increased. Mortality, perforation rate, colon cancer prevalence, and LOS remained steady with marginal changes numerically. However, hospitalization charges, along with other co-morbidities/complications related to IBD increased significantly even though utilization of endoscopy and surgery has declined.
725 Acute Vascular Insufficiency of the Intestines in Crohn's Disease: Insights From the Healthcare Utilization Project
Authors: Haq Khwaja F. , Kaur Randeep , Solanki Shantanu , Chandra Chakinala Raja , Iqbal Umair , Bhurwal Abhishek , Khan Zubair , Shah Harshil , Haq Khwaja S. , Burney Azam , Khan Muhammad Ali , Mishra Kajali , Patel Neil , Bhatti Faiza
Published: October 2019

INTRODUCTION:

Inflammatory bowel disease is associated with increased risk of mesenteric ischemia, likely due to factors such as vascular atherosclerosis caused by long-term inflammation, vasculitis, coagulation abnormalities, and abnormal lipid metabolism. Limited data exists for hospitalizations associated with acute vascular insufficiency of the intestines (AVII) in patients with Crohn's disease.

METHODS:

We analyzed the National Inpatient Sample (NIS) database for the years 2005-2011 to identify hospitalizations with Crohn's disease (ICD-9 CM code 555.0, 555.1, 555.2, and 555.9). Hospitalizations complicated by AVII (ICD-9 CM code 557.0) in this cohort were then identified. NIS is the largest all-payer inpatient care database in the United States, containing data on more than seven million hospital stays each year. Its large sample size is ideal for developing national and regional estimates and enables analyses of rare conditions, uncommon treatments, and special populations. Temporal trends of AVII in this cohort, patient demographics, comorbidity measures, and outcomes during the study period were determined using Cochran-Armitage trend test.

RESULTS:

Between 2005 and 2011, hospitalization with CD increased from 56,739 to 65,281 (P-trend < 0.0001, Figure 1a). The proportion of hospitalizations complicated by AVII increased from 0.14% in 2005 to 0.28% in 2011 (P-trend < 0.0001, Figure 1b). AVII was more common in women (57.9%) (P-trend = 0.0007, Figure 1c) and in Caucasians (64.7%). All-cause inpatient mortality increased from 6.3% to 7.6% (P = 0.001, Figure 1d). Analysis of the Agency for Healthcare Research and Quality (AHRQ) comorbidity measures revealed that hypertension, renal failure and psychiatric disorders were some of the most commonly associated comorbidities (Figure 2).

CONCLUSION:

A significant increase in the number of hospitalizations for CD complicated by AVII was seen during the study period. Caucasians and women were more commonly affected than other groups. There was also an increase in the in-hospital mortality associated with these hospitalizations. Although hypertension, renal failure and psychiatric disorders were more commonly associated with AVII in Crohn's disease hospitalizations, there were several other comorbidities including diabetes mellitus, obesity and chronic pulmonary disease that showed increasing trends. Further studies are needed to identify predictors of these trends and factors responsible for such outcomes to better elucidate and perhaps support our findings.
726 Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates in the Tofacitinib Ulcerative Colitis Clinical Program
Authors: Winthrop Kevin L. , Loftus Edward V. , Baumgart Daniel C. , Salese Leonardo , Thorpe Andrew J. , Lawendy Nervin , Chan Gary , Pedersen Ronald D. , Reinisch Walter
Published: October 2019

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Tofacitinib safety in patients (pts) with UC was evaluated in an 8-week induction Phase (P) 2 study (NCT00787202),
1
2 8-week induction P3 studies (OCTAVE Induction 1 & 2; NCT01465763 & NCT01458951),
2
a 52-week maintenance P3 study (NCT01458574), and an ongoing, open-label, long-term extension (OLE) study (OCTAVE Open, NCT01470612).
3
We present updated infections data (Sep 2018) from the tofacitinib UC clinical program.
4,5

METHODS:

Pts receiving placebo, tofacitinib 5 or 10 mg twice daily (BID) were analyzed as Induction (P2 & P3, n = 1220), Maintenance (P3, N = 592), and Overall (pts in P2, P3 & OLE receiving tofacitinib 5 or 10 mg BID, N = 1157 [Sep 2018]) Cohorts. Proportions and incidence rates (IRs; pts with events per 100 pt-years [PY] of exposure) were evaluated for infections of special interest (incl. serious infections [SIs], opportunistic infections [OIs; independently adjudicated], and herpes zoster [HZ]).

RESULTS:

A total of 1157 pts received ≥1 dose of tofacitinib 5 or 10 mg BID (83% predominantly 10 mg BID [avg. daily dose ≥15 mg]), with 2403.6 PY of exposure (median 623 days, up to 6.1 years of treatment). The Table 1 shows infection IRs by Cohort. In the Overall Cohort, nasopharyngitis was the most frequent infection. For SIs, the Overall Cohort “Tofacitinib All” IR (1.75 [95% CI 1.27, 2.36]) was similar to the Maintenance Cohort IRs for tofacitinib 5 and 10 mg BID. No SIs resulted in death. OIs were infrequent (28 pts) and most were HZ (24 pts; IR 0.99 [95% CI 0.63, 1.47]), mostly cutaneous. Not all HZ events were OIs; 83 pts overall had HZ events (IR 3.57 [95% CI 2.84, 4.43]; 6 serious).

CONCLUSION:

In induction, SIs and OIs occurred with tofacitinib but not with placebo. Overall, SIs were generally infrequent and Overall Cohort IRs did not suggest increased risk with longer tofacitinib treatment vs the Maintenance Cohort. Non-HZ OIs were rare. SI incidence was similar in the UC and rheumatoid arthritis programs (incl. increased HZ risk)
6
and to other UC therapies incl. biologics.
7
730 Safety, Pharmacokinetics, and Pharmacodynamics of the Novel Oral Peptide Therapeutic PN-10943 (alpha4beta7 Integrin Antagonist) in Normal Healthy Volunteers
Authors: Gupta Suneel K. , Cheng Xiaoli , Kanwar Bittoo , Matheakis Larry , Bhandari Ashok , Liu David , Shames Rich
Published: October 2019

INTRODUCTION:

Oral gut-restricted α4β7 integrin peptide antagonists represent a new therapeutic strategy for IBD. An example is PTG-100, which in a recent Phase 2 study was associated with higher rates of clinical and histologic remission relative to placebo in ulcerative colitis patients (Sandborn et al, UEGW 2018). PN-10943 is an oral, gut-restricted, potent, and highly selective α4β7 integrin antagonist peptide that has demonstrated preclinical superiority to PTG-100 (Mattheakis et al, DDW 2019). The purpose of this first-in-human Phase 1 study with PN-10943 was to assess safety, tolerability, PK, and PD activity in NHV and confirm previous preclinical observations.

METHODS:

A randomized, placebo-controlled Phase 1 trial of single (SAD) and multiple (MAD) ascending doses of PN-10943 was conducted in 70 male NHV. MAD regimen consisted of 14 daily doses. Subjects are monitored for safety and tolerability while undergoing serial plasma PK and blood PD evaluations as measured by integrin receptor occupancy (RO) and expression (RE) on circulating α4β7+ lymphocyte subsets.

RESULTS:

In the SAD portion of the study, 100, 300, 1000, and 1400 mg cohorts were dosed with no serious adverse events or dose-limiting toxicities. All adverse events were of mild to moderate severity and resolved without complication. In the MAD portion of the study doses studied were 100, 300, & 1000 mg for 14 days. Peak plasma concentration (Cmax) and area under the curve increased in a dose proportional manner and plasma pharmacokinetics were also time invariant between day 1 and day 14 in the MAD cohort. There was a significant dose dependent increase in RO of blood memory T cells (reaching >90% in the 1000 mg cohort). RE of α4β7 on blood memory T cells decreased in a dose dependent manner consistent with α4β7 internalization. The PD responses strongly correlated with plasma Cmax, and the binding activity from subject/time-matched RO on α4β7 memory T cells was comparable to that demonstrated in preclinical studies.

CONCLUSION:

Following oral administration in NHV, PN-10943 was well tolerated. As expected, plasma exposure was very low, and there was significant dose-related PD. The Phase 1 PK/PD relationship confirms previous preclinical observations in which PN-10943 demonstrated superiority to PTG-100. These Phase 1 PD data for PN-10943 together with the previous clinical activity of PTG-100 suggest that PN-10943 may potentially be an effective oral therapy for the treatment of UC.