bluuebunny/crossref_metadata_2025_split huggingface dataset:
706 Impact of Baseline Corticosteroid Therapy on Tofacitinib Induction Efficacy and Infection Risk in Patients With Ulcerative Colitis: Data From Global Clinical Trials
Authors: Lichtenstein Gary R. , Cohen Benjamin L. , Salese Leonardo , Soonasra Arif , Modesto Irene , Wang Wenjin , Woodworth Deborah A. , Chan Gary , Quirk Daniel , Su Chinyu , Peyrin-Biroulet Laurent 
Published: October 2019

INTRODUCTION:
Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Oral corticosteroids (CS) can be used as induction therapy, but side effects are a concern.
1

METHODS:
We evaluated efficacy and infection risk with tofacitinib 10 mg twice daily (BID) based on baseline CS use in UC induction studies. Remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore 0), mucosal healing (Mayo endoscopic subscore ≤1) and clinical response (decrease from baseline total Mayo score of ≥3 points and ≥30%, and decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of 0 or 1) were evaluated in the 8-week, Phase 3 tofacitinib OCTAVE Induction 1 & 2 studies (NCT01465763 & NCT01458951; pooled data). Induction studies allowed stably dosed CS (25 mg/day maximum). Efficacy and safety data were summarized by oral CS use at induction baseline (BLC-Yes/No). Infections of interest included herpes zoster (HZ), serious infections (SIs), and adjudicated opportunistic infections (OIs).

RESULTS:
Of 1139 patients (pts) (placebo [PBO]: n = 234; 10 mg BID: n = 905) in OCTAVE Induction 1 & 2, 525 (46.1%) were on CS at baseline (<15 mg daily dose: 32.8%; ≥15 mg daily dose: 67.2%). A statistically significant treatment effect of tofacitinib 10 mg BID vs PBO was observed for remission, mucosal healing, and clinical response at Week 8, for both subgroups of pts with and without baseline oral CS use (Table 1). Differences vs PBO were numerically greater for pts not receiving oral CS at baseline. In OCTAVE Induction 1 & 2, infections of interest occurred with similar frequency among both subgroups of pts: the proportion of PBO-treated pts with HZ was 0.8% for BLC-No vs 0.0% for BLC-Yes; and 0.2% for BLC-No vs 1.0% for BLC-Yes with 10 mg BID. The proportion of PBO-treated pts with SIs was 0.0% for BLC-No vs 0.0% for BLC-Yes; and 1.0% for BLC-No vs 0.2% for BLC-Yes with 10 mg BID. The proportion of PBO-treated pts with OIs was 0.0% for BLC-No vs 0.0% for BLC-Yes; and 0.2% for BLC-No vs 0.5% for BLC-Yes with 10 mg BID.

CONCLUSION:
Tofacitinib demonstrated significant induction efficacy vs PBO for both subgroups of pts with and without baseline CS use. Proportions of HZ, SIs, and OIs in OCTAVE Induction 1 & 2 were generally similar for both subgroups of pts. The relatively small number of events and short duration of follow-up (8 weeks) are limitations.
713 A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of a Targeted Release Oral Cyclosporine Formulation in the Treatment of Mild to Moderate Ulcerative Colitis: Influence of Immunosuppressants at Baseline
Authors: Bloom Stuart , Iqbal Tariq , Nwokolo Chuka , Jairath Vipul , Hall Jesse , Dzyngel Bruce , Gardzinski Peter 
Published: October 2019

INTRODUCTION:
Patients (pts) with ulcerative colitis (UC) who have failed immunosuppressants (IM) and biologics have demonstrated poorer response to subsequent therapies.
1
Cyclosporine (CsA) could be an alternative option since it has similar efficacy and safety to infliximab for severe UC,
2
but its use is limited due to concerns regarding systemic toxicity. ST-0529 is a novel oral formulation of CsA that delivers the drug directly to the colon, allowing for precise targeting of the diseased tissue while potentially limiting the risk of systemic toxicity.

METHODS:
A phase IIa study was conducted in a total of 118 subjects with baseline Disease Activity Index (DAI) < 6 (mild UC) or ≥6 (moderate UC), randomized 1:1 to receive 75 mg ST-0529 once daily (n = 53) or placebo (n = 65) for 4 weeks. The primary endpoint was the induction of clinical remission (DAI score ≤2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary endpoints were safety and tolerability, mucosal healing, clinical response, and histological healing.
3,4
Post-hoc subgroup analysis was conducted in 93 subjects with moderate UC, of whom 75 received at baseline 5-ASA alone or in combination (n = 51, with/without steroids; n = 24, with/without IM) to evaluate the impact of them on clinical improvement (DAI reduction ≥3) and composite subscores (rectal bleeding and stool frequency with or without mucosal appearance evaluation).

RESULTS:

Table 1 shows the influence of baseline medications on the improvement of DAI scores in subjects with moderate UC, and Tables 2 and 3, the impact of IM on the analyzed parameters. Safety was balanced for the overall population.

CONCLUSION:
This analysis showed that clinical improvement and composite subscores were influenced by baseline medication in pts with moderate UC. The poorer response in the IM treated group was potentially a function of severity or refractory disease and/or concomitant use of UC medication (prednisone < 10 mg/day, 5-ASAs or purine analogues) at baseline. Concomitant UC medications were not restricted at study entry as long as pts maintained stable dosing regimens throughout. These preliminary data support further investigation of ST-0529 usage as a twice daily treatment for the induction and maintenance of remission in UC pts with moderate disease, which will be the focus of the phase IIb trial.
738 Current Treatment Patterns Among Patients With IBD in the U.S. Initiating Biologic Therapy
Authors: Bornheimer Rebecca , Hass Steve , Nag Arpita , Oster Gerry 
Published: October 2019

INTRODUCTION:
Treatment options for inflammatory bowel disease (IBD: Crohn's disease [CD] and ulcerative colitis [UC]) now include targeted therapies such as tumor necrosis factor (TNF) inhibitors and integrin receptor antagonists. With increasing therapeutic options, it is crucial to understand clinical use of these agents. This study reports on the current pattern and duration of biologic use in patients with IBD.

METHODS:
Adults (≥18 years) with CD or UC who initiated treatment with biologics between January 1, 2012 and December 31, 2016 were identified using the IQVIATM Real-World Data Adjudicated Claims Database – US. Treatment episode duration was defined as time from first (index date) to final receipt, identified based on a ≥90-day gap in therapy, surgery for IBD, or therapy switching, whichever came first. In patients with CD or UC who had ≥2 claims for biologics, we examined length of treatment episodes by product as well as for biologics overall. Kaplan–Meier (KM) methods were used.

RESULTS:
We identified a total of 18,140 and 11,474 patients with CD and UC, respectively, who began treatment with a biologic for IBD during the study period and had not received a biologic prior to January 1, 2012. Over an average follow-up of 22.9 months, the mean duration of biologic treatment was 13.5 months (CD: 13.7; UC: 13.1). After 12 and 24 months of treatment, 7.0% (CD: 7.2%; UC: 6.8%) and 11.0% (CD: 11.2%; UC: 10.6%) of patients beginning biologic therapy had undergone surgery for IBD, respectively. The number of patients beginning treatment with individual biologics is presented in Figure 1. Among patients starting treatment with adalimumab or infliximab, ∼10% had previously received another biologic during the 6-month period prior to index date for that biologic, compared with ∼30–40% of patients starting treatment with other biologics. The mean duration of treatment with adalimumab or infliximab was 12.2 months. Treatment episodes were shorter for other biologics (shortest duration: 4.8 months for patients with CD beginning ustekinumab). By month 6 of treatment, KM estimates of the percentage of patients with CD starting another IBD biologic ranged from 4.1% (ustekinumab) to 8.1% (certolizumab); for UC, the range was 3.6% (vedolizumab) to 15.9% (golimumab).

CONCLUSION:
Most patients starting biologic therapy have no evidence of prior receipt of IBD-related biologics. Duration of biologic treatment for IBD averages approximately 1 year for adalimumab and infliximab but is shorter for other agents.
741 Low Serum Levels of IgG4 Antibodies May Function as a Biomarker of Severity in Inflammatory Bowel Disease
Authors: Koutroumpakis Filippos , Philipps Anna E. , Yadav Dhiraj , Rivers Claudia Ramos , Schwartz Marc , Proksell Siobhan , Johnston Elyse , Dueker Jeffrey , Hashash Jana G. , Barrie Arthur , Harrison Janet , Din Hassieb , Babichenko Dmitriy , Tang Gong , Binion David 
Published: October 2019

INTRODUCTION:
Immunoglobulin G subclass 4 (IgG4) is hypothesized to play an immunoregulatory role which effectively decreases humoral immune responses. The presence of high serum IgG4 levels is considered a biomarker for IgG4 related diseases. On the other hand, low levels of IgG4 have been reported mainly in infectious diseases but also in healthy individuals. The role of abnormal serum IgG4 in inflammatory bowel disease (IBD) has not been fully characterized. We sought to define alterations in serum IgG4 in IBD patients and its association with multiyear disease severity.

METHODS:
We analyzed a prospective, longitudinal IBD registry of consented patients followed at a tertiary center over a 10-year time period. IBD patients with IgG4 serum levels available formed the study population. Demographics and multiyear clinical data were collected and analyzed. Disease severity was approximated with patterns of healthcare utilization metadata. We compared IBD patients with low, normal or high serum IgG4 levels.

RESULTS:
There were 1213 IBD patients with IgG4 levels tested [females 54%, Crohn Disease (CD) 65%, Ulcerative Colitis (UC) 33%, IBD unclassified 2%, median age at diagnosis 25 years]. Low IgG4 levels were seen in 245 patients (20%) and elevated IgG4 levels occurred in 65 (5%). In univariate analysis, low IgG4 was associated with CD (P = 0.028) and lifetime IBD surgeries (P < 0.001). During the 10-year observation period, low IgG4 patients had higher rates of new IBD surgeries (P = 0.012), office visits (P = 0.007), requirement for biologic agents (P = 0.009), steroid use (P = 0.021) and higher cumulative healthcare charges (P = 0.015) compared with normal IgG4 patients. In the multivariate analysis (MVA), low IgG4 was associated with IBD surgeries (P = 0.003) and requirement for biologic therapy (P = 0.017) during the 10-year period as well as higher rates of lifetime IBD surgery (P = 0.002). High IgG4 levels were associated with younger age (P = 0.006), male gender (P < 0.001) and lower steroid use (P = 0.043) (univariate analysis) but were not associated with primary sclerosing cholangitis (P = 0.112); in MVA only male gender (P = 0.001) remained significant.

CONCLUSION:
Low IgG4 is four times more common than IgG4 elevation in IBD and is associated with multiple markers of disease severity. Further investigation is required to determine whether this finding represents the loss of a potential anti-inflammatory molecular mechanism which contributes to more severe illness in IBD.
742 Quality Improvement in IBD Care: The Influence of a QI Specific Conference for Fellows
Authors: Afolabi Olayinka , Faber Alexis , Kutaimy Raya , Naylor Paul , Ehrinpreis Murray N. 
Published: October 2019

INTRODUCTION:
Given the complexity of management of inflammatory bowel disease (IBD), medical societies such as the American Gastroenterological Association (AGA) and Crohn's and Colitis Foundation of America (CCFA) have established measures aimed at defining quality of care. In 2011, the AGA proposed 10 quality metrics for IBD, eight of these measures relate to outpatient management and two focus on inpatient management. Our objective was to evaluate compliance with these measures in our own general GI practice and determine whether a GI conference discussing quality improvement (QI) in 2017 was effective.

METHODS:
The 8 AGA IBD core measures related to the outpatient management of IBD were assessed. From a list of patients with ICD-9 codes for IBD, We identified 104 patients with well documented Crohn's disease (CD) or ulcerative colitis (UC) and multiple visits through 2018. For this quality assessment, we used the most recent GI visit and. The patients were divided into two groups (most recent visit prior (Pre) or after (Post) a GI conference in 2017. Significant differences were defined using student's t-test or Pierson Chi-square.

RESULTS:
There were 40 patients in the pre group and 64 patients in the post group. The gender and racial distribution were not significantly different between pre and post (70% pre vs 61% post female; 75% vs 73% AA). There were more CD patients in the post group (48% vs 70% P < 0.05) and more patients were on an anti-TNF biologics (18% vs 41%). Table 1 details the results of the quality measures before and after the QI conference. Prior to the QI conference in 2017, there were areas for improvement (i.e., <75% compliance) in 4 of the categories Bone density screening, screening for Vit D deficiency, documenting disease severity, vaccinations and tobacco cessation counseling (Table 1). Following the QI conference discussion in 2017, there was good improvement seen several areas. Although, there were small improvements in vaccinations, the numbers are still very low.

CONCLUSION:
We demonstrated improved compliance with the AGA IBD quality metrics after the QI conference, though there are still areas of improvement for documenting immunizations and tobacco cessation counselling. To help improve compliance with core measures, we propose advocating for our current EMR systems to have the ability to trigger alerts regarding specific measures and improve compliance as well as educating new fellows on proper documentation and standardization of the AGA IBD quality metrics.
750 Incidence and Risk Factors of Constipation in Inflammatory Bowel Disease Patients During Remission
Authors: Tabbaa Mumtaz , Tunzi Matthew 
Published: October 2019

INTRODUCTION:
The incidence of constipation in long term follow-up of chronic IBD patients during remission hasn't been studied. Though constipation was observed in patients with proctitis, and hard stools reported in 27% of patients with active UC (1), constipation was not the focus of IBD studies in the past. The overlap of IBS with IBD was studied, a small and similar incidence of constipation was reported in both groups (2). This five-year follow-up study documented the incidence of constipation in IBD patients during remission, analyzing the risk factors related to the IBD Illness.

METHODS:
259 Patients with IBD in the GI clinic were followed for 5 years, between 2013-2018. Patients who developed constipation during the remission period were studied to find the incidence of constipation and risk factors related to IBD. The remission was identified as clinical remission for more than 6 mo, or by endoscopic or histologic remission. All patients had KUB documented the high fecal load without obstruction at the time of clinical presentation with constipation. Factors related to IBD illness were analyzed, including gender, type of IBD, period of illness, and intestinal involvement. Those with Proctitis only and those with previous surgeries were extracted.

RESULTS:
89/259 patients (34%) developed constipation. 43/89 with UC vs 41/89 with CD (P > 0.1). No statistical significance also found for the gender (54M Vs 35F) and the period of the illness (52 < 5 years, vs 37 > 5 years). The involvement of the distal colon including pancolitis involvement was significantly higher than the involvement of the right side of the colon (67/89 had distal involvement vs 3/89 proximal involvement), to the point of statistical significance (P < 0.05). Patients with skipping lesions with distal involvement were 19/89.

CONCLUSION:
This study showed a high incidence of constipation in patients with inactive IBD (34%), it was higher than the incidence of patients with hard stools at the time of diagnosis (4/50). The clinical setting of this study with long term observation was different from the clinical setting of the 2 surveillance that reported constipation in IBD patients in the medical literature. Though constipation is a functional symptom, the risk factor of IBD involvement is not related to the IBS. The successful treatment of constipation in this group impacted the quality of life and the management of IBD with medications, only 3 patients in this group required treatment with immunosuppressive or biologic medications.
755 Histology and Endoscopy Discordance in Inflammatory Bowel Disease Varies by Phenotype and Location of Disease
Authors: Serigado Soares Da Costa Joao M. , Quintero Maria A. , Koru-Sengul Tulay , Poveda Julio , Damas Oriana , Deshpande Amar , Kerman David , Abreu Maria T. 
Published: October 2019

INTRODUCTION:
Mucosal healing is currently the ultimate target in the treatment of inflammatory bowel disease (IBD). It has become increasingly evident that mucosal healing assessed during endoscopy may not imply histological healing. It is important to define which patients are more likely to have underlying microscopic inflammation in the setting of a normal appearing mucosa in order to tailor treatment approaches and minimize unnecessary biopsies.

METHODS:
Patients were included if they have a diagnosis of either Crohn's or ulcerative colitis, based on standard criteria and had provided consent to have clinical data and tissue collected as part of our IRB-approved IBD biorepository. Endoscopies were performed as part of routine clinical care and biopsies taken and endoscopy findings recorded in a protocolized fashion. The endoscopist rated each area biopsied as “no inflammation,” “mild,” “moderate” and “severe” inflammation. Clinical pathology results were reviewed from the matching endoscopic area. Multiple univariate and multivariate analyses with ordinal logistic regression were used to examine the relationship of endoscopic and histologic scores.

RESULTS:
There is an association between inflammation on endoscopy and inflammation on biopsy (OR, 2.97; 95% CI, 2.75-3.18; P < 0.0001). There is an incremental effect of the probability of having an inflamed biopsy as the degree of inflammation on endoscopy increases (mild inflammation OR, 2.50; P < 0.0001; moderate OR 4.28; P < 0.0001; severe OR 4.81; P < 0.0001). A subgroup of patients had normal appearing endoscopies but inflamed biopsies (9% of the sample). Sub group analysis revealed that biopsies taken from the neo-terminal ileum compared to native terminal ileum were two times more likely to be discordant on histology (OR 2.01; 95% CI, 1.27-3.16; P = 0.0027).

CONCLUSION:
The treatment goal for patients with IBD is mucosal healing. The definition of mucosal healing varies and encompasses both macroscopic and microscopic healing. We describe an overall good correlation between endoscopic inflammation and histologic inflammation. These findings are important as they may lead to a decrease in the number of biopsies taken in endoscopically normal appearing tissues. Interestingly, the neo-TI in CD patients was most frequently discordant with normal appearing endoscopy yet inflammation microscopically. Longer follow up studies are needed to determine whether patients with microscopically inflamed neo-TI have a worse outcome than those without inflammation.
756 Novel Risk Factors and Outcomes in Inflammatory Bowel Disease Patients With Clostridium difficile Infection
Authors: Voth Elida , Solanky Dipesh , Loftus Edward V. , Pardi Darrell , Khanna Sahil 
Published: October 2019

INTRODUCTION:
Patients with inflammatory bowel disease (IBD) are at significantly increased risk for Clostridium difficile infection (CDI). CDI in IBD is associated with increased in-hospital mortality, IBD treatment failure, re-hospitalization and high CDI recurrence rates. The existing literature on predictors of these adverse outcomes is limited. We evaluated four potentially modifiable novel risk factors (BMI, statin use, opioid use, and antidepressant use) on the risk and outcomes of CDI in patients with IBD.

METHODS:
CDI disease severity and other clinical outcomes, including colon surgery, CDI recurrence, CDI-related hospitalization, IBD exacerbations, and mortality were abstracted using the electronic medical record. Additionally, variables including BMI, statin use, opioid use, and antidepressant use at the time of CDI were abstracted from records for patients with IBD and CDI from 2008 and 2013. Statistical analysis comprised of descriptive statistics and univariate and multivariate logistic regression analyses.

RESULTS:
There were 137 patients with IBD and CDI included in this study: 70 with ulcerative colitis (51%), 63 with Crohn's disease (46%), and 4 with indeterminate colitis (3%). The median age was 46 years, and 55% were female. On multivariate analysis controlling for age, 43% of patients in the overweight BMI category had severe or severe complicated CDI, compared to 22% of patients in the underweight/normal BMI (OR, 2.85, P = 0.02) and 19% in the obese category (OR, 3.95, P = 0.04). Statin use was associated with severe or severe complicated CDI when controlling for age and BMI (OR, 5.66, P = 0.01). On multivariate analysis controlling for age and CDI severity, there was no association between statin use and post-CDI IBD exacerbations. Opioid and antidepressant use were not associated with CDI disease severity or IBD exacerbations. BMI category, statin use, opioid use, and antidepressant use were not associated with colon surgery, CDI recurrence, CDI-related hospitalizations, or mortality at 1 year.

CONCLUSION:
An overweight BMI and statin use were associated with severe or severe complicated CDI. There was no association between statin use and IBD exacerbations following CDI. Opioid and antidepressant use were not associated with disease severity or frequency of IBD exacerbations following CDI. Further studies are needed to better understand how these results could impact management of patients with IBD to improve clinical outcomes and potentially reduce the risk of CDI.