Immunomodulatory Agents for Treatment of Patients with Inflammatory Bowel Disease (Review safety of anti-TNF, Anti-Integrin, Anti IL-12/23, JAK Inhibition, Sphingosine 1-Phosphate Receptor Modulator, Azathioprine / 6-MP and Methotrexate)
PURPOSE OF THE REVIEW/OBJECTIVE:As treatment options for Inflammatory Bowel Disease (IBD) expand each class of medication will have specific safety concerns and side-effect profiles that need to be considered for optimal treatment of patients. We will review the most recent safety data for the newly approved immunomodulator therapies for the treatment of IBD. RECENT FINDINGS/RESULTS:There are a growing number of publications outlining safety concerns for medications used to treat IBD. We reviewed safety profile of anti-tumor necrosis factor antibodies (TNF) with specific attention to combination therapy (anti-TNF plus immunomodulator). Recent publications have demonstrated increased risk of serious infection and malignancy (lymphoma and overall cancer rates) in patients receiving anti-TNF combination therapy when compared with patients receiving anti-TNF monotherapy or immunomodulator monotherapy. Recent publications on Janus Kinase Inhibitors indicate an increased risk of infection, specifically Herpes Zoster, and increased risk of major cardiovascular events and venous thromboembolic events resulting in a black box warning for the medication. In contrast, anti-interleukin 12/23 agents and gut selective anti-integrin antibody agents have demonstrated a favorable side-effect profile with low rates of infection and malignancy. The latest class of medications to be approved, sphingosine 1-phosphate (S1P) receptor modulators, have cardiac and infectious precautions. The field of IBD treatment is rapidly evolving with several mechanistic classes of medications now available. While corticosteroids continue to be associated with the greatest, overall, safety risks, each of the newer mechanistic classes have unique safety concerns. In the future, as we gain more experience with these agents, we will need to continue to evaluate the safety profile of our therapies used alone or in combination to make informed treatment decisions with our patients.
Implementation of an Inpatient IBD Service Is Associated with Improvement in Quality of Care and Long-Term Outcomes
BACKGROUND:There is wide variation in the quality of care of hospitalized patients with inflammatory bowel disease (IBD). Prior studies have demonstrated that a specialized inpatient IBD service improves short-term outcomes. In this study, we assessed the impact of a dedicated IBD service on the quality of care and long-term outcomes. METHODS:This retrospective cohort study included adult patients admitted for a complication of IBD between March 2017 and February 2019 to a tertiary referral center. In March 2018, a dedicated inpatient IBD service co-managed by IBD gastroenterologists and colorectal surgeons was implemented. Quality of care outcomes included C. difficile stool testing, confirmed VTE prophylaxis administration and opiate avoidance. Long-term outcomes were clinical remission, IBD-related surgery, ED visits, and hospital readmissions at 90 days and 12 months. RESULTS:In total, 143 patients were included; 66 pre- and 77 post-implementation of the IBD service. Fifty-two percent had ulcerative colitis and 48% had Crohn's disease. After implementation, there was improvement in C.difficile testing (90% vs. 76%, Pâ€‰=â€‰0.04), early VTE prophylaxis (92% vs. 77%, Pâ€‰=â€‰0.01) and decreases in narcotic use (14% vs. 30%, Pâ€‰=â€‰0.02), IBD-related ED visits at 90Â days (7% vs 18%, Pâ€‰=â€‰0.03) and 12Â months (16% vs 30%, Pâ€‰=â€‰0.04), and IBD readmissions at 90Â days (16% vs. 30%, Pâ€‰=â€‰0.04). There were no differences in rates of clinical remission or surgery. CONCLUSIONS:The creation of a dedicated inpatient IBD service improved quality of IBD care and reduced post-discharge ED visits and readmissions and broader implementation of this strategy may help optimize care of hospitalized IBD patients.
Health Maintenance Consensus for Adults With Inflammatory Bowel Disease
BACKGROUND:With the management of inflammatory bowel disease (IBD) becoming increasingly complex, incorporating preventive care health maintenance measures can be challenging. The aim of developing these updated recommendations is to provide more specific details to facilitate their use into a busy clinical practice setting. METHOD:Fifteen statements were formulated with recommendations regarding the target, timing, and frequency of the health maintenance interventions in patients with IBD. We used a modified Delphi method and a literature review to establish a consensus among the panel of experts. The appropriateness of each health maintenance statement was rated on a scale of 1 to 5 (1-2 as inappropriate, and 4-5 as appropriate) by each panelist. Interventions were considered appropriate, and statements were accepted if â‰¥80% of the panelists agreed with a score â‰¥4. RESULTS:The panel approved 15 health maintenance recommendations for adults with IBD based on the current literature and expert opinion. These recommendations include explicit details regarding specific screening tools, timing of screening, and vaccinations for adults with IBD. CONCLUSIONS:Patients with IBD are at an increased risk for infections, malignancies, and other comorbidities. Given the complexity of caring for patients with IBD, this focused list of recommendations can be easily incorporated in to clinical care to help eliminate the gap in preventative care for patients with IBD.
Using objective structured clinical examinations to assess trainee telehealth performance measures in ibd: A pilot program [Meeting Abstract]
Introduction: The objective structured clinical examination (OSCE) is a common educational strategy to assess interpersonal skills and knowledge gaps, and we have previously shown its benefits in inflammatory bowel disease (IBD) education. As a result of the COVID-19 pandemic, there has been explosive growth in telehealth. Currently, we lack methods to teach and evaluate trainees' related skillset and no telehealth-specific milestones exist. We assessed the telehealth proficiency of gastroenterology (GI) fellows as part of an annual IBD OSCE over Zoom (Z-OSCE).
Method(s): Seven GI fellows from four programs participated in Z-OSCE featuring four clinical scenarios. We used previously validated OSCE checklists to assess the fellows' performance in IBDspecific cases. Telehealth communication skills were also assessed. One of the scenarios required the trainees to conduct a televisit focusing on preventative care for a Crohn's disease patient based on the ACG guideline. Checklists were scored on a 3-point Likert scale by the Standardized Patient (SP).
Result(s): The telehealth behavioral anchored checklist items included: maintaining proper computer etiquette, use of non-verbal communication and positioning to optimize the encounter, optimized technical aspects, and exhibiting comfort and confidence with the virtual platform. In these domains 5 or 6 (out of 7) fellows received 3 points. In contrast less than half of the fellows asked questions of the SP to make sure they understood or acknowledged emotion, and 3 out 7 fellows did not make appropriate eye contact. Despite high performance in the telehealth aspects of the encounter, the SP did not fully recommend fellows for their communication skills without reservations to friends/ family, with all fellows receiving 2 points.
Conclusion(s): Telehealth has quickly become a fixture of our profession, and merits educational opportunities and assessment to improve clinicians' competency, as it will likely outlast the COVID- 19 pandemic. To our knowledge, this is the first OSCE designed to assess telehealth performance in the delivery of IBD care. Z-OSCEs can play a unique role in simulating realistic telehealth visits and this pilot program helps us identify future educational needs. Assessment of fellows' performance during this virtual program can provide an opportunity for learning, growth and reflection as well as prepare trainees for future patient encounters
Virtual pivot: gastroenterology fellows' perception of a teleconferencing platform to conduct objective structured clinical examinations [Meeting Abstract]
Introduction: The objective structured clinical examination (OSCE) has been shown to not only assess but also improve the performance of trainees. Our group has previously demonstrated the benefits of OSCEs to assess gastroenterology (GI) fellows. We have successfully assessed performance across numerous milestones. Typically, OSCEs are held in person, however the COVID-19 pandemic has precipitated the need for virtual learning. We accordingly transitioned to a virtual zoom OSCE (Z-OSCE) and evaluated trainees' perception of this program.
Method(s): Fourteen first- and second-year GI fellows from five programs across multiple states participated in a four-station virtual OSCE on Zoom. Afterwards, participants answered a survey to share their perspectives and provide feedback. Learners were asked to rate the usefulness of the virtual OSCE and compare it to other in-person and virtual educational modalities. These questions were rated on a 10-point Likert scale (Figure 1). Additionally, free-text responses regarding any aspect of the OSCE were evaluated for comments on the virtual format.
Result(s): In comparing the usefulness of the virtual OSCE to other in-person modalities, trainees rated it a mean of 7.15 (range 5-10), and 31% of respondents rated it a 9 or 10. Trainees rated the virtual OSCE compared to other virtual learning modalities a mean of 8.15 (range 5-10), and 43% rated it 9 or 10. When asked whether they would recommend this OSCE as a training tool, the trainees gave a mean recommendation of 7.77 (range 5-10), and 38% gave a 9 or 10. General feedback regarding the nature of the OSCE noted the virtual format worked well, orientation to the format was important and could be improved by providing it in an email beforehand.
Conclusion(s): Virtual learning has been necessary during the COVID-19 pandemic, and it is crucial to evaluate the value of the novel Z-OSCE. Participants found the virtual OSCE may be more useful than in-person learning modalities and it compared favorably to other virtual learning modalities. One benefit of this modality was the easier inclusion of fellows from geographically disparate areas negating the need to travel for this program, a benefit given lack of universal access to simulation using standardized patients. To improve future exams, orientation prior to the day of the OSCE may improve trainees' experiences.
Ustekinumab Does Not Increase Risk of Adverse Events: A Meta-Analysis of Randomized Controlled Trials
GOALS AND BACKGROUND/OBJECTIVE:Ustekinumab (UST) is a monoclonal antibody inhibitor of IL-12/IL-23 approved for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We conducted a meta-analysis to compare rates of adverse events (AEs) in randomized controlled trials (RCTs) of UST for all indications. STUDY/METHODS:A systematic search was performed of MEDLINE, Embase, and PubMed databases through November 2019. Study inclusion included RCTs comparing UST to placebo or other biologics in patients aged 18Â years or older with a diagnosis of an autoimmune condition. RESULTS:Thirty RCTs with 16,068 patients were included in our analysis. Nine thousand six hundred and twenty-six subjects were included in the UST vs placebo analysis. There was no significant difference in serious or mild/moderate AEs between UST and placebo with an OR of 0.83 (95% CI 0.66, 1.05) and 1.08 (95% CI 0.99, 1.18), respectively, over a median follow-up time of 16Â weeks. In a sub-analysis of CD and UC trials, no difference in serious or mild/moderate AEs in UST versus placebo was seen. CONCLUSIONS:UST was not associated with an increase in short-term risk of AEs.
From the American Epicenter: Coronavirus Disease 2019 in Patients with Inflammatory Bowel Disease in the New York City Metropolitan Area
BACKGROUND:We aimed to characterize patients with inflammatory bowel disease (IBD) and novel coronavirus disease 2019 (COVID-19). METHODS:We performed a case series of patients with IBD and confirmed or highly suspected COVID-19 to assess rates of severe outcomes. RESULTS:We identified 83 patients with IBD with confirmed (54%) or highly suspected (46%) COVID-19. The overall hospitalization rate was 6%, generally comprising patients with active Crohn's disease or older men with comorbidities, and 1 patient expired. DISCUSSION/CONCLUSIONS:In this series of patients with IBD, severe outcomes of COVID-19 were rare and comparable to similarly aged individuals in the general population.
Real-World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis from 2 Tertiary IBD Centers in the United States
Background: Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on real-world outcomes are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from 2 US tertiary inflammatory bowel disease centers. Methods: Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Health (New York, New York) and University of Chicago Medical Center (Chicago, Illinois) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of â‰¤2, with a combined rectal bleeding and stool frequency subscore of â‰¤1. Results: Sixty-six UC patients were included. Ninety-two percent of patients had prior exposure to biologics or tofacitinib. Forty-three percent and 45% of patients achieved clinical remission by 3 and 12 months, respectively. Anti-TNF nonresponse and endoscopic Mayo score of 3 were negative predictors of clinical remission. Thirty-three percent of those followed for a year achieved concurrent endoscopic and histologic healing, which was significantly associated with lower partial Mayo score (P < 0.01) and lower stool frequency (P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis). Conclusions: In this cohort of mostly biologic-refractory UC patients, treatment with ustekinumab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials.
Inflammatory Bowel Disease Is Not Associated with Severe Outcomes of COVID-19: A Cohort Study from the United States Epicenter [Meeting Abstract]
INTRODUCTION: The outbreak of novel severe acute respiratory virus syndrome coronavirus 2 (SARS-CoV 2), the causative virus of coronavirus disease 2019 (COVID-19), has become a global pandemic. In the United States, cases exceed 2 million, with the New York City (NYC) metropolitan area at the epicenter. Patients with inflammatory bowel disease (IBD) are generally considered higher risk of infection due to immunosuppressive therapies, however, data are lacking regarding outcomes of COVID-19 in patients with IBD compared to the general population. We aim to investigate the impact of IBD on COVID-19 outcomes.
METHOD(S): We prospectively collected data on all patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] with confirmed or highly suspected COVID-19 (fever and/or close contact plus respiratory symptoms) and all non-IBD patients with confirmed COVID-19 from March 3 to May 10, 2020 at an academic medical center in NYC. Patient demographics, co-morbidities, and medication history were recorded. The endpoints were severe outcomes of COVID-19, including hospitalization, ventilator requirement, ICU admission and death. Adjusted analyses were performed for predictors of a composite endpoint of ventilator, ICU and death.
RESULT(S): We identified 83 patients with IBD [CD (n = 56, 67%) or UC (n = 27, 33%)] with confirmed or suspected COVID-19 and 8277 non-IBD patients with confirmed COVID-19 (Table 1). IBD patients had a lower median age (34 vs. 53 years; P < 0.001) and a higher proportion of Caucasians (69% vs. 41%; P < 0.001). IBD patients were less likely to have any co-morbidity (29% vs. 52%; P < 0.001), and had higher rates of immunomodulator (IMM) or biologic use. IBD patients with confirmed COVID-19 had lower rates of hospitalizations (14% vs. 51%; P < 0.001) and ICU admissions (2% vs. 13%; P = 0.04; Table 2). On multivariable analysis restricted to confirmed COVID-19, the presence of IBD was not associated with severe outcomes (OR 0.55, 95% CI 0.12-2.44, P = 0.43). Age, male gender, number of comorbidities, thiopurine and steroid use were significant predictors of severe COVID-19 outcomes, while TNF-antagonists had a protective effect (Table 3).
CONCLUSION(S): In this large cohort study, IBD was not a risk factor for severe outcomes of COVID-19. Age, co-morbidities, and exposure to thiopurines and steroids were associated with severe outcomes of COVID-19. TNF-antagonists may be protective from severe outcomes of COVID-19, but this requires further study
Real World Effectiveness and Safety of Ustekinumab for Ulcerative Colitis from Two Tertiary IBD Centers in the U.S [Meeting Abstract]
INTRODUCTION: Ustekinumab has been recently approved for the treatment of moderately to severely active ulcerative colitis (UC). The registry trials for ustekinumab in UC demonstrated efficacy and safety, but data on the effectiveness and safety in the real world are limited. We describe the effectiveness and safety of ustekinumab in patients with UC from two US tertiary IBD centers.
METHOD(S): Patients with moderately to severely active UC treated with ustekinumab at NYU Langone Medical Center (New York, NY) and University of Chicago Medical Center (Chicago, IL) between January 2016 and March 2020 were retrospectively included. The primary outcome was clinical remission at 3 and 12 months, defined as a partial Mayo score of 2, with a combined rectal bleeding and stool frequency subscore of #1.
RESULT(S): Sixty-six UC patients were included (Table 1). 61% of patients had extensive colitis and overall mean total Mayo score was 6.5 +/- 2.4. 92% of patients had prior exposure to biologics or tofacitinib. 43% and 45% of patients achieved clinical remission by 3 and 12 months, respectively (Figure 1). Anti-TNF non-response and endoscopic Mayo score of 3 were negative predictors of clinical remission at 3 months (Table 2). At 1 year, 50% of patients achieved endoscopic remission and 33% achieved mucosal and histo-endoscopic healing. The achievement of histo-endoscopic healing was significantly associated with lower partial Mayo score (0.5 +/- 0.6 vs. 3.5 +/- 1.7; P < 0.01) and lower stool frequency (0.3 +/- 0.5 vs. 1.4 +/- 0.7; P = 0.02). Serious adverse events occurred in 4 (6%) patients (3 UC exacerbations, 1 vasculitis).
CONCLUSION(S): In this cohort of mostly biologic-refractory UC patients, treatment with usteki-numab achieved remission in nearly half of them at 12 months, and was associated with an overall favorable safety profile. These results are modestly better than the pivotal trials