Pharmacologic Anticoagulation Is Associated With a Lower Risk of Recurrent Venous Thromboembolic Events During Janus Kinase Inhibitor Use for Patients With a Prior Thrombosis.

BACKGROUND: Janus kinase (JAK) inhibitors tofacitinib and upadacitinib are effective therapies for inflammatory bowel disease and rheumatologic disorders but currently possess a warning for increased venous thromboembolism (VTE) risk. Some patients with a history of VTE may benefit from a JAK inhibitor, but the risk of recurrent VTE with JAK inhibitor use is unclear. Our goal was to observe rates of new VTE events after starting JAK inhibitor therapy in patients with a prior VTE, and observe whether concurrent anticoagulation (AC) reduces this risk. METHODS: We conducted a review of adults prescribed tofacitinib or upadacitinib between January 1, 2000, and June 30, 2023, with a prior history of VTE. Patient charts were reviewed for demographic data, disease type, and VTE date(s), and to verify duration of JAK inhibitor use along with any concurrent AC. VTEs following JAK inhibitor initiation were identified by International Classification of Diseases-Tenth Revision code and verified by physician documentation and imaging. RESULTS: We identified 79 patients with a documented VTE history before initiating JAK inhibitors, 47 of whom began a JAK inhibitor with concurrent AC. Of these, 15 patients discontinued AC while receiving JAK inhibitors. In total, 5 new VTE events were observed during 55.42 patient-years of JAK inhibitor treatment without concurrent AC (9.0 events per 100 patient-years), while no new VTE events occurred during 65.2 patient-years of JAK inhibitor treatment with concurrent AC, demonstrating a lower risk of recurrent VTE (P = .020). CONCLUSIONS: These results suggest that for patients with a prior VTE history there is a high risk for recurrent VTE while receiving JAK inhibitors. Concurrent use of AC with JAK inhibitors appears to be protective against recurrent VTEs in this population.

Patients with a history of venous thromboembolism prior to initiation of a Janus kinase inhibitor (tofacitinib or upadacitinib) had an elevated risk (9%) of recurrent venous thromboembolism on Janus kinase inhibitor, though concurrent anticoagulation may mitigate this risk.

Safety of Immunosuppression in A Prospective Cohort of Inflammatory Bowel Disease Patients with a HIstoRy of CancEr: SAPPHIRE Registry.

BACKGROUND AND AIMS: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies suggest that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared to unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS: Since 2016, patients with IBD and confirmed index cancer prior to enrollment were followed annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within five years were excluded. Primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS: Among 305 patients (47% male, 88% white), median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During median follow-up of 4.8 years, 210 (69%) were exposed to immunosuppressive therapy and 46 (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58/100 person-years versus 4.78/100 PY (relative risk 1.85, 95% CI 0.92-3.73) for immunosuppression exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and non-melanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, aHR, 1.41, 95% CI: 0.69-2.90), or with any major drug class. CONCLUSION: In this interim analysis of patients with IBD and a history of cancer, despite numerically elevated aHRs, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.

Crohn's Disease Mortality and Ambient Air Pollution in New York City.

BACKGROUND: The worldwide increase in Crohn's disease (CD) has accelerated alongside rising urbanization and accompanying decline in air quality. Air pollution affects epithelial cell function, modulates immune responses, and changes the gut microbiome composition. In epidemiologic studies, ambient air pollution has a demonstrated relationship with incident CD and hospitalizations. However, no data exist on the association of CD-related death and air pollution. METHODS: We conducted an ecologic study comparing the number of CD-related deaths of individuals residing in given zip codes, with the level of air pollution from nitric oxide, nitrogen dioxide, sulfur dioxide (SO2), and fine particulate matter. Air pollution was measured by the New York Community Air Survey. We conducted Pearson correlations and a Poisson regression with robust standard errors. Each pollution component was modeled separately. RESULTS: There was a higher risk of CD-related death in zip codes with higher levels of SO2 (incidence rate ratio [IRR], 1.16; 95% confidence interval [CI], 1.06-1.27). Zip codes with higher percentage of Black or Latinx residents were associated with lower CD-related death rates in the SO2 model (IRR, 0.58; 95% CI, 0.35-0.98; and IRR, 0.13; 95% CI, 0.05-0.30, respectively). There was no significant association of either population density or area-based income with the CD-related death rate. CONCLUSIONS: In New York City from 1993 to 2010, CD-related death rates were higher among individuals from neighborhoods with higher levels of SO2 but were not associated with levels of nitric oxide, nitrogen dioxide, and fine particulate matter. These findings raise an important and timely public health issue regarding exposure of CD patients to environmental SO2, warranting further exploration.

Ecologic study comparing the number of Crohn's disease related deaths of individuals residing in given zip codes within New York City, with levels of air pollution from nitric oxide, nitrogen dioxide, sulfur dioxide, and fine particulate matter.

Inflammatory bowel disease and cannabis: key counseling strategies.

PURPOSE OF REVIEW: Cannabis use is becoming more frequent in patients with inflammatory bowel disease (IBD). Because of the increased usage, gastroenterologists need to be cognizant of the benefits and risks associated with cannabis use in the IBD-patient population. RECENT FINDINGS: Recent studies have attempted to determine whether cannabis can improve biomarkers or endoscopic findings of inflammation in patients with IBD, but the results have been inconclusive. However, cannabis has been shown to have an impact on the symptoms and quality of life of individuals with IBD. Despite these benefits, the use of cannabis in IBD is not without risks, including the potential for systemic illness, toxin ingestion and significant drug interactions. SUMMARY: In this review article, we use a case-based approach to discuss the critical clinical data that informs us of the benefits and risks of cannabis use in IBD. The endocannabinoid system plays a crucial role in regulating various physiological functions including the gastrointestinal tract. Studies have investigated the impact of cannabis on various medical conditions, including IBD. Clinicians must be aware of the most recent data to properly educate their patients on the benefits and risks of its use.

Patient adverse events and technical failures with the bravo capsule pH system: insights from the MAUDE database.

BACKGROUND: The BRAVO pH monitor system can benefit patients with ongoing GERD symptoms despite treatment and/or atypical symptoms. We aim to investigate the number and type of complications associated with the BRAVO pH capsule. METHODS: From April 2016 through February 2021, we analyzed post-marketing surveillance data from the FDA Manufacturer and User Facility Device Experience (MAUDE) database. RESULTS: During the study period, approximately 1,651 reports were identified with 2391 cases associated with a device failure, and 254 reporting a patient-related adverse event. Most device complications were due to aspiration n = 153), followed by reported pain (n = 79), injury (unspecified) (n = 63), and additional radiologic imaging (n = 44). Laceration and bleeding accounted for 29 and 19 cases. Furthermore, three patients suffered perforation. Most device failures were due to loss or failure of the Bravo capsule to bond or adhere to the esophageal mucosa as planned (n = 1269), followed by an activation or positioning failure (n = 972), premature detachment of device (n = 284), and failure of the device to record or transmit data (n = 158). CONCLUSIONS: Findings from the MAUDE database highlight the risk of aspiration, hemorrhage/bleeding, perforation, injury, and retention as potential complications of BRAVO capsule placement.

The overall quality of evidence of recommendations surrounding nutrition and diet in inflammatory bowel disease.

BACKGROUND AND AIM: Recently, there has been an increased focus on the role nutrition and diet play in maintaining health in inflammatory bowel disease (IBD). We aimed to assess the overall quality, strength, and transparency of conflicts among guidelines on nutrition/diet in IBD. METHODS: A systematic search was performed on multiple databases from inception until January 1, 2021, to identify guidelines pertaining to nutrition or diet in IBD. All guidelines were reviewed for disclosure of conflicts of interest (COI) and funding, recommendation quality and strength, external document review, patient representation, and plans for update-as per Institute of Medicine (IOM) standards. In addition, recommendations and their quality were compared between guidelines/societies.​ RESULTS: Seventeen distinct societies and a total of 228 recommendations were included. Not all guidelines provided recommendations on key aspects of diet-such as the role of supplements or the appropriate micro/macro nutrition in IBD. Fifty-nine percent of guidelines reported on COI, 24% underwent external review, and 41% included patient representation. 18.4%, 25.9%, and 55.7% of recommendations were based on high-, moderate-, and low-quality evidence, respectively. 10.5%, 24.6%, and 64.9% of recommendations were strong, weak/conditional, and did not provide a strength, respectively. The proportion of high-quality evidence (p = 0.12) and strong recommendations (p = 0.83) did not significantly differ across societies. CONCLUSIONS: Many guidelines do not provide recommendations on key aspects of diet/nutrition in IBD. As over 50% of recommendations are based on low-quality evidence, further studies on nutrition/diet in IBD are warranted to improve the overall quality of evidence.

Cannabis Use and Its Association With Thirty- and Ninety-Day Hospital Readmissions for Patients Admitted for an Inflammatory Bowel Disease Exacerbation.

Background: Though viewed as a potentially safer palliative alternative to opioids, studies of cannabis use for inflammatory bowel disease (IBD) are limited. The impact of opioids on hospital readmissions for IBD has been extensively examined, but cannabis has not been similarly studied. Our goal was to examine the relationship between cannabis use and the risk of 30- and 90-day hospital readmissions. Methods: We conducted a review of all adults admitted for an IBD exacerbation from January 1, 2016 to March 1, 2020 within the Northwell Health Care system. Patients with an IBD exacerbation were identified by primary or secondary ICD10 code (K50.xx or K51.xx) and administration of intravenous (IV) solumedrol and/or biologic therapy. Admission documents were reviewed for the terms "marijuana", "cannabis", "pot" and "CBD". Results: A total of 1,021 patient admissions met inclusion criteria, of whom 484 (47.40%) had Crohn's disease (CD) and 542 (53.09%) were female. Pre-admission cannabis use was reported by 74 (7.25%) patients. Factors found to be associated with cannabis use included younger age, male gender, African American/Black race, current tobacco and former alcohol use, anxiety, and depression. Cannabis use was found to be associated with 30-day readmission among patients with ulcerative colitis (UC), but not among patients with CD, after respectively adjusting each final model by other factors (odds ratio (OR): 2.48, 95% confidence interval (CI): 1.06 - 5.79 and OR: 0.59, 95% CI: 0.22 - 1.62, respectively). Cannabis use was not found to be associated with 90-day readmission on univariable analysis (OR: 1.11, 95% CI: 0.65 - 1.87) nor in the final multivariable model after adjusting for other factors (OR: 1.19, 95% CI: 0.68 - 2.05). Conclusion: Pre-admission cannabis use was found to be associated with 30-day readmission among patients with UC, but not with 30-day readmission for patients with CD nor with 90-day readmission, following an IBD exacerbation.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

A Literature Review of Ozanimod Therapy in Inflammatory Bowel Disease: From Concept to Practical Application.

Inflammatory bowel disease (IBD), namely Ulcerative Colitis (UC) and Crohn's Disease (CD), is believed to be due to a dysregulation of the innate immune response. The complexity of the immune cascade offers both a challenge and an opportunity to researchers seeking out new treatments for IBD, as various points along the inflammatory pathways can be targeted for interruption. Sphinogosine-1-phosphate (S1P) is a phospholipid molecule with wide ranging biological effects caused by binding five known S1P receptor subtypes. Ozanimod is a small molecule drug that selectively targets S1P receptors 1 and 5 which play a crucial role in lymphocyte trafficking. In clinical trials for both UC and CD, it has been shown to induce a reversible lymphopenia which correlates with response to therapy. Reported adverse events include infection, anemia, and elevated liver enzymes. Rare instances of bradycardia, heart block, and macular edema were also reported. As a newly available therapy approved for UC patients, we aim to summarize ozanimod's novel mechanism of action, pre-clinical and clinical trial results, and to give context to this newly available drug that gastroenterologists may utilize in their treatment algorithm.

Endoscopic Disease Activity and Biologic Therapy Are Independent Predictors of Suboptimal Bowel Preparation in Patients with Inflammatory Bowel Disease Undergoing Colonoscopy.

BACKGROUND AND AIMS: Optimal bowel preparation (BP) is critical for endoscopic assessment of inflammation and dysplasia in patients with inflammatory bowel disease (IBD). Comorbidities and patient-related factors have been associated with suboptimal BP (SOBP) in the general population. We sought to identify disease-specific characteristics that may impact the quality of BP in patients with IBD. METHODS: We conducted a retrospective analysis of adult IBD patients who underwent outpatient colonoscopies between January 2014 and September 2020 at a large academic medical center. Quality of BP was documented using the Boston Bowel Preparation Scale (BBPS) or the Aronchick scale and dichotomized into "suboptimal" (BBPS 0-5 or Aronchick "fair," "poor," unsatisfactory") and "optimal" (BBPS 6-9 or Aronchick "excellent," "good"). IBD-specific and other factors associated with SOBP were evaluated using logistic regression analyses. RESULTS: Among a total of 395 IBD patients [54% males, mean age 40 years, 63% with Crohn's disease (CD), 35% with ulcerative colitis (UC)], 24.8% had SOBP. On multivariable analysis, moderate-to-severe endoscopic disease vs mild or inactive disease was associated with a higher odds of SOBP [adjusted OR 2.7(95% CI 1.52-4.94)], whereas baseline biologic use was associated with a lower odds of SOBP [aOR 0.24(0.09-0.65)] among the overall IBD cohort. Additionally, age > 65 years [aOR 2.99(1.19-7.54)] and single-dose vs split-dose BP [aOR 2.37(1.43-3.95)] were predictors of SOBP. In the subgroup analysis by IBD type, moderate-to-severe endoscopic disease predicted SOBP among both CD and UC cohorts. CONCLUSION: Endoscopic disease activity was predictive of SOBP, and biologic therapy was protective against SOBP among IBD patients.

Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis.

BACKGROUND & AIMS: We aimed to compare safety and effectiveness of vedolizumab to tumor necrosis factor (TNF)-antagonist therapy in ulcerative colitis in routine practice. METHODS: A multicenter, retrospective, observational cohort study (May 2014 to December 2017) of ulcerative colitis patients treated with vedolizumab or TNF-antagonist therapy. Propensity score weighted comparisons for development of serious adverse events and achievement of clinical remission, steroid-free clinical remission, and steroid-free deep remission. A priori determined subgroup comparisons in TNF-antagonist-naïve and -exposed patients, and for vedolizumab against infliximab and subcutaneous TNF-antagonists separately. RESULTS: A total of 722 (454 vedolizumab, 268 TNF antagonist) patients were included. Vedolizumab-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists. Results were consistent across subgroup analyses in TNF-antagonist-naïve and -exposed patients, and for vedolizumab vs infliximab and vs subcutaneous TNF-antagonist agents separately. Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between vedolizumab-treated and TNF-antagonist-treated patients. However, in TNF-antagonist-naïve patients, vedolizumab was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). CONCLUSIONS: Treatment of ulcerative colitis with vedolizumab is associated with higher rates of remission than treatment with TNF-antagonist therapy in routine practice, and lower rates of serious adverse events in TNF-antagonist-naïve patients.

Endo-hepatology: An emerging field.

Gastroenterologists have long been spearheading the care of patients with various forms of liver disease. The diagnosis and management of liver disease has traditionally been a combination of clinical, laboratory, and imaging findings coupled with percutaneous and intravascular procedures with endoscopy largely limited to screening for and therapy of esophageal and gastric varices. As the applications of diagnostic and therapeutic endoscopic ultrasound (EUS) have evolved, it has found a particular niche within hepatology now coined endo-hepatology. Here we discuss several EUS-guided procedures such as liver biopsy, shear wave elastography, direct portal pressure measurement, paracentesis, as well as EUS-guided therapies for variceal hemorrhage.

Safety of biologics in inflammatory bowel disease patients with COVID-19.

BACKGROUND: Patients with Inflammatory bowel disease (IBD) remain highly concerned that either their disease or medications-namely, biologics-may increase the risk of severe coronavirus-2019 (COVID-19). We aimed to assess the safety of biologics in Inflammatory bowel disease (IBD) patients with COVID-19. METHODS: We systematically reviewed multiple databases to find relevant articles reporting the effect of biologics on "severe" COVID-19 in IBD patients. Those in the form of case series (> 10 patients), case-control, and cohort studies were included. Severe COVID-19 was defined as intensive care unit (ICU) admission, mechanical ventilation, and/or mortality. Pooled analysis with multivariate regression was performed. RESULTS: A total of 12 studies with 2681 patients were included. The proportion of females was (48.3%, 95% confidence interval (CI) 47.0-49.5%). The proportion of UC patients was (44.8%, 95% CI 41.0-48.5%). Overall, in IBD patients, the need for mechanical ventilation, intensive care unit (ICU) admission, and mortality was 5.1%, 6.1%, and 4.5%, respectively. Use of biologics did not show a moderating effect on mechanical ventilation (p = 0.68), ICU admission (p = 0.27), or mortality (p = 0.20). CONCLUSIONS: Our findings advocate for the continued biologic therapy in IBD patients during the COVID-19 pandemic. Nevertheless, the incidence, severity, and outcomes related to COVID-19 in IBD patients' needs to be reassessed as data continues to emerge.

Inflammatory Bowel Disease and Cannabis: A Practical Approach for Clinicians.

Although still not approved at the federal level for medical or adult recreational use, cannabis has been approved in the United States (USA) by individual states for both of these purposes. A total of 15 states now regulate cannabis for adult use and 36 states for medical use. In more recent years, cannabis has gained popularity for the treatment of chronic conditions, inflammatory bowel disease (IBD) being one of them. However, the exact role of cannabis in the treatment of IBD remains uncertain. While cannabis may help in some instances with symptom management, it has not been proven to help with inflammation or to fundamentally correct underlying disease processes. Additionally, along with the perceived symptom benefits of cannabis come concerning issues like dosing inconsistencies, dependence, and cannabinoid hyperemesis syndrome. In this review article, we explore the nuanced relationship between cannabis and the treatment of IBD by summarizing the current research. We also use clinical vignettes to discuss the more practical considerations surrounding its use.

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn's Disease.

BACKGROUND & AIMS: This study compared the effectiveness of the Specific Carbohydrate Diet (SCD) to the Mediterranean diet (MD) as treatment for Crohn's disease (CD) with mild to moderate symptoms. METHODS: Adult patients with CD and with mild-to-moderate symptoms were randomly assigned 1:1 to consume the MD or SCD for 12 weeks. For the first 6 weeks, participants received prepared meals and snacks according to their assigned diet. After 6 weeks, participants were instructed to follow the diet independently. The primary outcome was symptomatic remission at week 6. Key secondary outcomes at week 6 included fecal calprotectin (FC) response (FC <250 µg/g and reduction by >50% among those with baseline FC >250 µg/g) and C-reactive protein (CRP) response (high-sensitivity CRP <5 mg/L and >50% reduction from baseline among those with high-sensitivity CRP >5 mg/L). RESULTS: The study randomized 194 patients, and 191 were included in the efficacy analyses. The percentage of participants who achieved symptomatic remission at week 6 was not superior with the SCD (SCD, 46.5%; MD, 43.5%; P = .77). FC response was achieved in 8 of 23 participants (34.8%) with the SCD and in 4 of 13 participants (30.8%) with the MD (P = .83). CRP response was achieved in 2 of 37 participants (5.4%) with the SCD and in 1 of 28 participants (3.6%) with the MD (P = .68). CONCLUSIONS: The SCD was not superior to the MD to achieve symptomatic remission, FC response, and CRP response. CRP response was uncommon. Given these results, the greater ease of following the MD and other health benefits associated with the MD, the MD may be preferred to the SCD for most patients with CD with mild to moderate symptoms. ClinicalTrials.gov Identifier: NCT03058679.