Hashash, Jana G

Abstract Background An increasing incidence of pediatric-onset inflammatory bowel disease (PIBD) has been reported in many countries. However, the global burden and distribution of this disease remain less understood. We aimed to examine the global epidemiology and trends of PIBD from 1990 to 2019. Methods Data from the 2019 Global Burden of Disease Study, covering 204 countries, were analyzed. We assessed key measures like incidence, prevalence, mortality, and disability-adjusted life years (DALYs) using linear regression to calculate annual percentage changes and assess trends. Results Between 1990 and 2019, the PIBD incidence rate increased and the DALY rate and mortality rate declined. The incidence rate was notably elevated in the high Socio-demographic Index (SDI) quintile, reaching 6.3 per 100 000 person-years, corresponding to 13 914 new cases in 2019. Incidence and prevalence of PIBD positively correlated with the SDI, while higher death and DALY burdens were observed in lower-SDI countries. In 2019, the top 5 countries with the highest PIBD incidence rates were Canada (19.9 per 100 000 population), Denmark (12.4 per 100 000 population), Hungary (8.5 per 100 000 population), Austria (8.1 per 100 000 population), and the United States (7.4 per 100 000 population). Several countries experienced significant increases in incidence rates from 1990 to 2019, led by Taiwan (annual percent change 4.2%), followed by China (2.8%), Japan (2.1%), Australia (1.8%), and Hungary (1.6%). Discussion PIBD incidence has significantly increased since 1990. High-SDI countries face higher incidence, while lower-SDI countries experience higher mortality and DALY burdens. The study underscores the need for ongoing monitoring and research to address this emerging public health issue.

Abstract Background Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown sustained and clinically significant weight loss in the general population. There are limited data on outcomes of its use in patients with inflammatory bowel disease (IBD). Methods A retrospective cohort study was conducted between June 4, 2021, and December 11, 2023, using TriNetX, a U.S. multi-institutional database in patients with obesity who had IBD compared with patients without IBD. The primary aim was to assess the mean total body weight (TBW) change between 6 and 15 months from initiation of semaglutide compared with baseline between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographics, comorbid conditions, smoking status, and mean body mass index. A 2-sample t test was performed to assess mean TBW change from baseline, with a P value <.05 considered to be statistically significant. We also compared the risk of IBD-specific outcomes with and without semaglutide use in patients with IBD. Results Out of 47 424 patients with IBD and obesity, 150 (0.3%) patients were prescribed semaglutide (mean age 47.4 ± 12.2 years; mean TBW 237 ± 54.8 pounds; mean body mass index 36.9 ± 6.5 kg/m2; 66% Crohn’s disease). There was no difference in mean TBW change after initiation of semaglutide in the IBD and non-IBD cohorts (−16 ± 13.4 pounds vs −18 ± 12.7 pounds; P = .24). There was no difference in mean TBW change between 6 and 12 months (−16 ± 13 pounds vs −15 ± 11.2 pounds; P = .24) and 12 and 15 months (−20 ± 13.2 pounds vs −21 ± 15.3 pounds; P = .49) between the 2 cohorts. There was no difference in the risk of oral or intravenous steroid use and any-cause hospitalization in the semaglutide group compared with the group without semaglutide use in patients with IBD. Conclusion Semaglutide use is effective in patients with IBD and obesity similar to patients without IBD, with >5% mean weight loss. There was no increased risk of IBD-specific adverse events with semaglutide use.

Abstract Introduction Crohn’s disease (CD) with short bowel syndrome (SBS) can present as chronic intestinal failure (CIF) often requiring nutritional support. Teduglutide is a treatment option for these patients. We investigated clinical outcomes of CD-CIF patients with SBS treated with teduglutide. Methods Adults with CD-CIF and SBS who received teduglutide were identified at a tertiary care academic center between 2012 and 2023. Data was collected retrospectively. Primary outcome measured was reduction in parenteral support (PS) by ≥20% volume, with PS defined as utilization of parenteral nutrition (PN) or intravenous fluids (IVF). Several secondary outcomes included immunosuppressive medication changes, subjective symptom improvement, and stool output. Results We identified 32 patients with CD-CIF and SBS receiving teduglutide. Comparing clinical outcomes before and after teduglutide, 26 of 32 patients achieved the primary outcome of ≥20% PS reduction. A decrease was seen in patients requiring PN + IVF, with corresponding increases in patients requiring PN only and IVF only. Among all 3 groups, a total of 23 patients received PN prior to teduglutide, which decreased to 14 following teduglutide. Weekly PN volume reduced from 7.00 to 3.55 L and weekly frequency decreased from 7.00 to 3.00 instances (P < .01). Reductions in weekly volume and frequency were observed among all patients receiving IVF support (25 vs 15). Secondary outcomes showed improvement in patient reported subjective symptoms (84.4%), stool output (90.6%), patients meeting criteria for diarrhea/high ostomy output (27 vs 14), and use of unique antidiarrheal medications (3.0 vs 2.0). Conclusions This retrospective case series demonstrated improved clinical outcomes in patients with CD-CIF and SBS treated with teduglutide resulting in decreased PS requirements, antidiarrheal medications requirement, and stool output without significant effects on immunosuppressive therapy.

Abstract Background Approximately 15%–20% of patients with ulcerative colitis (UC) will require surgery during their lifetime. Ileal pouch–anal anastomosis (IPAA) is the preferred surgical option, which typically requires access to a specialist experienced in surgery for inflammatory bowel diseases (IBD). Methods The aims of this study are the assessment of the comparative use of IPAA for UC among different racial/ethnic groups and observe trends over the past decade in the United States as well as the comparative assessment of their respective postoperative outcomes. This was an observational retrospective study using the National Inpatient Sample (NIS) 2009–2018 dataset. All patients with ICD-9/10CM codes for UC were included. The primary outcome was comparative trends in IPAA construction across races/ethnicities in the past decade, which was compared to White patients as reference. Multivariate regression analyses were used to adjust for age, gender, Charlson comorbidity index, income in patient zip code, insurance status, hospital region, location, size, and teaching status. Results The number of patients discharged from US hospitals with an associated diagnosis of UC increased between 2009 and 2018, but the number of patients undergoing an IPAA decreased during that time period. Of 1 153 363 admissions related to UC, 60 688 required surgery for UC, of whom 16 601 underwent IPAA in the study period. Of all the patients undergoing surgery for UC, 2862 (4.7%) were Black, while 44 351 were White. This analysis indicated that Black patients were less likely to undergo IPAA both in 2009 and in 2018 compared to Whites. Hispanic patients were significantly less likely to receive IPAA in 2009 but were no longer less likely to receive IPAA in 2018 when compared to Whites. Conclusions The use of IPAA among Black patients requiring surgery for UC remains less common than amongst their White counterparts. Further research is needed to determine if racial disparity is a factor in decreased access to specialized care.

Abstract Background Tixagevimab and cilgavimab (Evusheld) are 2 fully human monoclonal antibodies that received emergency-use authorization on December 21, 2021, for pre-exposure prophylaxis of coronavirus disease 2019 (COVID-19) in patients who are moderate–severely immunocompromised. The real-world efficacy of Evusheld in patients with inflammatory bowel disease (IBD) is not known. Methods We conducted a retrospective cohort study using TriNetX, a multi-institutional database in patients with IBD who received Evusheld compared to patients with IBD who did not receive Evusheld (12.1.2021–10.28.2022). The primary outcome was to assess the risk of COVID-19 within 6 months. One-to-one propensity score matching (PSM) was performed for demographic parameters, comorbid conditions, IBD medications, and history of COVID-19. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). Results Four hundred and eight patients (0.19%) with IBD received Evusheld (mean age 58.6 ± 15.4 years old, female 47.7%) during the study period. After PSM, there was no difference in the risk (aOR 0.88, 95% CI, 0.33–2.35) of COVID-19 in the Evusheld cohort compared to the IBD control cohort. No patients required ICU care or intubation/respiratory support or were deceased in the Evusheld cohort. Conclusions Our study did not show that Evusheld decreases the risk of COVID-19 in patients with IBD. Prevention of moderate–severe COVID-19 in these patients should focus on vaccination strategies and early COVID-19 therapies.

Abstract Background There is evidence that SARS-CoV2 infection can increase the risk of herpes zoster (HZ) in the general population. However, the risk in patients with inflammatory bowel disease (IBD) is not known. Methods The TriNetX database was utilized to conduct a retrospective cohort study in patients with IBD after SARS-CoV2 infection and patients without a SARS-CoV2 infection (IBD control cohort). The primary outcome was to evaluate the risk of HZ between the 2 cohorts. One-to-one (1:1) propensity score matching was performed for demographic parameters, HZ risk factors and IBD medications between the 2 cohorts. Adjusted odds ratio (aOR) with 95% confidence interval (CI) were calculated. Results After propensity score matching, patients with IBD with a SARS-CoV2 infection were at an increased risk for HZ (aOR, 2.16; 95% CI, 1.53-3.04) compared with IBD control cohort in the pre-COVID-19 vaccine era. There was no difference in the risk (aOR, 0.87; 95% CI, 0.44-1.75) of a composite outcome of HZ complications (hospitalization, post-herpetic neuralgia, and neurologic complications) between the 2 cohorts. The IBD SARS-CoV2 cohort was also at an increased risk for HZ (aOR, 3.04; 95% CI, 1.48-6.24) compared with IBD control cohort in the postvaccine era. However, the risk of HZ in the postvaccine era was decreased (aOR, 0.45; 95% CI, 0.27-0.76) compared with IBD SARS-CoV2 cohort in the prevaccine era. Conclusions Our study showed that SARS-CoV2 infection is associated with an increased risk of HZ in patients with IBD.

Lay Summary It is unknown if immune checkpoint inhibitor therapy increases risk of pouch-related complications in patients with inflammatory bowel disease after ileal-pouch anal anastomosis. In our study, pembrolizumab therapy was not associated with significant gastrointestinal immune-related adverse events or pouch-related complications.

Abstract Background Despite the growing therapeutic armamentarium, at least half of the patients with Crohn’s disease will require surgery during their lifetime. Current evidence for the prevention and treatment of postoperative Crohn’s disease supports the use of anti-tumor necrosis factor agents with limited data about the use of the newer biologics, vedolizumab and ustekinumab. Methods We performed a systematic review of available data to determine the efficacy of the newer biologics in the management of postoperative Crohn’s disease. We included noncomparative and comparative studies. The main outcomes of interest were clinical and endoscopic postoperative recurrence rates. Results The search strategy identified 1231 citations, with 32 eligible for review. Several studies showed that the postoperative Crohn’s disease recurrence rates with the use of the newer biologics were comparable to previously published results with the use of anti-tumor necrosis factor agents, while other studies failed to show their efficacy. It is important to note that the studies were heterogeneous and included a relatively small sample size, making it difficult to draw a definite conclusion about the efficacy of the newer biologics in the management of postoperative Crohn’s disease. Conclusion The newer biologics do play a role in the management of postoperative Crohn’s disease. After our review, we proposed an updated algorithm on the role of newer biologics in the approach to patients with postoperative Crohn’s disease. Yet, until we have better-designed studies, their definite positioning remains to be determined.

Abstract Background Fecal microbiota transplantation (FMT) has been investigated as a treatment option for patients with inflammatory bowel disease with controversial results. We sought to perform a systematic review and meta-analysis to evaluate the benefit of FMT in patients with ulcerative colitis. Methods Double-blind randomized controlled trials (RCTs) including adult patients with active ulcerative colitis who received either FMT or placebo were eligible for inclusion. Outcomes of interest included the rate of combined clinical and endoscopic remission, endoscopic remission or response, clinical remission or response, and specific adverse events. The results were pooled together using Reviewer Manager 5.4 software. Publication bias was assessed using the Egger’s test. Results Six RCTs involving 324 patients were included. Our findings demonstrate that compared with placebo, FMT has significant benefit in inducing combined clinical and endoscopic remission (odds ratio, 4.11; 95% confidence interval, 2.19-7.72; P < .0001). Subgroup analyses of influencing factors showed no differences between pooled or single stool donors (P = .71), fresh or frozen FMT (P = .35), and different routes or frequencies of delivery (P = .80 and .48, respectively). Pre-FMT antibiotics, bowel lavage, concomitant biologic therapy, and topical rectal therapy did not affect combined remission rates (P values of .47, .38, .28, and .40, respectively). Clinical remission or response and endoscopic remission or response were significantly higher in patients who received FMT compared with placebo (P < .05) without any differences in serious or specific adverse events. Conclusions FMT demonstrated a clinical and endoscopic benefit in the short-term treatment of active ulcerative colitis, with a comparable safety profile to placebo. Future RCTs are required to standardize study protocols and examine data on maintenance therapy.