Utility of a Third Heplisav-B Dose in Patients with Inflammatory Bowel Disease without Immunity Following Two-Dose Heplisav-B Vaccination.

OBJECTIVES: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the two-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite two-dose vaccination. METHODS: Adults with IBD who had received two-dose Heplisav-B vaccination between 2018-2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) >10 IU/L measured at >4 weeks following vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data was compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted following two-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1000 IU/L) despite a median inter-vaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did versus did not seroconvert following third dose vaccination. CONCLUSION: In patients with IBD lacking HBV immunity despite two-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary two-dose vaccination.

In Patients With Inflammatory Bowel Disease, Racial Disparities Exist in Burden of Vaccine-preventable Disease Hospitalizations and Outcomes.

OBJECTIVE: Patients with inflammatory bowel disease (IBD) are at increased risk of vaccine-preventable diseases (VPDs). Despite the increasing prevalence of IBD in non-white populations, little is known regarding racial disparities in VPD burden. METHODS: Retrospectively analyzing the 2016 to 2020 National Inpatient Sample, we identified adults with IBD hospitalized for a principal diagnosis of VPD. The primary outcome investigated was hospitalization for VPD stratified by patient-reported race. Secondary outcomes were in-hospital morbidity, mortality, length of stay, and health care utilization. Multivariable regression analysis was performed to adjust for patient and hospital characteristics. RESULTS: The search identified 554,114 hospitalizations for VPD, including 4170 hospitalizations in patients with IBD. Patients with IBD had significantly greater odds of hospitalization from herpes zoster virus (adjusted odds ratio [aOR]: 1.73) and varicella zoster virus (aOR: 2.31). Comparing white and non-white patients with IBD, significant racial disparities were noted. Non-white patients were at greater odds of hospitalization from influenza (aOR: 1.74), herpes zoster virus (aOR: 1.77), and varicella zoster virus (aOR: 1.62). In-hospital morbidity was greater in non-white patients, including greater odds of requiring intensive care unit stay (aOR: 1.18). Morbidity was elevated in African Americans, with greater odds of acute kidney injury (aOR: 1.25), venous thromboembolism (aOR: 1.17), respiratory failure (aOR: 1.16), and intensive care unit stay (aOR: 1.18). No differences were found in mortality, length of stay, and health care utilization. CONCLUSIONS: Significant racial disparities in VPD hospitalization and in-hospital morbidity were found among adults with IBD in the United States. With the increasing prevalence of IBD in non-white populations, targeted efforts are needed to improve health equity.

Patients With Inflammatory Bowel Disease Are at Increased Risk of Hospitalization Due to Respiratory Syncytial Virus.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk of developing respiratory infections. Respiratory syncytial virus (RSV) is a common respiratory virus with adverse outcomes in older adults. This study aimed to determine whether patients with IBD are at increased risk of a serious infection due to RSV. METHODS: We conducted a retrospective study using the multi-institutional research network TriNetX to assess the risk of hospitalization in a cohort of patients with IBD compared with that in a non-IBD control cohort with RSV infection from January 1, 2007, to February 27, 2023. One-to-one (1:1) propensity score matching was performed for demographic variables and RSV risk factors between the 2 cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULTS: There were 794 patients in the IBD-RSV cohort and 93,074 patients in the non-IBD-RSV cohort. The mean age of the IBD-RSV cohort was 55.6 ± 20 years, 59% were female, 80% were White, and 56.9% had Crohn's disease. The IBD-RSV cohort was at an increased risk of hospitalization (aOR 1.30, 95% CI 1.06-1.59). There was no difference in the risk (aOR 0.83, 95% CI 0.58-1.19) of a composite outcome of hospitalization-related complications between the 2 cohorts. Recent systemic corticosteroid use (<3 months) was associated with an increased risk of hospitalization (aOR 1.86, 95% CI 1.30-2.59) in the IBD-RSV cohort. DISCUSSION: We found that adult patients with IBD and RSV infection are at an increased risk of hospitalization and may benefit from the new RSV vaccine recommended for adults aged 60 years and older.

A Practical Update on COVID-19 and Inflammatory Bowel Disease: COVID-19 Disease Risk and Vaccine Safety and Efficacy.

The COVID-19 pandemic introduced significant uncertainty regarding the care of patients with inflammatory bowel disease (IBD). Substantial research efforts have made progress in answering many of the questions that arose, but the constantly shifting paradigm of COVID-19-related research and recommendations has made it challenging for IBD clinicians to remain up-to-date. The goal of this article is to provide a concise and practical summary of the literature evaluating COVID-19 disease risk in addition to COVID-19 vaccine safety, immunogenicity, real-world effectiveness, and uptake among patients with IBD.

Higher and Sustained Cell-Mediated Immune Responses After 3 Doses of mRNA COVID-19 Vaccine in Patients With Inflammatory Bowel Disease on Anti-Tumor Necrosis Factor Therapy.

INTRODUCTION: Studies suggest that the generation of durable T-cell immunity following coronavirus disease 2019 (COVID-19) vaccination protects against severe disease. The aim of this study was to measure cell-mediated immune response (CMIR) 1-2 months and 6 months after a third dose of a COVID-19 mRNA vaccine. METHODS: This prospective study (HumoRal and CellULar initial and Sustained immunogenicity in patients with inflammatory bowel disease [IBD]) evaluated CMIR at 28-65 days (t 1 ) after dose 2, 28-65 days (t 2 ) (n = 183) and 6 months (±45 days) (t 3 ) (n = 167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood sample available 28-65 days (t 4 ) (n = 55) after a fourth dose. Primary outcomes were CMIR at (t 2 ) and (t 3 ). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t 4 ). RESULTS: All patients had measurable CMIR at all time points. CMIR increased at t 2 compared with that at t 1 (median 1,467 responding cells per million (interquartile range [IQR] 410-5,971) vs 313 (94-960) P < 0.001). There was no significant waning in t 2 vs t 3 or significant boosting at t 4 . Those on anti-tumor necrosis factor monotherapy had a higher CMIR compared with those not on this therapy at t 2 (4,132 [IQR 1,136-8,795] vs 869 [IQR 343-3,221] P < 0.001) and t 3 (2,843 [IQR 596-6,459] vs 654 [IQR 143-2,067] P < 0.001). In univariable analysis, anti-tumor necrosis factor monotherapy was associated with a higher CMIR at t 2 ( P < 0.001) and t 3 ( P < 0.001) and confirmed in a multivariable model ( P < 0.001). DISCUSSION: A third dose of a COVID-19 vaccine boosts CMIR, and the response is sustained in patients with IBD.

Recombinant Zoster Vaccine (RZV) is Effective in Patients with Inflammatory Bowel Disease: A US Propensity Matched Cohort Study.

BACKGROUND: Recombinant zoster vaccine (RZV) reduces the short-term risk of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD). However, there is lack of data regarding the long-term effectiveness in this population. METHODS: A retrospective cohort study was conducted in adults ≥50 years old using TriNetX database between patients with IBD who received 2 doses of RZV (IBD-RZV cohort) and patients who did not receive RZV (IBD control cohort). The primary outcome was risk of incident HZ. One-to-one propensity score matching was performed for demographic parameters, co-morbid conditions and IBD medications. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence intervals (CI). RESULT: The IBD-RZV cohort (n=5489; mean age 63.2 ±9.1 years old and 57.2% females) was identified with a mean follow-up of 900.9 days. IBD-RZV cohort had a lower risk of HZ (aOR 0.44, 95% CI 0.32-0.62) compared to IBD control cohort. The risk of HZ was lower in patients aged 50-65 years old (aOR 0.41, 95% CI 0.25-0.68) and patients > 65 years old (aOR 0.64, 95% CI 0.42-0.96). There was a lower risk of HZ in patients with ulcerative colitis (aOR 0.41, 95% CI 0.27-0.63) and Crohn's disease (aOR 0.44, 95% CI 0.26-0.74) in the IBD-RZV cohort compared to IBD control cohort. CONCLUSION: RZV is associated with a lower long-term risk of HZ in patients ≥50 years old with IBD. Given the widespread availability and safety of RZV, more effective vaccination strategies are needed to improve RZV utilization in this high-risk population.

Racial, Ethnic, and Geographic Disparities in Immunization Rates Among Patients With Inflammatory Bowel Disease.

Background and Aims: Racial and ethnic disparities exist in the treatment of IBD. These disparities exist in adult vaccine uptake among the general population and may extend to patients with IBD. The primary aim of this study was to determine whether racial, ethnic, or geographic disparities existed in influenza vaccine uptake among patients with IBD. Methods: We performed a multicenter, retrospective cohort study evaluating adult vaccine uptake among patients with IBD seen at two tertiary referral centers between September 2019 and February 2020. The primary outcome was to determine if racial/ethnic and geographic disparities existed in influenza vaccine uptake for the two prior seasons. Our secondary outcomes were to determine if disparities existed for pneumococcal, zoster, or hepatitis B vaccines. Results: Among the 2453 patients who met the inclusion criteria, most identified as non-Hispanic White (89.9%), were on immunosuppressive therapy (74.5%), and received the influenza vaccine in both seasons (56.0%). Older age (prevalence ratio (PR) 0.98; 95% confidence interval (95%CI) 0.98-0.99; P < .001) and non-Hispanic White patients (PR 0.76, 95%CI 0.59-0.98, P < 0.03) were significantly more likely to be immunized. Black patients (PR 1.37; 95%CI 1.18-1.59; P < .001) and those living in underserved geographic areas (PR 1.35; 95%CI 1.17-1.56; P < 0.001) were less likely to be immunized. Racial/ethnic and geographic disparities were identified for pneumococcal, zoster, and hepatitis B vaccine uptake. Conclusions: Racial and ethnic vaccination uptake disparities exist among patients with IBD; patients from medically underserved areas are also vulnerable to these disparities Studies identifying patient, provider, and system-level opportunities to address these disparities are needed.

Increased Risk of Herpes Zoster in Adult Patients with Inflammatory Bowel Disease After SARS-CoV2 Infection: A Propensity-Matched Cohort Study.

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.

Prevalence of Immunomodulator Use as Combination Therapy With Vedolizumab or Ustekinumab in Inflammatory Bowel Disease.

INTRODUCTION: The benefit of adding an immunomodulator to vedolizumab and ustekinumab remains unclear and may compromise the safety of these biologics. We evaluated the prevalence and predictors of immunomodulator use with vedolizumab or ustekinumab in patients with inflammatory bowel disease in a large longitudinal cohort. METHODS: Clinical information was ascertained from electronic medical records of patients enrolled in TARGET-IBD, a prospective longitudinal observational cohort of patients with inflammatory bowel disease (IBD) at 34 sites. The prevalence of immunomodulator use with vedolizumab, ustekinumab, and antitumor necrosis factor therapies and predictors of immunomodulator use with vedolizumab and ustekinumab were estimated. Rates of combination therapy were additionally stratified by time from drug approval. RESULTS: Four thousand thirty-nine adults with IBD were identified, of whom 18.8% were treated with vedolizumab and 13.0% were treated with ustekinumab. Combination therapy with vedolizumab and ustekinumab exceeded 30% (30.7% and 36.2%, respectively) and was more likely in those with perianal disease or previous biologic exposure. Age and presence of extraintestinal manifestations did not consistently predict the use of an immunomodulator. Combination therapy decreased in the years after drug approval. DISCUSSION: Combination therapy with vedolizumab or ustekinumab was common and was associated with perianal disease and greater exposure to other biologics, although the practice is decreasing with time. Further data are needed to determine the efficacy and safety of combination therapy in patients initiating vedolizumab or ustekinumab for IBD.

COVID-19 vaccination in adults with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) are not at increased risk of SARS-CoV-2 infection compared to the general population, and most are not at increased risk for severe disease. COVID-19 is nonetheless common, and vaccination is critical. Four safe and efficacious vaccines are now available for the prevention of COVID-19, with most data available for mRNA vaccines. Patients with IBD have a robust humoral response to vaccination with rates of seroconversion exceeding 95% following a two-dose mRNA vaccine series and 99% following a three-dose mRNA series, although those on certain therapies including anti-tumor necrosis factor α agents may have lower antibody concentrations and waning of antibodies over time. Additionally, rates of cell-mediated immune response, even in those patients with IBD who did not have evidence of humoral immunity, are high. Vaccines are safe and have not been associated with flares in disease activity. Gastroenterology providers should take an active role in ensuring patients with IBD are appropriately vaccinated against COVID-19.

Thromboembolic Events in Hospitalized Patients with Inflammatory Bowel Disease.

BACKGROUND: Inflammatory bowel disease (IBD) has been associated with an increased risk of thromboembolic vascular complications. Although studies from the National Inpatient Sample (NIS) examined this association to some extent, sub-stratification for Crohn's disease (CD) and ulcerative colitis (UC) in larger studies is lacking. The aims of this study were to utilize the NIS to determine the prevalence of thromboembolic events in inpatients with IBD compared to in patients without IBD and to explore the inpatient outcomes like morbidity, mortality, and resource utilization in patients with IBD and thromboembolic events as stratified by disease subtype. METHODS: This was a retrospective observational study using the NIS 2016. All patients with ICD10-CM codes for IBD were included. Patients with thromboembolic events were identified using diagnostic ICD codes and stratified into 4 categories: (1) Deep vein thrombosis (DVT), (2) Pulmonary embolism (PE), (3) Portal vein thrombosis (PVT), and (4) Mesenteric ischemia, which were then sub-stratified for CD and UC. The primary outcome was the inpatient prevalence and odds of thromboembolic events in patients with IBD compared to without IBD. Secondary outcomes were inpatient morbidity, mortality, resource utilization, colectomy rates, hospital length of stay (LOS), and total hospital costs and charges compared to patients with IBD and thromboembolic events. RESULTS: A total of 331,950 patients with IBD were identified, of who 12,719 (3.8%) had an associated thromboembolic event. For the primary outcome, after adjusting for confounders, inpatients with IBD had higher adjusted odds of DVT (aOR 1.59, p < 0.001), PE (aOR 1.20, p < 0.001), PVT (aOR 3.18, p < 0.001) and mesenteric ischemia (aOR 2.49, p < 0.001) compared to inpatients without IBD, an observation which was confirmed for both patients with CD and UC. Inpatients with IBD and associated DVT, PE and mesenteric ischemia had higher morbidity, mortality, odds of colectomy, cost, and charges. CONCLUSIONS: Inpatients with IBD have higher odds of associated thromboembolic disorders compared to patients without IBD. Furthermore, inpatients with IBD and thromboembolic events have significantly higher mortality, morbidity, colectomy rates and resource utilization. For these reasons, increased awareness and specialized strategies for the prevention and management of thromboembolic events should be considered in inpatients with IBD.

Cost-effectiveness of an adjuvanted recombinant zoster vaccine in adults with inflammatory bowel disease.

BACKGROUND: Recombinant zoster vaccine (RZV) is recommended for all adults ≥19 years of age who are at increased risk for HZ, including patients with inflammatory bowel disease (IBD). METHODS: A Markov model was constructed to compare the RZV cost-effectiveness with no vaccination in patients with Crohn's Disease (CD) and ulcerative colitis (UC). A simulated cohort of 1 million patients was used for each IBD group at ages 18, 30, 40, and 50. The primary objective of this analysis was to compare RZV cost-effectiveness in patients with CD and UC, comparing vaccination to no vaccination. RESULTS: Overall, vaccination is cost-effective for both CD and UC, with the incremental cost-effectiveness ratio (ICERs) below $100,000/quality-adjusted life years (QALY) for all age cohorts. For patients with CD, 30 years of age and older, and those with UC 40 years and older, vaccination was both more effective and less expensive than the non-vaccinated strategy (CD ≥30: ICERs $6183-$24,878 and UC ≥40: ICERs $9163-$19,655). However, for CD patients under 30 (CD 18: ICER $2098) and UC patients under 40 (UC = 18: ICER $11,609, and UC = 30: $1343), costs were greater for vaccinated patients, but there was an increase in QALY. One-way sensitivity analysis of age indicates that cost break-even occurs at age 21.8 for the CD group and 31.5 for the UC group. In probabilistic sensitivity analysis, 92% of both CD and UC simulations indicated that vaccination was preferred. CONCLUSION: In our model, vaccination with RZV was cost-effective for all adult patients with IBD.

Persistence of Antibodies Six Months after Three COVID-19 mRNA Vaccine Doses in Patients with Inflammatory Bowel Disease.

We evaluated antibody concentrations 6 months after a third coronavirus disease 2019 messenger RNA vaccine dose in patients with inflammatory bowel diseases. Almost all patients had an antibody response, and those with a previous SARS-CoV-2 infection had higher antibody concentrations.