Higher and Sustained Cell-Mediated Immune Responses after Three Doses of mRNA COVID-19 Vaccine In Patients with Inflammatory Bowel Disease on Anti-TNF Therapy.

INTRODUCTION: Studies suggest that the generation of durable T cell immunity following COVID-19 vaccination protects against severe disease. The aim of this study was to measure cell mediated immune response (CMIR) one to two months and six months after a third dose of a COVID-19 mRNA vaccine. METHODS: This prospective study (HERCULES) evaluated CMIR at 28-65 days (t1) after dose 2, 28-65 days (t2) (n=183) and six months (+/-45 days) (t3) (n=167) after a third dose of an mRNA COVID-19 vaccine. A small cohort had blood available 28-65 days (t4) (n=55) after a fourth dose. Primary outcomes were CMIR at (t2) and (t3). Secondary outcomes included the effect of immunosuppressing IBD medications on CMIR and response at (t4). RESULTS: All patients had measurable CMIR at all time points. CMIR increased at t2 compared to t1 (median 1467 responding cells per million (interquartile range (IQR) 410-5971) vs 313 (94-960) p< 0.001). There was no significant waning when comparing t2 vs t3 or significant boosting at t4. Those on anti-TNF monotherapy had a higher CMIR compared to those not on this therapy at t2 (4132 ( IQR 1136-8795) vs. 869 (IQR 343-3221) p <0.001) and t3 (2843 (IQR 596-6459) vs 654 (IQR 143-2067) p<0.001). In univariable analysis, anti-TNF monotherapy was associated with a higher CMIR at t2 (p< 0.001) and t3 (p< 0.001) and confirmed in a multivariable model (p< 0.001). CONCLUSION: 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.

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.

Estimating the cost of university-based outbreaks of serogroup B meningococcal disease with different pre-matriculation vaccination policies in the United States.

Objective: We developed an Excel-based cost calculator to assess the economic burden of university-based Neisseria meningitidis serogroup B (MenB) outbreaks. Participants: Hypothetical university with 6,354 students. Methods: Total societal costs of outbreak were estimated for three MenB pre-matriculation immunization policies-vaccination required, vaccination recommended, and no vaccine policy-under three different cost assumptions (low/mid-range/high cost). Results: Mid-range cost estimates of an outbreak under "no policy" were $2.60 and $2.70 million (of which 35% were incurred by the university) if targeting all undergraduates for mass vaccination with a two-/three-dose vaccine, respectively. The "required" and "recommended" policies lowered the burden to $2.17-$2.18 million and $2.34-$2.39 million, respectively. For a larger university with 40,000 students, costs were almost $9 million for a two-dose vaccine with "no policy" in place. Conclusions: The economic burden of a university MenB outbreak is substantial, but could be mitigated by a pre-matriculation MenB vaccination requirement or recommendation.

Characteristics of U.S. older adult medicare beneficiaries receiving the influenza vaccination at retail pharmacies.

Background: Pharmacy-provided influenza vaccination services have become more prevalent among the older adult population. However, little is known about the characteristics of older adults associated with receiving the influenza vaccination at retail pharmacies and how these associated characteristics have changed. Objective: To examine characteristics of older adults associated with use of retail pharmacy-provided influenza vaccination services and how the characteristics changed between 2009 and 2015. Methods: The study used a retrospective, cross-sectional design with data from the 2009 and 2015 Medicare Current Beneficiary Survey. Older adults aged 65 and older who completed a community questionnaire and received the influenza vaccination during the previous winter were identified. Andersen's Behavioral Model of Health Services Use was the conceptual framework for inclusion of the population characteristics. A multivariable log-binomial regression was performed to estimate the association between the population characteristics and use of pharmacy-provided vaccination service, and the relative change in associations between 2009 and 2015. Survey weights were applied in all analyses. Results: The results showed older adults who were non-Hispanic black (compared to non-Hispanic white), who did not have secondary private insurance (compared to those who had), who did not have physician office visit (compared to those who had) and who lived in non-metro area (compared to those who lived in metro area) had become more likely to use pharmacy-provided influenza vaccination services in 2015 than in 2009. Conclusions: Pharmacy-provided influenza vaccination services appear to reduce access barriers for racially and socioeconomically disadvantaged older adults. Findings could help inform not only the retail pharmacies that provide vaccination services to better outreach to potential target populations but also policy makers about the disadvantaged populations that would benefit from the vaccination services provided by retail pharmacies.

Higher Cell-Mediated Immune Responses in Patients With Inflammatory Bowel Disease on Anti-TNF Therapy After COVID-19 Vaccination.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) on immunosuppressive therapies may have a blunted response to certain vaccines, including the messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines. However, few studies have evaluated the cell-mediated immune response (CMIR), which is critical to host defense after COVID-19 infection. The aim of this study was to evaluate the humoral immune response and CMIR after mRNA COVID-19 vaccination in patients with IBD. METHODS: This prospective study (HERCULES [HumoRal and CellULar initial and Sustained immunogenicity in patients with IBD] study) evaluated humoral immune response and CMIR after completion of 2 doses of mRNA COVID-19 vaccines in 158 IBD patients and 20 healthy control (HC) subjects. The primary outcome was the CMIR to mRNA COVID-19 vaccines in patients with IBD. The secondary outcomes were a comparison of (1) the CMIR in patients with IBD and HC subjects, (2) CMIR and humoral immune response in all participants, and (3) correlation between CMIR and humoral immune response. RESULTS: The majority (89%) of patients with IBD developed a CMIR, which was not different vs HC subjects (94%) (P = .6667). There was no significant difference (P = .5488) in CMIR between immunocompetent (median 255 [interquartile range, 146-958] spike T cells per million peripheral blood mononuclear cells) and immunosuppressed patients (median 377 [interquartile range, 123-1440]). There was no correlation between humoral and cell-mediated immunity after vaccination (P = .5215). In univariable analysis, anti-tumor necrosis factor therapy was associated with a higher CMIRs (P = .02) and confirmed in a multivariable model (P = .02). No other variables were associated with CMIR. CONCLUSIONS: Most patients with IBD achieved CMIR to a COVID-19 vaccine. Future studies are needed evaluating sustained CMIR and clinical outcomes.

Antibody and T cell responses to coronavirus disease 2019 vaccines in patients with inflammatory bowel disease do not correlate. Most patients with inflammatory bowel disease mount a T cell response despite being on biologic therapies, those on anti-tumor necrosis factor may have a higher T cell response. Anti-tumor necrosis factor therapy has been associated with a lower antibody response to coronavirus disease 2019 vaccines, but the T cell response is augmented.

High but Inequitable COVID-19 Vaccine Uptake Among Rehabilitation Patients.

INTRODUCTION: There is a paucity of studies evaluating vaccine uptake in adults with neurological and musculoskeletal medical conditions. We sought to evaluate the rates of COVID-19 vaccine uptake in patients seen in an outpatient rehabilitation clinic. METHODS: We conducted a retrospective, single center study of adults seen at an outpatient rehabilitation clinic from December 1, 2020, through June 30, 2021, with an active Wisconsin Immunization Registry record. The primary outcome was completion of a COVID-19 primary vaccine series. RESULTS: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P < 0.001) had higher odds of not completing a COVID-19 vaccination series. CONCLUSIONS: There was a high rate of COVID-19 vaccine uptake among patients seen in a rehabilitation clinic, though racial, ethnic, and geographic differences did exist. Further studies are needed to determine why these disparities exist and investigate interventions to increase vaccine uptake in these populations.

Uptake Rates of Three COVID-19 Vaccine Doses and Risk Factors for Incomplete Vaccination Among Patients With Inflammatory Bowel Disease Residing in Wisconsin: A Single-Center Cohort.

INTRODUCTION: Patients with inflammatory bowel disease on systemic corticosteroids may be at higher risk of adverse outcomes of COVID-19 infection, and vaccination is an essential preventive measure. Uptake of the original 2-dose COVID-19 messenger RNA (mRNA) primary vaccine series was previously high among patients with inflammatory bowel disease, while uptake of subsequent doses based on interval recommendations made by the Advisory Committee on Immunization Practice remains unknown. Herein, we evaluated uptake of 3 COVID-19 mRNA vaccine doses among patients with inflammatory bowel disease. METHODS: A total of 1012 patients were identified; 728 (71.9%) patients received 3 COVID-19 vaccine doses. Multivariable logistic regression revealed that younger age (odds ratio [OR] 1.02; 95% CI, 1.01 - 1.03; P = 0.001), rural status (OR 3.44; 95% CI, 2.17 - 5.56; P < 0.001), underrepresented minority status (OR 3.85; 95% CI, 1.89 - 7.69; P < 0.001), and absence of influenza vaccination (OR 8.17; 95% CI, 5.41 - 12.33; P < 0.001) were significantly associated with incomplete COVID-19 vaccination. RESULTS: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P < 0.001) had higher odds of not completing a COVID-19 vaccination series. CONCLUSIONS: Receipt of 3 COVID-19 mRNA vaccine doses is high overall among patients with inflammatory bowel disease. Younger age, underrepresented race/ethnicity, rural status, and lack of influenza vaccination are associated with incomplete COVID-19 vaccination.