Saha, Sumona

Abstract Background In infants that were exposed to biologics in utero, gastroenterology societal guidelines have either recommended against administration of the live rotavirus vaccine until 6-12 months of age or until serum biologic levels are undetectable. We performed a systematic review to evaluate the safety of rotavirus vaccination in biologic-exposed infants. Methods EMBASE, PubMed, Scopus, and Cochrane databases were searched from 2006 to 2024 for original data reporting on the safety of rotavirus vaccination in infants that were exposed to anti-tumor necrosis factors (TNFs) (ie, infliximab, adalimumab, golimumab, certolizumab) and non-TNF biologics (ie, vedolizumab, ustekinumab, rizankizumab, mirikizumab) in utero. Results A database search yielded 7185 screening results of which 10 studies met inclusion criteria. There were over 300 instances of rotavirus vaccination in biologic-exposed infants (n = 162 exposed to anti-TNFs, n = 142 exposed to non-TNF biologics). Biologic-exposed infants were not at an increased risk of severe adverse events or adverse events of any severity related to rotavirus vaccination. Conclusions Administration of the live rotavirus vaccine appears to be safe in biologic-exposed infants. As such, with careful examination of the risks and benefits, there may be a role for rotavirus vaccination in this population.

Abstract Background Extraintestinal manifestations (EIMs) of inflammatory bowel diseases (IBDs) are a common and debilitating feature of disease, occurring in up to 40% of patients with IBD, yet predicting who may develop them is difficult. The goal of our study was to better characterize which patients may be at highest risk of developing not only 1 EIM, but also multiple EIMs, across both diseases. Methods A retrospective study of participants enrolled in the SPARC IBD (Study of Prospective Adult Research Cohort with IBD) registry was performed, and demographic and clinical data were analyzed. A total of 1211 patients with data available on EIMs were included, and differences among variables with vs without EIMs were assessed. Results A total of 329 participants with at least 1 EIM were identified, compared with 882 participants without any EIMs. Crohn’s disease patients and women were more likely to have 2 or more EIMs (P = .005 and P ≤ .001, respectively). Participants with ocular manifestations were likeliest to have at least 2 EIMs (P ≤ .001). Even when diagnosis was controlled for, involvement of the right colon (P = .021) was predictive of IBD-associated arthritis across both diseases in a multivariate generalized linear model. Conclusions This is the first comprehensive large-cohort assessment of how EIMs relate to one another at the individual vs systems levels. Further, our analysis is the first to recognize specific locations of colon involvement associated with EIMs of IBD, regardless of IBD type. These results are important in identifying patients at risk of developing future EIMs and may help with risk stratification when choosing treatments.

Abstract 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.

Lay Summary Herein, we evaluated the humoral immunogenicity of a third coronavirus disease 2019 messenger RNA vaccine dose in patients with inflammatory bowel diseases. All patients displayed a humoral immune response, and median antibody concentrations were higher after the third dose than after completion of the 2-dose series.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at an increased risk of herpes zoster (HZ). HZ is caused by reactivation of the varicella zoster virus (VZV) and is prevented by strong VZV-specific cell-mediated immunity. The aim of our study was to evaluate whether patients with IBD had lower or equivalent protection compared with healthy controls (HCs) at age 50 years and older. METHODS: We performed a cross-sectional study at a single academic center and evaluated cellular and humoral immunity to VZV in patients with IBD at age 35–49 years vs HCs aged 50–59 years. All patients with IBD were on stable medication regimens for at least 3 months. VZV-specific cell-mediated immunity was measured via ELISPOT, and humoral immunity was measured via a quantitative VZV antibody enzyme-linked immunosorbent assay assay. RESULTS: Seventy-seven patients with IBD and 12 HCs were enrolled in the study. There was no significant difference in ELISPOT counts between patients with IBD and HCs ( P = 0.54). In addition, there was also no significant difference between ELISPOT counts in immunosuppressed patients with IBD (N = 45) and HCs ( P = 0.32). We also found no correlations between ELISPOT counts and age (Spearman rho 0.014; P = 0.90). Patients with IBD had similar IgG VZV antibody levels (median 19 mIU/mL; range 0.5–218) compared with HCs (median 23.5 mIU/mL (range 4–34); P = 0.54). DISCUSSION: Young patients with IBD have equivalent cellular and humoral immunity to VZV as healthy older adults in whom HZ immunization is recommended.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) on immune-modifying therapies may have a lower vaccine response to certain vaccines. The aim of our study was to evaluate humoral immunogenicity of mRNA coronavirus disease 2019 (COVID-19) vaccines among patients with IBD and healthy controls (HCs). METHODS: We performed a prospective study to evaluate humoral immunogenicity among patients with IBD and HCs after completion of mRNA COVID-19 vaccines. RESULTS: One hundred twenty-two patients with IBD and 60 HCs were enrolled. All HCs and 97% of patients with IBD developed antibodies. Antibody concentrations were lower in patients with IBD compared with those in HCs (median 31 vs 118 μg/mL; P < 0.001). Those who received the mRNA-1273 (Moderna) COVID-19 (median 38; interquartile range [IQR] 24–75 vs μg/mL) had higher antibody concentrations compared with those who received the Pfizer-BNT vaccine series (median 22; IQR 11–42 μg/mL; P < 0.001). Patients on immune-modifying therapy (median 26; IQR 13–50 μg/mL) had lower antibody concentrations compared with those who were on no treatment, aminosalicylates, or vedolizumab (median 59; IQR 31–75 μg/mL; P = 0.003). DISCUSSION: Almost all patients with IBD in our study mounted an antibody response. Future studies are needed in evaluating sustained humoral immunity and the impact of booster dosing in patients with IBD.

Abstract Background Clinical and molecular subcategories of inflammatory bowel disease (IBD) are needed to discover mechanisms of disease and predictors of response and disease relapse. We aimed to develop a study of a prospective adult research cohort with IBD (SPARC IBD) including longitudinal clinical and patient-reported data and biosamples. Methods We established a cohort of adults with IBD from a geographically diverse sample of patients across the United States with standardized data and biosample collection methods and sample processing techniques. At enrollment and at time of lower endoscopy, patient-reported outcomes (PRO), clinical data, and endoscopy scoring indices are captured. Patient-reported outcomes are collected quarterly. The quality of clinical data entry after the first year of the study was assessed. Results Through January 2020, 3029 patients were enrolled in SPARC, of whom 66.1% have Crohn’s disease (CD), 32.2% have ulcerative colitis (UC), and 1.7% have IBD-unclassified. Among patients enrolled, 990 underwent colonoscopy. Remission rates were 63.9% in the CD group and 80.6% in the UC group. In the quality study of the cohort, there was 96% agreement on year of diagnosis and 97% agreement on IBD subtype. There was 91% overall agreement describing UC extent as left-sided vs extensive or pancolitis. The overall agreement for CD behavior was 83%. Conclusion The SPARC IBD is an ongoing large prospective cohort with longitudinal standardized collection of clinical data, biosamples, and PROs representing a unique resource aimed to drive discovery of clinical and molecular markers that will meet the needs of precision medicine in IBD.