Citations

Abstract Background Children with inflammatory bowel disease (IBD) may have diminished serologic response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and increased risk for subsequent severe coronavirus disease 2019 (COVID-19) infection. We sought to describe outcomes among those who developed SARS-CoV-2 infection following vaccination, characterize SARS-CoV-2 antibodies 1 year post-vaccination, and identify factors associated with durable serologic response. Methods We recruited children with IBD who received ≥2 doses of SARS-CoV-2 vaccine and prospectively collected data on (1) demographics, IBD characteristics, and therapy and (2) SARS-CoV-2 vaccination, testing, and infection symptoms. Serum was obtained for measurement of anti-receptor-binding domain IgG antibodies following a 2-part immunization at 12 and 52 weeks. Results We enrolled 298 participants (mean age 11.9 ± 3.82, 50% female, 67% Crohn’s disease). Symptomatic COVID-19 infection after vaccination occurred in half of the participants, although only 2 (1%) required hospitalization. Anti-tumor necrosis factor alpha (TNF-α) was associated with higher likelihood of symptomatic COVID-19 infection, with an adjusted hazard ratio of 2.7 (95% CI, 1.5-5.0; P = .001). Nearly all participants (99%) had detectable antibody at Week 52. Children aged 1-5 years had lower 52-week antibody level compared to older children (P = .04), as did those on anti-TNF-α therapy (P = .007) and those who received only 2 vaccine doses prior to Week 52 (P < .001). Conclusions SARS-CoV-2 vaccination provides lasting serologic response and protection against severe COVID-19 for most children with IBD, despite the use of lower vaccine doses in younger children and wide-ranging classes of immunosuppressive therapies.

AbstractChildren with very early onset inflammatory bowel disease (VEO‐IBD) may respond differently to coronavirus disease 2019 (COVID‐19) immunization compared to healthy children or other patients with IBD. We recruited children with VEO‐IBD <6 years of age and younger following receipt of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccine. Demographics, IBD characteristics, medication use, adverse events (AEs) and IBD exacerbations were collected. Blood draws (optional) were obtained for measurement of antireceptor binding domain (RBD) IgG antibodies following vaccination. Of 41 participants, none required emergency department visit or hospitalization due to AE, and only one experienced IBD exacerbation. Detectable antibody was present in 19/19 participants who provided blood sample; 6/7 participants (86%) had durable humoral response 12 months postvaccination. Children with VEO‐IBD experience robust humoral immune response to COVID‐19 immunization. Severe AEs were rare. These findings provide reassurance that children with VEO‐IBD respond well and safely to SARS‐CoV‐2 vaccination.

INTRODUCTION: Children with inflammatory bowel disease (IBD) may respond differently to COVID-19 immunization as compared with healthy children or adults with IBD. Those younger than 12 years receive a lower vaccine dose than adults. We sought to describe the safety and humoral immune response to COVID-19 vaccine in children with IBD. METHODS: We recruited children with IBD, ages 5–17 years, who received ≥ 2 doses of the BNT162b2 vaccine by a direct-to-patient outreach and at select sites. Patient demographics, IBD characteristics, medication use, and vaccine adverse events were collected. A subset of participants had quantitative measurement of anti-receptor binding domain IgG antibodies after 2-part immunization. RESULTS: Our study population included 280 participants. Only 1 participant required an ED visit or hospitalization because of an adverse event. Of 99 participants who underwent anti-receptor binding domain IgG antibody measurement, 98 had a detectable antibody, with a mean antibody level of 43.0 μg/mL (SD 67) and a median of 22 μg/mL (interquartile range 12–38). In adjusted analyses, older age ( P = 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone ( P = 0.005) were associated with a decreased antibody level. Antibody response in patients treated with antitumor necrosis factor combination vs monotherapy was numerically lower but not significant. DISCUSSION: Humoral immune response to COVID-19 immunization in children with IBD was robust, despite a high proportion of this pediatric cohort being treated with immunosuppressive agents. Severe vaccine-related AEs were rare. Overall, these findings provide a high level of reassurance that pediatric patients with IBD respond well and safely to SARS-CoV-2 vaccination.

Lay SummaryWe demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.

Background:Research on the utilization and effectiveness of antitumor necrosis factor (TNF) biologics in children with very early onset inflammatory bowel disease (VEOIBD) is urgently needed. Here we describe anti‐TNF use and durability in a multicenter cohort.Methods:We performed a retrospective cohort study of patients diagnosed with VEOIBD (<6 years) between 2008 and 2013 at 25 North American centers. We performed chart abstraction at diagnosis and 1, 3, and 5 years after diagnosis. We examined the rate of initiation and durability of infliximab and adalimumab and evaluated associations between treatment durability and the following covariates with multivariate Cox proportional hazard regression: age at diagnosis, sex, disease duration, disease classification, and presence of combined immunomodulatory treatment versus monotherapy.Results:Of 294 children with VEOIBD, 120 initiated treatment with anti‐TNF therapy and 101 had follow‐up data recorded [50% Crohn disease (CD), 31% ulcerative colitis (UC), and 19% IBD unclassified (IBD‐U)]. The cumulative probability of anti‐TNF treatment was 15% at 1 year, 30% at 3 years, and 45% at 5 years from diagnosis; 56 (55%) were treated between 0 and 6 years old. Anti‐TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years. The most common reason for discontinuation of anti‐TNF were loss of response in 24 (57%) children. Children with UC/IBD‐U had lower durability than those with CD (hazard ratio [HR] 0.17; 95% confidence interval [CI], 0.06–0.51; P = 0.001).Conclusions:Utilization and durability of anti‐TNF in VEOIBD is relatively high and comparable with older children. Having Crohn disease (compared with UC/IBD‐U) is associated with greater durability.

Abstract Background Severe acute respiratory syndrome coronavirus 2 vaccination is recommended for all individuals with inflammatory bowel disease (IBD), including those on immunosuppressive therapies; however, little is known about vaccine safety and efficacy in these patients or the impact of vaccination on IBD disease course. Methods We evaluated coronavirus disease 2019 (COVID-19) vaccine–related adverse events (AEs) and the effect of vaccination on IBD disease course among participants in the PREVENT-COVID (Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID) study, a prospective, observational cohort study. Localized and systemic reactions were assessed via questionnaire. Disease flare was defined by worsening IBD symptoms and change in IBD medications. Outcomes were stratified by vaccine type and IBD medication classes. Results A total of 3316 individuals with IBD received at least 1 COVID-19 vaccine. Injection site tenderness (68%) and fatigue (46% dose 1, 68% dose 2) were the most commonly reported localized and systemic AEs after vaccination. Severe localized and systemic vaccine-related AEs were rare. The mRNA-1273 vaccine was associated with significantly greater severe AEs at dose 2 (localized 4% vs 2%, systemic 15% vs 10%; P &lt; .001 for both). Prior COVID-19 infection, female sex, and vaccine type were associated with severe systemic reactions to dose 1, while age &lt;50 years, female sex, vaccine type, and antitumor necrosis factor and vedolizumab use were associated with severe systemic reactions to dose 2. Overall rates (2%) of IBD flare were low following vaccination. Conclusions Our findings provide reassurance that the severe acute respiratory syndrome coronavirus 2 vaccine is safe and well tolerated among individuals with IBD, which may help to combat vaccine hesitancy and increase vaccine confidence.

Abstract Background The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. Methods We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. Results The study population included 269 children (105 [39%] Crohn’s disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9–5.2). Most (94%) Crohn’s disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn’s disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Conclusions Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%–15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.