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 mg/mL (SD 67) and a median of 22 mg/mL (interquartile range 12-38). In adjusted analyses, older age (P 5 0.028) and antitumor necrosis factor monotherapy compared with immunomodulators alone (P 5 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 vaccinerelated 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.

Background Current recommendations in many countries support additional COVID-19 vaccine doses in patients with inflammatory bowel disease (IBD) who are treated with immunosuppressants, yet real-world data on the effectiveness and safety of additional vaccine doses is lacking. We sought to quantify the humoral immune response to an additional vaccine dose in patients with IBD. Methods We performed a direct-to-patient, internet-based cohort study of patients with IBD in the United States who have received any SARS-CoV-2 vaccine granted EUA. Participants completed baseline and follow-up surveys and had blood work obtained approximately 8 weeks following completion of the initial vaccination series and 6 weeks following administration of an additional vaccine dose. We performed quantitative measurement of anti-receptor binding domain (RBD) IgG antibodies specific to SARS-CoV-2 using the LabCorp Cov2Quant IgG™ assay. Results A total of 659 participants were included [415 participants (63%) initially received BNT162b2, 243 participants (37%) initially received mRNA-1273, and 5 participants (1%) initially received Ad26.COV2.S]. Demographic, clinical, and treatment characteristics of the study population are provided in Table 1. Over 98% of those receiving an initial mRNA vaccine received the same type additional dose. Whereas 93% had detectable antibody after the initial vaccination series, 99.5% had detectable antibodies following an additional dose. Mean (SD) increase in antibody level was 61 ug/mL (103) in those receiving BNT162b2 and 78 ug/mL (143) for those receiving mRNA-1273 (Figure 1). Importantly, of 47 of patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose. Additional vaccination was generally well tolerated in this population, with 44%, 24%, 25%, and 6% reporting no, mild, moderate, and severe side effects respectively. Conclusion These findings demonstrate robust immunogenicity to additional doses of SARS-CoV-2 vaccine, even amongst patients with undetectable antibody following the initial series. Adverse event rates were low. These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression.

Background Patients with inflammatory bowel disease (IBD) may be at risk for development of COVID-19 infection due to innate immune dysfunction and/or immunosuppressive medication use. We sought to 1) evaluate the incidence of COVID-19 infection in a large, U.S. cohort of patients with IBD and 2) evaluate associations between demographic, clinical, and treatment-related factors and the development of COVID-19 infection. Methods Participants in 3 adult IBD studies sponsored by the Crohn’s & Colitis Foundation, IBD Partners, IBD QORUS (Improving the Quality of Care for Adults with Inflammatory Bowel Disease), and SPARC IBD (Study of a Prospective Adult Research Cohort with IBD), were invited to participate in a prospective, direct-to-patient cohort study about COVID-19 from April 23, 2020 until August 30, 2021. Each cohort received online surveys with questions on comorbidities, medication utilization and development of laboratory confirmed COVID-19 at times 0, 2, 4, 6, 8 weeks and then every 6 months. We calculated the incidence rate of COVID-19 and performed bivariate and multivariate analyses to describe associations between age, immunosuppression use, obesity, and race on the development of COVID-19. Results A total of 3953 patients with IBD were followed for a mean duration of 212 days (SD 157). Demographic, clinical and treatment factors are shown in Table 1. A total of 103 individuals developed COVID-19 during follow up (2.6%, rate of 45 per 1,000 person-years). Severity of infection was generally mild. Clinical characteristics were similar among those who developed COVID-19 as compared to not. African American race was associated with incident COVID-19 infection (OR 3.37, 95% CI 1.18–9.59). Immunosuppression use was not associated with development of COVID-19 (OR 1.19, 95% CI 0.72–1.75), nor was age (OR 1.00, 95% CI 0.99–1.02), nor obesity (OR 1.01, 95% CI 0.61–1.66). Conclusion The overall incidence of COVID-19 infection among this large U.S. cohort of IBD patients was relatively low. Immunosuppression use did not increase the risk of development of COVID-19. Therapeutic management of IBD should not be altered to prevent a risk of developing COVID-19.

Background Inflammatory bowel disease (IBD) and estrogen-based contraceptives both increase thromboembolism risk, leading gastroenterologists to recommend long-acting reversible contraceptives (LARCs) over estrogen-based methods for women with IBD. No study has evaluated whether young women with IBD follow this guidance, especially as many patients lack awareness of estrogen-related risks, and young women generally prefer estrogen-based methods. We evaluated contraceptive use patterns for young women with versus without IBD, including odds of estrogen-based contraceptive use. Methods Using the IQVIA Pharmetrics Plus Database, a United States (US) health insurance claims database, we identified US women ages 15-25 with ≥1 prescription contraceptive and ≥6 months continuous enrollment from enrollment start to first contraceptive code (intake period). We excluded patients with ≥1 hysterectomy/sterilization claim during intake. The independent variable was IBD diagnosis, defined as ≥3 codes for Crohn’s disease (CD) or ulcerative colitis (UC), 2 CD and/or UC codes and 1 IBD medication code, or 1 CD or UC code and 2 IBD medication codes during intake. The dependent variable was estrogen-based contraceptive use (estrogen-based contraceptive pill, patch, and ring) versus non-estrogen-based (progestin-only pill, injectable, implant, and intrauterine device [IUD]), based on the first contraceptive claim. We generated descriptive statistics for contraceptive sub-type and covariates stratified by IBD status and performed bivariate comparisons. Using multivariable logistic regression, we determined adjusted odds ratios (aOR) with 95% confidence intervals (CI) for estrogen-based contraceptive use, adjusting for age, region, year, and insurance. Results We identified 802,932 young women on contraceptives, of whom 1,083 had IBD. Demographics were similar across IBD status except more women with IBD had commercial insurance (Table). Use of the estrogen-based pill, patch, and ring was similar or marginally lower for women with IBD versus without IBD (67.6% vs 68.8%, 2.7 vs 3.1%, and 1.5 vs 1.4%). Women with IBD had a slightly higher proportion of implant use and similar IUD use versus those without IBD (16.1% vs 14.2%; 1.8% vs 1.7%,) (Table, Figure). After adjustment, young women with IBD were 0.82 times as likely to use estrogen-based contraceptives compared to those without IBD (aOR 0.82; 95% CI 0.71-0.94). Conclusion Young women with IBD on contraceptives are only slightly less likely to use estrogen-based methods as those without IBD, despite the recommendation for LARC over estrogen-based contraceptives in IBD. This finding suggests a need for reproductive health education efforts and contraceptive safety studies specific to young women with IBD.

Background Prior data have suggested that 5-aminosalicylates (5-ASA) may be associated with an increased risk of severe COVID-19 among inflammatory bowel disease (IBD) patients. We aimed to evaluate the association of 5-ASA with severe COVID-19 in a large cohort of IBD patients. Methods We analyzed data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) registry, a large, international database of IBD patients with confirmed COVID-19. The primary outcome was severe COVID-19, defined as intensive care unit admission, ventilator use, and/or death. Hospitalization due to COVID-19 was a secondary outcome. We performed multivariable regression modeling with a generalized estimating equation accounting for country as a random effect to analyze the association of 5-ASA with severe COVID-19. Models a priori included age, sex, race, disease phenotype (CD or UC/IBD-U), corticosteroid use, azathioprine/6-mercaptopurine use, TNF antagonist use, disease activity by physician global assessment, number of comorbidities, and days from SECURE-IBD inception to reporting. We constructed three models examining 5-ASA use as binary covariate using 1) all patients, 2) only patients on any biologic, and 3) only patients on TNF antagonists. Results 5,174 patients were included with 212 (4.1%) severe COVID-19 events. At the time of COVID-19 infection, 1,504 patients were taking 5-ASA. 5-ASA patients were older (mean age 44 vs. 38.3 years, p<0.001), more likely to have UC (70.7% vs. 27.7%, p<0.001), less likely to be in remission (49.6% vs. 57.2%, p<0.001), and more likely to have at least one comorbidity (33.6% vs. 26.7%, p<0.001) compared to patients not on 5-ASA. 3,325 patients were on any biologic and 2,216 were on a TNF antagonist. Among all patients, 5-ASA was not associated with severe COVID-19 (adjusted OR [aOR] 1.14, 95% confidence interval [CI] 0.86–1.52) (Table 1). Prior associations of age, comorbidities, TNF antagonists, and corticosteroids with severe COVID-19 were similar to prior analyses (Table 1). In analyses restricting to those on any biologic or only TNF antagonists, there was also no significant association between 5-ASA and severe COVID-19 (aOR 0.76, 95% CI 0.38–1.50 and aOR 0.99, 95% CI 0.43–2.32, respectively). Use of 5-ASA was not associated with risk of COVID-19 related hospitalization in any analysis. Conclusion In an analysis of updated data from the SECURE-IBD registry, 5-ASA use was not associated with worse outcomes among IBD patients with COVID-19.