GRJ has received grants or loans from the Wellcome Trust and ECCO; speaker fees from Takeda, Ferring, and Janssen; and support for attending meetings or travel from Ferring. was antibody responses against influenza/A H3N2 and A/H1N1, compared to controls, adjusting for age, prior vaccination, and interval between vaccination and sampling. Results Lower antibody responses against influenza A/H3N2 were observed in patients on infliximab (geometric mean ratio 0.35 [95% confidence interval 0.20C0.60], < 0.05 with two-tailed tests were considered significant. We included patients with missing clinical data in analyses for which they had data and specified the denominator for each variable. Antibody concentrations are reported as the geometric mean and standard deviation. Other continuous data are reported as a median and interquartile range, and discrete data as numbers and percentages, unless otherwise stated. For the univariate analysis comparing antibody levels among groups, a KruskalCWallis test was performed to test significance. Multivariable linear regression models were used to identify factors independently associated with antibody concentrations. Backward stepwise regression was used to test whether these variables were covariates: age, gender, ethnicity, body mass index [BMI], height, weight, smoking, IBD subtype, IBD disease activity (defined by patient-reported outcomes [assessed by PRO2 score]),17,18 vaccination against influenza in the previous [2020C2021] season, and interval in days between vaccination and blood sampling. Results are presented after exponentiation so that the models coefficients correspond to the geometric mean ratio associated with each covariate. The linearity, homogeneity of variance, collinearity, influential observations, and normality of residuals of each multivariate model were tested in R. Spearman correlation analysis was performed between antibodies against SARS-CoV-2 wild-type virus and each of the influenza strains measured in this study. We also performed a Spearman correlation analysis between the antibody Plantamajoside concentration with days after vaccination to show the antibody decay against time. 2.5. Ethical considerations and role of funders VIP is an investigator-led UK National Institute for Health Research COVID-19 study. Financial support was provided as an independent research grant by Pfizer Ltd. Pfizer Ltd had no role in study design, data collection or analysis, writing, or decision to submit for publication. Participants were included after providing informed, written consent. The Wales Research Ethics Committee 5 approved the study [REC reference 21/WA/0105] in March, 2021. The study was registered with the ISRCTN [No: 13495664] registry, and the protocol is available online at https://www.vipstudy.uk. 3. Results Between May 28, 2021 and March 29, 2022, 561 adult individuals were recruited to the VIP study, of whom 266 [213 IBD, 53 healthy controls; 166 vaccinated against influenza in the 2021C2022 season and 100 unvaccinated] were eligible for inclusion in the current analysis. Patients with IBD were established for at least 12 weeks on immunosuppressive treatment regimens, including infliximab [values <0.05]. Open in a separate window Figure 1. Antibody responses in healthy controls and patients with IBD against [A] A/H3N2 and [B] A/H1N1 [n?=?266]. Geometric means are shown with 95% confidence intervals. **p?0.01; ***p?0.001; ****p?0.0001. We then investigated how different immunosuppressive treatment regimens in patients with IBD Rabbit Polyclonal to CD40 impacted unadjusted influenza vaccine-induced antibody responses. Including 166 participants who were sampled 7C90 days after receiving the 2021 flu vaccine, different treatments displayed distinct attenuation in antibody responses [Figure 2]. Patients treated with infliximab (GM 46 475 [95% CI 29 940, 72 142], p?=?0.0056) or tofacitinib (41 198 [25 178, 67 411], p?=?0.013) had significantly lower GM antibody concentrations against A/Hong Kong H3N2 relative to healthy controls (105 289 [69 521, 159 459]; Figure 2A). Patients treated with infliximab (109 202 [65 370, 182 423], p?=?0.0008), thiopurine (164 733 [97 489, 278 359], p?=?0.049), combination of infliximab and thiopurine (141 684 [87 849, 228 509], p?=?0.012), and tofacitinib (94 322 [52 129, 170 665], Plantamajoside p?=?0.0016) had significantly lower GM antibody concentrations against A/Michigan H1N1 relative to controls (334 541 [232 892, 480 556]; Figure 2B). Unadjusted vaccine-induced antibody concentration data against B strains, stratified by IBD treatment regimen, are shown in Supplementary Figure S2. Open in a separate window Figure 2. Unadjusted vaccine-induced antibody responses Plantamajoside against [A] A/H3N2 and [B] A/H1N1 in patients with inflammatory bowel disease who received influenza vaccination in the 2021C2022 season, stratified by treatment group. Horizontal lines indicate geometric means. Time between influenza vaccination and blood sampling in this study was variable across the cohort. However, analysis of correlations between influenza vaccine-induced antibody concentrations and time in days between vaccination and blood sampling did not indicate a significant effect of antibody decay over the 83-day sampling window [Supplementary Figure S3]. Next, we performed multivariable linear regression to determine whether adjusting for participant age [a well-established factor in diminishing immune responses to.