Immunogenicity and Safety of Recombinant Herpes Zoster Vaccine in Patients With Inflammatory Bowel Disease on Vedolizumab or Anti-Tumor Necrosis Factor Therapy

Abstract

Introduction: Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster and should receive the recombinant herpes zoster vaccine (RZV). We sought to assess the immunogenicity and safety of RZV series in patients receiving anti-tumor necrosis factor (TNF) therapy compared with those receiving vedolizumab.

Methods: This single-center prospective study enrolled patients with IBD on vedolizumab or anti-TNF monotherapy receiving RZV. Primary outcome assessed cell-mediated immunity (CMI) differences between groups postvaccination. Secondary outcomes included humoral response, sustained immunity, and safety monitoring for adverse events and IBD flares. Assessments occurred at baseline, 30, 240, and 425 days postvaccination. Statistical analyses included nonparametric Mann-Whitney U tests for between-group comparisons and Wilcoxon signed-rank tests for within-group changes, with significance set at P < 0.05.

Results: Thirty-three patients enrolled (16 vedolizumab, 17 anti-TNF). CMI responses increased postvaccination in both groups (median 56 cells/million [interquartile range {IQR} 21-102] vs 33 cells/million [IQR 11-73]; P = 0.13), with no significant difference between treatment groups. Both groups showed strong antibody responses to vaccination (preimmunization median: 349.9 mIU/mL [IQR 276.8-402.5] vs 90-day median: 605.0 mIU/mL [IQR 525.6-641.0]; P < 0.001). CMI responses remained elevated at both day 240 and 425 assessments. Antibody levels remained elevated through day 425 (549.1 mIU/mL, IQR 516.1-585.6), substantially higher than prevaccination levels. No IBD flares occurred; most adverse events were mild and transient.

Discussion: RZV demonstrated robust immunogenicity and favorable safety profile in patients with IBD receiving either vedolizumab or anti-TNF therapy. Both cellular and humoral immune responses persisted through 425 days postvaccination.

Trial registration: ClinicalTrials.gov NCT03798691.

Keywords: Crohn's disease; biologic therapy; ulcerative colitis; vaccination.

Graphical abstract

Figure 1.

Patient enrollment and study flow. Consolidated Standards of Reporting Trials diagram showing enrollment and follow-up of patients with IBD receiving vedolizumab (n = 16) or anti-TNF (n = 17) monotherapy who received the recombinant zoster vaccine. Four patients were excluded: one before vaccination, one after first dose due to pandemic disruption, one unable to attend follow-up visits, and one who withdrew after completing vaccination. Thirty participants completed the primary end point evaluation at 90 days, with 29 completing the 1-year follow-up. IBD, inflammatory bowel disease; TNF, tumor necrosis factor.

Figure 2.

Humoral and cellular immunogenicity of RZV vaccine series in patients with IBD on vedolizumab or anti-TNF monotherapy. Cell-mediated and antibody immune responses were measured before and 30, 240, and 425 days post vaccine series completion. Cell-mediated immune responses at each time point. ELISPOT was used to measure the number of cells that made an interferon-gamma (IFN-γ) response to varicella virus antigen. Antibody responses were measured by ELISA. (a) Cell-mediated immune response for all participants. CMI responses increased after vaccination, although the difference did not reach statistical significance (prevaccine [n = 18] median 33 cells/million, IQR 11–73 vs postvaccine [n = 24] median 56 cells/million, IQR 21–102; P = 0.13). (b) Cell-mediated immune response for participants treated with vedolizumab. Median number of responding cells was 33 cells/million prevaccine and 1 month postvaccine series. The CMI responses were 71 and 83 cells per million at 240 and 425 days showing sustained responses. (c) Cell-mediated immune response for participants treated with anti-TNF-α. Median number of responding cells was 33 cells/million prevaccine and 50 cells/million 1 month post vaccine series. The CMI responses were 80 and 80 cells per million at 240 and 425 days showing sustained responses. (d) Antibody responses for all participants. Antibody concentrations increased from baseline (median 349.9 mIU/mL) to 605.0 mIU/mL at 30 days post = vaccine series. The antibody responses were 552.2 and 549.1 mIU/mL at 240 and 425 days showing sustained responses. (e) Antibody responses for participants treated with vedolizumab. Antibody concentrations increased from baseline (median 337.0 mIU/mL) to 582.9 mIU/mL (P = 0.002) at 30 days postvaccine series. The antibody responses were 494.0 and 576.8 mIU/mL at 240 and 425 days showing sustained responses. (f) Antibody responses for participants treated with anti-TNF-α agent. Antibody concentrations increased from baseline (median 353.6 mIU/mL) to 624.0 mIU/mL (P = 0.001) at 30 days postvaccine series. The antibody responses were 564.6 and 541.5 mIU/mL at 240 and 425 days showing sustained responses (IQR 278.1–368.8 vs post 624.0; IQR 567.1–651.1; P = 0.007 and tumor necrosis factor α agent median antibody concentration pre 337.0 mIU/mL; IQR 273.0–453.3 vs post 582.9 mIU/mL; IQR 507.3–625.2; P < 0.001). CMI, cell-mediated immunity; ELISPOT, enzyme-linked immunospot; IBD, inflammatory bowel disease; IQR, interquartile range; RZV, recombinant herpes zoster vaccine; TNF, tumor necrosis factor.

Figure 3.

Adverse events after RZV vaccination in patients with IBD on biologic therapy. The figure compares adverse event profiles between patients with IBD receiving vedolizumab or anti-TNF monotherapy after Shingrix (RZV) vaccination. (a) (dose 1) and (b) (dose 2) display the percentage of participants experiencing local reactions (injection site pain/soreness, pruritus, erythema, swelling, warmth) and systemic effects (headaches, fever/chills, fatigue, myalgias) after each dose, with severity graded from 1 (mild, green) to 4 (potentially life-threatening, red). Local adverse effects were common in both treatment groups, with pain being most frequent. Systemic adverse events were more pronounced after the second dose, particularly in the vedolizumab group. These data are from a prospective trial evaluating RZV immunogenicity in patients with IBD on biologic therapy. IBD, inflammatory bowel disease; RZV, recombinant herpes zoster vaccine; TNF, tumor necrosis factor.