Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy

Abstract

Objective: Immunogenicity and safety following receipt of the standard SARS-CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS-CoV-2 vaccine in IMID patients receiving immunosuppressive therapy.

Methods: Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS-CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were performed prior to and 2-4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS-Cov-2 spike protein, were allotted a third vaccine dose.

Results: A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192-4,191) than in controls (median 3,355 AU/ml [IQR 896-7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA-1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable.

Conclusion: IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

Trial registration: ClinicalTrials.gov NCT04798625.

Figure 1

Violin plots of probability densities, smoothed by a kernel density estimator, of IgG antibody levels against the receptor‐binding domain of SARS–CoV‐2 spike protein (anti‐RBD) after the standard 2‐dose SARS–CoV‐2 vaccination regimen among healthy controls (CTRL) and among patients with immune‐mediated inflammatory disease (IMID) stratified by immunosuppressive therapy. Points denote participants, and solid orange lines show group medians. P values show comparisons to CTRL and were calculated by Mann‐Whitney U test. TNFi mono = tumor necrosis factor inhibitor monotherapy; TNFi combo = TNFi combination therapy; MTX = methotrexate; VDZ = vedolizumab; TCZ = tocilizumab; UST = ustekinumab; ABA = abatacept; SCK = secukinumab. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.42153/abstract.

Figure 2

Anti‐RBD levels after receipt of a third SARS–CoV‐2 vaccine dose among IMID patients with a weak response to the standard 2‐dose vaccination regimen. Levels were measured 2–4 weeks after the second and third vaccine doses. Horizontal dotted lines indicate the serologic response cutoff (70 arbitrary units per milliliter [AU/ml]). Orange dots and lines indicate anti‐RBD levels in individual patients with inflammatory bowel disease; blue dots and lines indicate levels in individual patients with inflammatory joint disease. P values were calculated by Wilcoxon paired test. RA = rheumatoid arthritis; PsA = psoriatic arthritis; SpA = spondyloarthritis; obs. = observations; IQR = interquartile range; CD = Crohn's disease; UC = ulcerative colitis; miscellaneous = vedolizumab, ustekinumab, tocilizumab, secukinumab, or azathioprine (see Figure 1 for other definitions).

Figure 3

Type and duration of adverse events reported after doses 1 (blue bars) and 2 (orange bars) of SARS–CoV‐2 vaccine among patients with immune‐mediated inflammatory disease (IMID) and healthy controls and after dose 3 (gray bars) among IMID patients who had a weak serologic response (defined as <70 arbitrary units per milliliter) to doses 1 and 2. Adverse events were reported for all patients and a subset of 246 healthy controls described in Patients and Methods. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.42153/abstract.