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.

Immunogenicity and safety of a three-dose SARS-CoV-2 vaccination strategy in patients with immune-mediated inflammatory diseases on immunosuppressive therapy

“…The prospective, observational Norwegian study of vaccine response to COVID-19 vaccines (Nor-vaC) is an ongoing longitudinal observational study conducted at two Norwegian IMID centres; the Division of Rheumatology at Diakonhjemmet Hospital (DH) and the Department of Gastroenterology at Akershus University Hospital (AHUS). 7 Adult patients (aged ≥18 years) with RA, SpA, PsA, UC or CD who used any of the relevant immunosuppressive medications ( online supplemental appendix 1 ) were identified by the hospital records and consecutively recruited into the study prior to the initiation of the national vaccination programme in February 2021. Healthcare workers from DH, AHUS and Oslo University Hospital (OUH) were recruited as healthy controls ( online supplemental appendix 2 ).…”

The persistence of anti-Spike antibodies following two SARS-CoV-2 vaccine doses in patients on immunosuppressive therapy compared to healthy controls—a prospective cohort study

“…We have previously reported that patients with IMIDs have an attenuated SARS-CoV-2 vaccine response compared to healthy controls at the first assessment after a standard two-dose regimen [ 12 , 15 ]. We now report continued low antibody levels in this 4-month follow-up study.…”

“…To explore the impact of age on antibody decline, an agestratified multivariable regression was performed. [15][16][17][18][19][20][21][22][23][24] and 97 days [87-105] after second vaccine dose), and were included in the present study (Additional file 1: Fig. S3).…”

“…SARS-CoV-2 vaccines have a proven efficacy in the general population, and antibody levels correlate to the degree of clinical protection against COVID-19 disease [1][2][3]. However, recent data suggest that patients with immune-mediated inflammatory disease (IMID) treated with certain immunosuppressants have an impaired serological response following vaccination, with lower anti-Spike antibody levels than the general population [4][5][6][7][8][9][10][11][12][13][14][15]. The impairment of the immune response varies between the different immunosuppressive therapies, where some seemingly do not affect the humoral response, while other drugs, such as rituximab and abatacept, have been found to profoundly reduce vaccine response [12,[15][16][17].…”

“…Use of immunosuppressive therapies combined with a dysregulated immune system and an increased frequency of several co-morbidities increases the susceptibility to serious infections and vulnerability to adverse outcomes of infectious diseases in these patients [22][23][24]. There are, however, disparities between therapies regarding the degree of impact on the immune responses and thus the susceptibility to serious infections [12,15,17,25,26].…”