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The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs : a Swedish nationwide study (COVID-19-REUMA)

Frodlund, Martina ; Nived, Per LU ; Chatzidionysiou, Katerina ; Södergren, Anna ; Klingberg, Eva ; Hansson, Monica ; Ohlsson, Sophie LU orcid ; Pin, Elisa ; Bengtsson, Anders LU and Klareskog, Lars , et al. (2024) In Microbiology spectrum 12(4).
Abstract

UNLABELLED: Studies investigating the immunogenicity of additional COVID-19 vaccine doses in immunosuppressed patients with inflammatory rheumatic diseases (IRD) are still limited. The objective was to explore the antibody response including response to omicron virus subvariants (sBA.1 and sBS.2) after third and fourth COVID-19 vaccine doses in Swedish IRD patients treated with immunomodulating drugs compared to controls. Antibody levels to spike wild-type antigens (full-length protein and S1) and the omicron variants sBA.1 and sBA.2 (full-length proteins) were measured. A positive response was defined as having antibody levels over cut-off or ≥fourfold increase in post-vaccination levels for both antigens. Patients with arthritis,... (More)

UNLABELLED: Studies investigating the immunogenicity of additional COVID-19 vaccine doses in immunosuppressed patients with inflammatory rheumatic diseases (IRD) are still limited. The objective was to explore the antibody response including response to omicron virus subvariants (sBA.1 and sBS.2) after third and fourth COVID-19 vaccine doses in Swedish IRD patients treated with immunomodulating drugs compared to controls. Antibody levels to spike wild-type antigens (full-length protein and S1) and the omicron variants sBA.1 and sBA.2 (full-length proteins) were measured. A positive response was defined as having antibody levels over cut-off or ≥fourfold increase in post-vaccination levels for both antigens. Patients with arthritis, vasculitis, and other autoimmune diseases (
n = 414), and controls (
n = 61) receiving biologic/targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) with or without conventional synthetic DMARDs participated. Of these, blood samples were available for 370 patients and 52 controls after three doses, and 65 patients and 15 controls after four doses. Treatment groups after three vaccine doses were rituximab (
n = 133), abatacept (
n = 22), IL6r inhibitors (
n = 71), JAnus Kinase inhibitors (JAK-inhibitors) (
n = 56), tumor necrosis factor inhibitor (TNF-inhibitors) (
n = 61), IL12/23/17 inhibitors (
n = 27), and controls (
n = 52). The percentage of responders after three and four vaccine doses was lower in rituximab-treated patients (59% and 57%) compared to controls (100%) (
P < 0.001). After three doses, the percentage of responders in all other groups was 100%, including response to omicron sBA.1 and sBA.2. In rituximab-treated patients, higher baseline immunoglobulin G (IgG) and longer time-period between rituximab and vaccination predicted better response. In this Swedish nationwide study including IRD patients three and four COVID-19 vaccine doses were immunogenic in patients treated with IL6r inhibitors, TNF-inhibitors, JAK-inhibitors, and IL12/23/17-inhibitors but not in rituximab. As >50% of rituximab patients responded to vaccines including omicron subvariants, these patients should be prioritized for additional vaccine doses.

IMPORTANCE: Results from this study provide further evidence that additional doses of COVID-19 vaccines are immunogenic and result in satisfactory antibody response in a majority of patients with inflammatory rheumatic diseases (IRD) receiving potent immunomodulating treatments such as biological or targeted disease-modifying anti-rheumatic drugs (DMARDs) given as monotherapy or combined with traditional DMARDs. We observed that rituximab treatment, both as monotherapy and combined with csDMARDs, impaired antibody response, and only roughly 50% of patients developed a satisfactory antibody response including response to omicron subvariants after the third vaccine. In addition, higher IgG levels at the last rituximab course before the third vaccine dose and a longer time after the last rituximab treatment increased the chance of a satisfactory antibody response. These results indicate that rituximab-treated patients should be prioritized for additional vaccine doses.

CLINICAL TRIALS: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with number 2021-000880-63.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Microbiology spectrum
volume
12
issue
4
article number
e0298123
publisher
American Society for Microbiology
external identifiers
  • scopus:85189310992
  • pmid:38441463
ISSN
2165-0497
DOI
10.1128/spectrum.02981-23
language
English
LU publication?
yes
id
3a524389-e7ce-4bb7-9616-39eba181556d
date added to LUP
2024-03-19 23:42:29
date last changed
2024-04-26 14:52:06
@article{3a524389-e7ce-4bb7-9616-39eba181556d,
  abstract     = {{<p>UNLABELLED: Studies investigating the immunogenicity of additional COVID-19 vaccine doses in immunosuppressed patients with inflammatory rheumatic diseases (IRD) are still limited. The objective was to explore the antibody response including response to omicron virus subvariants (sBA.1 and sBS.2) after third and fourth COVID-19 vaccine doses in Swedish IRD patients treated with immunomodulating drugs compared to controls. Antibody levels to spike wild-type antigens (full-length protein and S1) and the omicron variants sBA.1 and sBA.2 (full-length proteins) were measured. A positive response was defined as having antibody levels over cut-off or ≥fourfold increase in post-vaccination levels for both antigens. Patients with arthritis, vasculitis, and other autoimmune diseases (<br>
 n = 414), and controls (<br>
 n = 61) receiving biologic/targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs) with or without conventional synthetic DMARDs participated. Of these, blood samples were available for 370 patients and 52 controls after three doses, and 65 patients and 15 controls after four doses. Treatment groups after three vaccine doses were rituximab (<br>
 n = 133), abatacept (<br>
 n = 22), IL6r inhibitors (<br>
 n = 71), JAnus Kinase inhibitors (JAK-inhibitors) (<br>
 n = 56), tumor necrosis factor inhibitor (TNF-inhibitors) (<br>
 n = 61), IL12/23/17 inhibitors (<br>
 n = 27), and controls (<br>
 n = 52). The percentage of responders after three and four vaccine doses was lower in rituximab-treated patients (59% and 57%) compared to controls (100%) (<br>
 P &lt; 0.001). After three doses, the percentage of responders in all other groups was 100%, including response to omicron sBA.1 and sBA.2. In rituximab-treated patients, higher baseline immunoglobulin G (IgG) and longer time-period between rituximab and vaccination predicted better response. In this Swedish nationwide study including IRD patients three and four COVID-19 vaccine doses were immunogenic in patients treated with IL6r inhibitors, TNF-inhibitors, JAK-inhibitors, and IL12/23/17-inhibitors but not in rituximab. As &gt;50% of rituximab patients responded to vaccines including omicron subvariants, these patients should be prioritized for additional vaccine doses.<br>
 </p><p>IMPORTANCE: Results from this study provide further evidence that additional doses of COVID-19 vaccines are immunogenic and result in satisfactory antibody response in a majority of patients with inflammatory rheumatic diseases (IRD) receiving potent immunomodulating treatments such as biological or targeted disease-modifying anti-rheumatic drugs (DMARDs) given as monotherapy or combined with traditional DMARDs. We observed that rituximab treatment, both as monotherapy and combined with csDMARDs, impaired antibody response, and only roughly 50% of patients developed a satisfactory antibody response including response to omicron subvariants after the third vaccine. In addition, higher IgG levels at the last rituximab course before the third vaccine dose and a longer time after the last rituximab treatment increased the chance of a satisfactory antibody response. These results indicate that rituximab-treated patients should be prioritized for additional vaccine doses.</p><p>CLINICAL TRIALS: EudraCT (European Union Drug Regulating Authorities Clinical Trials Database) with number 2021-000880-63.</p>}},
  author       = {{Frodlund, Martina and Nived, Per and Chatzidionysiou, Katerina and Södergren, Anna and Klingberg, Eva and Hansson, Monica and Ohlsson, Sophie and Pin, Elisa and Bengtsson, Anders and Klareskog, Lars and Kapetanovic, Meliha}},
  issn         = {{2165-0497}},
  language     = {{eng}},
  number       = {{4}},
  publisher    = {{American Society for Microbiology}},
  series       = {{Microbiology spectrum}},
  title        = {{The serological immunogenicity of the third and fourth doses of COVID-19 vaccine in patients with inflammatory rheumatic diseases on different biologic or targeted DMARDs : a Swedish nationwide study (COVID-19-REUMA)}},
  url          = {{http://dx.doi.org/10.1128/spectrum.02981-23}},
  doi          = {{10.1128/spectrum.02981-23}},
  volume       = {{12}},
  year         = {{2024}},
}