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The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. A Swedish nationwide study (COVID19-REUMA)

Frodlund, Martina ; Nived, Per LU ; Chatzidionysiou, Aikaterini ; Södergren, Anna ; Klingberg, Eva ; Bengtsson, Anders LU ; Hansson, Monika ; Olsson, Sophie LU orcid ; Pin, Elisa and Klareskog, Lars , et al. (2023) In Vaccine 41(20). p.3247-3257
Abstract

OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).

METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins.

RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had... (More)

OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).

METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins.

RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p < 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p < 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p < 0,001).

CONCLUSIONS: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Vaccine
volume
41
issue
20
pages
3247 - 3257
publisher
Elsevier
external identifiers
  • pmid:37076360
  • scopus:85153107882
ISSN
1873-2518
DOI
10.1016/j.vaccine.2023.03.065
language
English
LU publication?
yes
additional info
Copyright © 2023. Published by Elsevier Ltd.
id
10bc8687-9432-42db-9607-503ba40e9e39
date added to LUP
2023-05-05 16:10:59
date last changed
2024-02-19 19:33:24
@article{10bc8687-9432-42db-9607-503ba40e9e39,
  abstract     = {{<p>OBJECTIVES: To elucidate antibody responses after the second and third dose of COVID-19 vaccine in patients with inflammatory rheumatic diseases (IRD) treated with biologic/targeted disease modifying anti-rheumatic drugs (b/ts DMARDs).</p><p>METHODS: Antibody levels to antigens representing spike full length protein and spike S1 were measured before vaccination, 2-12 weeks after the second dose, before and after the third dose using multiplex bead-based serology assay. Positive antibody response was defined as antibody levels over cut off (seropositivity) in seronegative individuals or ≥ 4-fold increase in antibodies in individuals seropositive for both spike proteins.</p><p>RESULTS: Patients (n = 414) receiving b/ts DMARDs (283 had arthritis, 75 systemic vasculitis and 56 other autoimmune diseases) and controls (n = 61) from five Swedish regions participated. Treatments groups were: rituximab (n = 145); abatacept (n = 22); Interleukin 6 receptor inhibitors [IL6i (n = 79)]; JAnus Kinase Inhibitors [JAKi (n = 58)], Tumour Necrosis Factor inhibitor [TNFi (n = 68)] and Interleukin12/23/17 inhibitors [IL12/23/17i (n = 42)]. Percentage of patients with positive antibody response after two doses was significantly lower in rituximab (33,8%) and abatacept (40,9%) (p &lt; 0,001) but not in IL12/23/17i, TNFi or JAKi groups compared to controls (80,3%). Higher age, rituximab treatment and shorter time between last rituximab course and vaccination predicted impaired antibody response. Antibody levels collected 21-40 weeks after second dose decreased significantly (IL6i: p = 0,02; other groups: p &lt; 0,001) compared to levels at 2-12 week but most participants remained seropositive. Proportion of patients with positive antibody response increased after third dose but was still significantly lower in rituximab (p &lt; 0,001).</p><p>CONCLUSIONS: Older individuals and patients on maintenance rituximab have an impaired response after two doses of COVID-19 vaccine which improves if the time between last rituximab course and vaccination extends and also after an additional vaccine dose. Rituximab patients should be prioritized for booster vaccine doses. TNFi, JAKi and IL12/23/17i does not diminished humoral response to primary and an additional vaccination.</p>}},
  author       = {{Frodlund, Martina and Nived, Per and Chatzidionysiou, Aikaterini and Södergren, Anna and Klingberg, Eva and Bengtsson, Anders and Hansson, Monika and Olsson, Sophie and Pin, Elisa and Klareskog, Lars and Kapetanovic, Meliha C}},
  issn         = {{1873-2518}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{20}},
  pages        = {{3247--3257}},
  publisher    = {{Elsevier}},
  series       = {{Vaccine}},
  title        = {{The impact of immunomodulating treatment on the immunogenicity of COVID-19 vaccines in patients with immune-mediated inflammatory rheumatic diseases compared to healthy controls. A Swedish nationwide study (COVID19-REUMA)}},
  url          = {{http://dx.doi.org/10.1016/j.vaccine.2023.03.065}},
  doi          = {{10.1016/j.vaccine.2023.03.065}},
  volume       = {{41}},
  year         = {{2023}},
}