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Observational Study
. 2025 Sep 23;15(9):e094948.
doi: 10.1136/bmjopen-2024-094948.

Antibody development after three mRNA SARS-CoV-2 vaccinations in patients with systemic autoimmune rheumatic disease with and without treatment: an observational cohort study

Elisabeth Simader  1 , Felix Kartnig  2 , Selma Tobudic  3 , Daniel Mrak  2 , Thomas Deimel  2 , Thomas Karonitsch  2 , Helmuth Haslacher  4 , Thomas Perkmann  4 , Gregor Mitter  2 , Stefan Winkler  3 , Daniel Aletaha  2 , Stephan Blueml  2 , Peter Mandl  2
Affiliations
Observational Study

Antibody development after three mRNA SARS-CoV-2 vaccinations in patients with systemic autoimmune rheumatic disease with and without treatment: an observational cohort study

Elisabeth Simader et al. BMJ Open. .

Abstract

Objectives and design: To further elucidate the effects of rare systemic autoimmune rheumatic diseases (SARD) and their treatment on antibody development after vaccination against SARS-CoV-2, we compared patients with and without immunosuppressive therapy to healthy controls in an observational cohort study.

Participants and setting: We enrolled 52 patients with SARD and 72 healthy subjects in a prospective, observational study at the Medical University of Vienna and measured the humoral response 6 months after two mRNA vaccinations and 2-6 weeks after a third dose.

Results: Patients with vasculitis showed significantly (p=0.02) lower antibody titres 6 months after vaccination (median 247 BAU/mL, IQR [185-437]), as compared with healthy controls (median 514 BAU/mL, [185-437], IQR 323; 928, vasculitis patients: 247, IQR [185; 437], p<0.05). Patients receiving 2-3 immunomodulatory medications showed significantly lower antibody levels. Of note, all patients with SARD, even those without immunomodulatory medication, developed lower antibody levels after the third dose compared with healthy controls (median 22 630, IQR [16 945; 43 200] in HC, 9510 IQR [3866; 14 215] in patients without immunosuppressive treatment (p<0.001), 7780 IQR [2203; 15 645] in patients receiving a single immunomodulatory drug (p<0.0001) and 14 320 IQR [2415; 35 400] in patients receiving combination therapy (p=0.081)).

Conclusions: Patients with SARD displayed lower antibody development after booster vaccination, even if antibody levels after two immunisations were comparable to healthy controls. Our data may be limited due to sample size, but it provides pointers for a more individualised, antibody-titre-oriented approach and earlier booster vaccination in patients with SARD.

Keywords: COVID-19; Chronic Disease; IMMUNOLOGY; Rheumatology.

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Conflict of interest statement

Competing interests: Prof. PM reports speaker fees from AbbVie, Janssen and Novartis and research grants from AbbVie, BMS, Novartis, Janssen, MSD and UCB; Dr. SB reports personal fees from Abbvie, personal fees from Novartis, outside the submitted work; Prof. HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis; Prof. DA reports grants from Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, other from Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, outside the submitted work; Prof. SB reports personal fees from Abbvie, personal fees from Novartis, outside the submitted work; Dr. ES reports speaker fees from Lilly, MSD and supports for attendance of meetings from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim and Astra Zeneca outside the submitted work; Dr. ST, Dr. DM, Dr. FK, Dr. TD, Mr. GM, Dr. TK, Prof. TP, Prof. SW: nothing to declare.

Figures

Figure 1
Figure 1. SARS-CoV-2 receptor-binding domain (RBD) antibody levels measured 6 months after the second vaccination in healthy controls (HC) and patients with vasculitis or connective tissue disease (CTD).
Figure 2
Figure 2. SARS-CoV-2 receptor-binding domain (RBD) antibody levels measured 6 months after the second vaccination of healthy control subjects (HC); patients receiving no immunosuppressive therapy (none); patients receiving a single conventional systemic disease-modifying drug (csDMARD) or biological or targeted synthetic DMARD b/tsDMARD (mono); and patients receiving combination therapy of csDMARD, b/tsDMARD and/or glucocorticoids (combination).
Figure 3
Figure 3. SARS-CoV-2 receptor-binding domain (RBD) antibody levels measured after the third vaccination in healthy control subjects (HC) and patients with vasculitis or connective tissue disease (CTD).
Figure 4
Figure 4. SARS-CoV-2 receptor-binding domain (RBD) antibody levels measured after the third vaccination of healthy control subjects (HC); patients receiving no immunosuppressive therapy (none); patients receiving a single conventional systemic disease-modifying drug (csDMARD) or biological or targeted synthetic DMARD b/tsDMARD (mono); and patients receiving combination therapy of csDMARD, b/tsDMARD and/or glucocorticoids (combination).
See this image and copyright information in PMC

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