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)

Martina Frodlund¹, Katerina Chatzidionysiou², Anna Södergren³, Eva Klingberg⁴, Anders A Bengtsson⁵, Monika Hansson², Sophie Ohlsson⁶, Elisa Pin⁷, Lars Klareskog⁸ and Meliha Kapetanovic⁹, ¹Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden, ²Department of Medicine, Solna, Division of Rheumatology, Karolinska University Hospital at Karolinska Institutet, Stockholm, Sweden, ³Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden and Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden, ⁴Dept of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, ⁵Department of Clinical Sciences, Lund, Section for Rheumatology, Lund University, Lund and Skåne University Hospital, Lund, Sweden, ⁶Department of Clinical Sciences, Lund, Section for Nephrology, Lund University, Lund and Skåne University Hospital, Lund, Sweden, ⁷Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden, ⁸Karolinska Institutet, Stockholm, Sweden, ⁹Lund University, Department for clinical sciences Lund, section of rheumatology and Lund University Hospital Lund and Malmö, Lund, Sweden

Meeting: ACR Convergence 2022

Keywords: autoimmune diseases, Biologicals, COVID-19, Disease-Modifying Antirheumatic Drugs (Dmards), rheumatoid arthritis

Session Information

Date: Sunday, November 13, 2022

Title: Immunological Complications of Medical Therapy Poster

Session Type: Poster Session B

Session Time: 9:00AM-10:30AM

Background/Purpose: The aim of the study was to elucidate antibody responses after vaccination with two doses of COVID-19 vaccines in patients with inflammatory rheumatic diseases (IRD) treated with biologic and targeted disease modifying anti-rheumatic drugs (b/ts DMARDs) as monotherapy or together with conventional synthetic DMARDs (csDMARDs).

Methods: Antibody levels to antigens representing spike full length protein, spike S1 and a nucleocapsid C-terminal fragment were measured in serum obtained before and 2-12 weeks after second vaccination using multiplex bead-based serology assay. Cut-off for reactivity was defined as mean signal intensity +6SD across 12 pre-pandemic samples for spike and +12SD for nucleocapsid. Patients with IRD receiving b/ts DMARDs and controls from five Swedish regions participated. Percentage (%) responders, defined as antibody levels over cut-off for both spike proteins, in each treatment group was compared to percentage responders among controls. Predictors of antibody response were determined using logistic regression analysis.

Results: In total, 414 patients and 61 controls participated. Of these, 323 had RA/JIA/psoriatic arthritis/spondylarthritis, 60 systemic vasculitis and 31 other autoimmune diseases. The following treatments were studied: rituximab (n=145), abatacept (n=22), IL6-inhibitors (n=79), JAK-inhibitors (n=58), TNF-inhibitors (n=68), IL12/23/IL17-inhibitors (n=42) and healthy individuals (controls; n=61). Patients receiving rituximab (40.7%), abatacept (55.6%), or IL6-inhibitors (87.0 %) had lower antibody response rate compared to controls (98.4%) which was more pronounced when b/ts DMARD was given in combination with csDMARDs (p< 0.001). There was no difference in response between patients receiving IL12/23/IL17-inhibitors, TNF-inhibitors or JAK-inhibitors and controls. Older patients, those receiving concomitant csDMARDs, prednisolone, and with vasculitis had lower proportion of responders (p< 0.0001). After adjustment in regression analysis, higher age, rituximab, shorter time between rituximab course and vaccination, abatacept and concomitant csDMARD remained significant predictors of impaired antibody response. An increased activity in IRD was reported by 14 (3.4%) patients.

Conclusion: In this large Swedish study including IRD, impaired immunogenicity of COVID-19 vaccines was observed in patients receiving rituximab or abatacept. Concomitant csDMARD further decreased this response. Older patients had an impaired antibody vaccine response regardless the immunomodulating treatment. Older patients on rituximab and abatacept should be strongly encouraged and prioritized for booster doses of COVID-19 vaccine.

Figure1A and B. Proportion of participants with positive antibody response in each treatment group (monotherapy and b/ts + csDMARD separately) in 414 patients with IRD and 61 controls

The presence of positive antibody response following two doses of COVID_19 vaccine in relation to time between the last rituximab course and vaccination in 145 patients with IRD treated with rituximab with or without concomitant csDMARD.

Predictors of antibody response to two doses of COVID_19 vaccine, defined as antibodies over the cut-off level for both spike antigens in 414 patients with IRD and 61 healthy individuals

Disclosures: M. Frodlund, None; K. Chatzidionysiou, AbbVie/Abbott, Eli Lilly, Pfizer; A. Södergren, None; E. Klingberg, Lilly, UCB Pharma, Roche; A. Bengtsson, None; M. Hansson, None; S. Ohlsson, None; E. Pin, None; L. Klareskog, None; M. Kapetanovic, None.

To cite this abstract in AMA style:

Frodlund M, Chatzidionysiou K, Södergren A, Klingberg E, Bengtsson A, Hansson M, Ohlsson S, Pin E, Klareskog L, Kapetanovic M. 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) [abstract]. Arthritis Rheumatol. 2022; 74 (suppl 9). https://acrabstracts.org/abstract/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/. Accessed .

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