Effectiveness of SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on DMARDs: as determined by antibody and T cell responses

Abstract

ObjectivesTo assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs).MethodsThis prospective study recruited 100 patients with RA on a variety of DMARDs for antibody and T cell analysis, pre-vaccination and 4 weeks post-vaccination. Positive antibody response was defined as sera IgG binding to ≥1 antigen. Those that remained seronegative after first vaccination were retested 4 weeks after second vaccination; and if still seronegative after vaccination three. A T cell response was defined an ELISpot count of ≥7 interferon (IFN)γ-positive cells when exposed to spike antigens. Type I IFN activity was determined using the luminex multiplex assay IFN score.ResultsAfter vaccine one, in patients without prior SARS-CoV-2 exposure, 37/83 (45%) developed vaccine-specific antibody responses, 44/83 (53%) vaccine-specific T cell responses and 64/83 (77%) developed either antibody or T cell responses. Reduced seroconversion was seen with abatacept, rituximab (RTX) and those on concomitant methotrexate (MTX) compared to 100% for healthy controls (p<0.001). Better seroconversion occurred with anti-tumour necrosis factor (TNF) versus RTX (p=0.012) and with age ≤50 (p=0.012). Pre-vaccine SARS-CoV-2 exposure was associated with higher quantitative seroconversion (≥3 antibodies) (p<0.001). In the subgroup of non-seroconverters, a second vaccination produced seroconversion in 54% (19/35), and after a third in 20% (2/10). IFN score analysis showed no change post-vaccine.ConclusionPatients with RA on DMARDs have reduced vaccine responses, particularly on certain DMARDs, with improvement on subsequent vaccinations but with approximately 10% still seronegative after three doses.

Glucocorticoid use as a cause of non-cellular immune response to SARS-Cov2 Spike in patients with immune system diseases

“…We confirm that T cell response to COVID-19 vaccine is defective among ISD patients receiving DMT as reported in MS and rheumatoid arthritis (RA) [ 22 ]. Anti-CD20 mAb most likely affects the humoral anti-Spike response but has no strong effect on the T cell response [ 22 ]. From our knowledge, our study is the first to incriminate GC as the main DMT to dampen the T cell response against Spike, and such an effect is observed both following COVID-19 vaccine and infection.…”

“…In contrast, T cell responses on GC treated patients have been described only in small cohorts of patients. T cell exploration was limited to ISD patients showing a defective humoral response or after the exclusion of previously SARS-Cov2 infected patients [ 5 , 11 , 21 , 22 ]. We confirm that T cell response to COVID-19 vaccine is defective among ISD patients receiving DMT as reported in MS and rheumatoid arthritis (RA) [ 22 ].…”

“…T cell exploration was limited to ISD patients showing a defective humoral response or after the exclusion of previously SARS-Cov2 infected patients [ 5 , 11 , 21 , 22 ]. We confirm that T cell response to COVID-19 vaccine is defective among ISD patients receiving DMT as reported in MS and rheumatoid arthritis (RA) [ 22 ]. Anti-CD20 mAb most likely affects the humoral anti-Spike response but has no strong effect on the T cell response [ 22 ].…”

Persistence of SARS-CoV-2 neutralizing antibodies and anti-Omicron IgG induced by BNT162b2 mRNA vaccine in patients with autoimmune inflammatory rheumatic disease: an explanatory study in Japan

“… 21 ABT also binds to CD80/86 expressed on B cells and inhibits antibody production, 22 , 23 which means that ABT can affect humoral immune responses both directly and indirectly. These mechanisms may result in the reduced immunogenicity of vaccines such as pneumococcal, 24 influenza, 25 and SARS-CoV-2 mRNA vaccines 26 for patients undergoing treatment with ABT. As previously reported, in our short- and medium-term observations, patients undergoing treatment with ABT had lower adjusted NAb titers than HCs.…”

Postvaccination anti-S IgG levels predict anti-SARS-CoV-2 neutralising activity over 24 weeks in patients with RA

“…While longitudinal studies in SARS-CoV-2 convalescent and vaccinated individuals have revealed the dynamics of humoral and cellular immune responses in healthy individuals, data on long-term vaccine-induced immune responses in patients with rheumatic diseases are still scarce 3–5. Two doses of mRNA-based anti-SARS-CoV-2 vaccines result in durable SARS-CoV-2 antibody binding that correlate to potent neutralisation responses in healthy volunteers 6 7. Most patients with rheumatic diseases seroconvert following mRNA vaccination but anti-S titres may develop with a delayed kinetic and lower magnitude compared with healthy controls (HCs) depending on the immunomodulatory therapies used 8–10…”