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

OBJECTIVES: To assess antibody and T cell responses to SARS-CoV-2 vaccination in patients with rheumatoid arthritis (RA) on disease-modifying antirheumatic drugs (DMARDs). METHODS: This 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. RESULTS: After 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. CONCLUSION: Patients 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.

Third-Generation Anti-Cyclic Citrullinated Peptide Antibodies Improve Prediction of Clinical Arthritis in Individuals at Risk of Rheumatoid Arthritis.

OBJECTIVE: To 1) determine the prevalence of anti-cyclic citrullinated peptide 3 (anti-CCP3) antibodies in anti-CCP2 antibody-positive (anti-CCP2+) at-risk individuals, and 2) explore the additional value of anti-CCP3 antibodies in anti-CCP2+ at-risk individuals for predicting progression to inflammatory arthritis. METHODS: Stored serum samples obtained from 347 anti-CCP2+ (BioPlex 2200; Bio-Rad) at-risk individuals without clinical synovitis were tested for anti-CCP3 antibodies. Anti-CCP2 titers were categorized as low or high, and anti-CCP3 titers were categorized as negative, low, or strong. Progression to inflammatory arthritis was defined as the development of clinical synovitis in ≥1 joint. Only subjects with ≥1 follow-up visit were included in the progression analysis (n = 291). RESULTS: In the 347 samples included, anti-CCP3 antibody titers tended to be either negative (n = 138 [39.7%]) or strongly positive (n =189 [54.4%]), with very few subjects showing a low titer (n = 20 [5.7%]). In contrast, for anti-CCP2 antibodies, more low titers were observed (n = 103 [29.7%]). Eighty-eight of 291 subjects (30.2%) developed inflammatory arthritis. The rate of progression to inflammatory arthritis in the low-titer anti-CCP2 group and the high-titer anti-CCP2 group fell from 7.5% to 3.3% and from 38.9% to 9.8%, respectively, when anti-CCP3 was negative. Progression in the high-titer anti-CCP2 group increased from 38.9% to 48.4% when anti-CCP3 was strongly positive. The area under the curve was 0.72 for anti-CCP2 (95% confidence interval [95% CI] 0.66, 0.78) and 0.76 for anti-CCP3 (95% CI 0.70, 0.81) for assessment of progression. In the multivariable analysis, the odds ratio for the development of inflammatory arthritis in anti-CCP3+ subjects was 1.73 (95% CI 1.20, 2.51) (P < 0.01). CONCLUSION: Anti-CCP3 antibodies improve the prediction of inflammatory arthritis in anti-CCP2+ at-risk individuals. The impact of anti-CCP3 antibody status for the risk stratification of individuals with high-titer anti-CCP2 is particularly notable.