ABSTRACT
Patients with inflammatory rheumatic diseases (IRD) have an increased risk for a worse COVID-19 outcome, and impaired immune responses following mRNA COVID-19 vaccines have been observed. In this prospective observational study, we compared the anti-S1 response following vaccination with BNT162b2 and mRNA- 1273 in a large cohort of IRD patients and assessed the effect of different immunomodulatory treatments. Patients from SCQM, the Swiss IRD cohort, who assented to an mRNA COVID-19 vaccine were recruited into the study between 3/2021-9/2021. Participants answered the study questionnaire via the mySCQM patient app and provided self-collected capillary blood samples at baseline, 4, 12, and 24 weeks post second vaccine dose. Samples were tested for IgG antibodies against the S1 domain of the SARS-CoV-2 spike protein using the EUROIMMUN ELISA. We examined differences in antibody titres depending on the vaccine and treatment received, while adjusting for age and history of SARSCoV- 2 infection, by applying mixed effects continuous outcome logistic regression models at each timepoint. Eligible samples were obtained from 564 IRD patients (mean age 53 y (s.d. 12 y), 66% female) with 36% RA, 37%, axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARD & no steroids 15%), csDMARD (9%), TNFi (48%), IL-6/17/23i (14%), JAKi (6%), rituximab (4%), abatacept (3%), and PDE4i (1%) in mono/combination therapy at baseline. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. Independently of the disease, treatment, and history of SARS-CoV- 2 infection, the odds of having higher anti-S1 titres at 4, 12, and 24 weeks post second vaccine dose were, respectively, 3.3, 3.9, and 3.8 times higher with mRNA-1273 compared to BNT162b2 for the average-aged patient of this population (p <0.0001). Moreover, with every year of age, the odds of higher anti-S1 levels increased by 3% to 5% following mRNA-1273 vs BNT162b2 vaccination (p <0.05), indicating an additional benefit for elderly IRD patients. Among monotherapies, rituximab, abatacept, JAKi, and TNFi had the highest odds of reduced anti-S1 responses compared to no medication. Patients on specific combination therapies showed significantly reduced antibody responses compared to respective monotherapies. Our results suggest that in IRD patients, vaccination with mRNA- 1273 vs BNT162b2 results in higher anti-S1 antibody titres, and has an additional benefit in elderly patients.
ABSTRACT
Background: Patients on immunomodulatory treatments mount an attenuated immune response following mRNA COVID-19 vaccination, yet longterm studies of vaccine-induced anti-SARS-CoV-2 antibody (Ab) kinetics are missing. Objectives: In this prospective observational study, we mapped the humoral antibody response to mRNA COVID-19 vaccines up to 24 weeks post full vaccination in patients with infammatory rheumatic diseases (IRDs). We aimed to assess differences due to treatment, age, past SARS-CoV-2 infection, and vaccine (BNT162b2 vs. mRNA-1273). Methods: Adult patients from the SCQM cohort who assented to an mRNA COVID-19 vaccine were recruited between 3/21-9/21. Participants answered questionnaires via an app and received kits for the self-collection of capillary blood samples at baseline, 4, 12, and 24 weeks post full vaccination. Samples were tested for IgG Ab against the S1 domain of the SARS-CoV-2 spike protein (anti-S1-IgG) using the EUROIMMUN ELISA. To examine differences in Ab titres arising from the defned parameters, while accounting for inter-assay variability, mixed effects continuous outcome logistic regression models were applied at each timepoint. Results: Samples were obtained from 570 patients: 67% female, mean age 53 y (SD 12 y) with 37% RA, 36% axSpA, 21% PsA, and 6% UA (undifferentiated arthritis), on no medication (no DMARDs & no glucocorticoids;15%), csD-MARDs (10%), TNFi (48%), IL-1/6/17/23i (14%), JAKi (6%), rituximab (RTX;4%), or abatacept (ABA;2%) in mono/combination therapy at the frst vaccination. 10% of patients had a past SARS-CoV-2 infection, 54% received BNT162b2, 46% mRNA-1273. For any Ab threshold, the odds of having a higher Ab titre at 4, 12, and 24 weeks post full vaccination were 3.3-4 times higher with mRNA-1273 compared to BNT162b2 (Table 1, Figure 1). TNFi, JAKi, RTX, and ABA as monotherapy resulted in signifcantly lower Ab levels compared to no medication at almost all timepoints. In combination therapy, TNFi, IL-1/6/17/23i, RTX, and csDMARDs led to consistently lower Ab titres at all timepoints compared to respective monotherapy. Conclusion: Compared to no medication, some immunomodulatory therapies resulted in markedly lower Ab levels at all timepoints. In IRD patients, a past SARS-CoV-2 infection resulted in strikingly increased immunogenicity, as did mRNA-1273 compared to BNT162b2.