DETECTION of SARS COV-2 ANTIBODIES FOLLOWING VACCINATION in PATIENTS with RHEUMATIC MUSCULOSKELETAL DISEASE (DECODIR)-AN INTERIM REPORT from A DANISH PROSPECTIVE COHORT STUDY

ABSTRACT

Background: During the COVID-19 pandemic, it remains a major concern whether patients with rheumatic musculoskeletal disease treated with conventional (cs) or biologic (b) disease modifying drugs (DMARDs) exhibit an adequate immune response to the currently available SARS-CoV2 vaccines. There remains an urgent need for more data on SARS-CoV-2 vaccine efficacy to inform healthcare providers on the efficiency of the applied vaccination, potential need of and period for booster and/or re-vaccination. Objectives: To assess and compare the efficacy of the SARS-CoV2 vaccines BNT162b2 vaccine (Pfzer/BioNTech) and mRNA-1273 vaccine (Moderna). (The vaccines were administered as part of the Danish vaccine roll out and offered each with two doses and approximately four weeks apart). Patients' SARS-CoV2 IgG serum level was used as proxy to determine vaccination response. Methods: We established the 'Detection of SARS-CoV2 antibodies in Danish Infammatory Rheumatic Outpatients' study (DECODIR) as a longitudinal prospective cohort study. Patients with rheumatoid arthritis (RA), spondyloarthrop-athies (SpA) or psoriatic arthritis (PsA) receiving their outpatient treatment and monitored in the Danish DANBIO registry at the Danish Hospital for Rheumatic Diseases (DG), Sonderborg were included (April-June 2021). Bloods, patient reported outcome measurements (PROMS), clinical data and treatment information (cs/bDMARD) were collected at baseline (prior to vaccination) and after six weeks and six months. SARS-CoV2 IgG levels in serum were assessed by ELISA (ThermoFischer), and manufacturer's cut-off (>=10 EliA U/mL) selected as defnition of sufficient IgG response. Associations between antibody response, age, gender, disease (RA/PsA/SpA), treatment with no or cs/bDMARDs and disease activity were tested using proportional odds regression and bootstrapped tests of medians. Results were reported using mean, median (IqR) and bootstrapped 95% confdence interval (CI) of the median. Results: A total of 243 patients were included at baseline and after six weeks;at six months' follow-up data were available for 233 patients. After six weeks, vaccination was followed by a signifcant increase in IgG levels (median of <0.7 EliA U/mL at baseline versus 36.5 EliA U/mL). Patients treated with a combination of both cDMARD and bDMARD had signifcantly lower IgG levels compared to patients without any DMARD treatment (8,2 EliA U/mL vs 19.5 EliA U/mL (p<0.001)). Patients treated with oral prednisolone (any dose) also showed signifcantly lower median IgG levels compared to patients without DMARD treatment (3,8 EliA U/mL vs 19.5 EliA U/mL (p<0.01)). The actual measurements six months after baseline demonstrated a signifcant decrease of IgG levels for the whole study population (median of 16 EliA U/mL at six month vs 36.5 EliA U/mL at six weeks, p < 0.001) (Figure 1). Similar to week 6, lowest response rates were found in patients treated with prednisolone or combination of csDMARD and bDMARD. After 6 months, the proportional odds model revealed signifcantly lower median IgG antibody level in patients who received Pfzer compared to Moderna (median 15 EliA U/mL (95%CI 13-18) vs 44.5 EliA U/mL (95%CI 36-83) (p<0.001). Conclusion: IgG levels decreased markedly six months after the initial double dose regimen. Patients treated with a combination of cs/bDMARD or oral pred-nisolone are at higher risk of inadequate vaccine response as measured by IgG level. Our results support the decision for the need of a third booster vaccine in patients with infammatory rheumatic diseases, especially in the case of cs/bDMARD combination treatment and prednisolone. The data may indicate a need for further revaccination in these patients.