Intake of Acetaminophen suppresses antiviral humoral immune responses in patients with RA following vaccination with anti SARS-CoV-2 mRNA based vaccines

Background Acetaminophen (APAP = paracetamol) may potentially impact vaccine-associated immune responses as the intake of APAP has been associated with a worse outcome in tumor patients receiving checkpoint inhibitors. [1] Different DMARD regimen have been shown to impair the humoral immune response to mRNA SARS-CoV-2 vaccines in patients with rheumatoid arthritis but the effect of paracetamol has not been explored thus far. Objectives To analyse whether the intake of APAP may interfere with antiviral humoral immune responses following two doses of an anti-SARS-CoV-2 mRNA based vaccine in patients with rheumatoid arthritis (RA) on DMARD therapy. Methods The RECOVER trial ( R heumatoid C ovid-19 V accin e Immune R esponse) was a non-randomised, prospective observational control group trial and enrolled 77 RA patients on DMARD therapy and 21 healthy controls (HC). We performed a posthoc analysis of blood samples taken before the first vaccine dose (T0), two (T1) and three (T2) weeks after the first and second vaccine dose, and at 12 (T3) weeks. APAP intake was measured using ELISA. The antibody response (anti-S) to the receptor binding domain (RBD) within the SARS-CoV-2 S1 protein was measured with the Elecsys Anti-SARS-CoV-2-S (Roche Diagnostics GmbH) test. The neutralizing activity NT50 at week 12 was assessed using an HIV-based pseudovirus neutralization assay against Wuhan-Hu-1. Results Baseline characteristics of participants are detailed in Table 1. The immunogenicity analyses were based on 73 RA patients after exclusion of 4 patients with previously unnoticed SARS-CoV-2 infection (positive for anti-nucleoprotein at baseline). APAP was detected in serum samples from 34/73 (25%) RA patients and in 7/21 (33%) HC (least at one timepoint T0, T1 and/or T2). APAP intake in HC did not affect levels of anti-S at any timepoint and all HC developed potent neutralizing activity (NT50 ≥ 250) at week 12. RA patients, who tested positive for APAP at T1, showed comparable anti-S levels at T1, T2 and T3 compared to RA patients not exposed to APAP. The detection of APAP at T2 corresponded to lower anti-S levels at T2 (Figure 1 A, B). The detection of APAP at T2 was associated with a significantly lower SARS-CoV-2 neutralizing activity at week 12 compared to patients without perivaccination APAP exposure (p =0.04) (Figure 1 C). Conclusion A decrease of antiviral humoral immune responses was observed in RA patients (but not in HC) who were exposed to APAP at the time of the second mRNA vaccine dose compared to patients in whom APAP was not detected. Our data suggest that the use of paracetamol within the time period around vaccination may impair vaccine-induced immune responses in patients with an already higher risk for blunted immune responses. Reference [1]Bessede A et al. Ann Oncol 2022; 33: 909-915 Table 1. Baseline characteristics: RA patients and HC with/without APAP exposure RA APAP – n = 37 RA APAP + n = 36 p-value HC APAP – n = 8 HC APAP + n = 13 p-value Age (yrs), mean (± SD) 62 (13) 67 (10) 0.07 (NS) 45 (12) 44 (14) 0.90 (NS) Female sex, n (%) 24 (65) 19 (53) 0.29 (NS) 2 (25) 5 (38) 0.53 (NS) Vaccination type/schedule mRNA-1273, n (%) 4 (11) 8 (22.2) 0.19 (NS) 0 (0) 0 (0) BNT162b2, n (%) 33 (89) 28 (77.8) 0.19 (NS) 8 (100) 13 (100) RA disease characteristics ACPA ± RF, n (%) 17/37 (46) 19/36 (53) 0.56 (NS) NA NA NA RA disease duration (yrs ± SD) 9.2 (9.8) 10.2 (8.1) 0.67 (NS) NA NA NA DMARD therapy csDMARD-mono, n (%) 13/37 (35) 9/36 (25) 0.35 (NS) NA NA NA bDMARD-mono/combo, n (%) 16/37 (43) 16/36 (44) 0.92 (NS) NA NA NA tsDMARDs-mono/combo, n (%) 8/37 (22) 11/36 (31) 0.38 (NS) NA NA NA Prednisone, n (%) 15/37 (41) 12/36 (33.3) 0.52 (NS) NA NA NA Mean daily dose prednisone (mg ± SD) 4.6 ± 1.1 3.9 ± 2.3 0.39 (NS) NA NA NA * APAP = acetaminophen Figure 1. Acknowledgements: NIL. Disclosure of Interests None Declared.