PAUSING METHOTREXATE IMPROVES IMMUNOGENICITY of COVID-19 VACCINATION in PATIENTS with RHEUMATIC DISEASES

ABSTRACT

Background: Several research groups have recently described a reduced vaccination response to COVID-19 vaccination under methotrexate (MTX) (1,2). The increase in humoral immune response when pausing MTX two weeks after vaccination has already been described for infuenza vaccination (3). However, data regarding MTX-hold during COVID-19 vaccination are still lacking. Objectives: To study the effect of MTX and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). Methods: In this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 rheumatic patients on methotrexate therapy, 31 of whom temporarily paused medication without a fxed regimen. The control group consisted of 21 AIRD patients without immunosuppressive medication. Results: MTX patients showed a signifcantly lower mean antibody response compared to AIRD patients without immunosuppressive therapy (71.8 % vs 92.4 %, p<0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49;p<0.001). All nine patients with antibody levels below the cutoff were older than 60 years. Patients who held MTX during at least one vaccination showed signifcantly higher mean neutralising antibody levels after second vaccination, compared to patients who continued MTX therapy during both vaccinations (83.1 % vs 61.2 %, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8 % vs 51.9 %, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days. Conclusion: MTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination signifcantly improves the antibody response in patients over 60 years of age.