Inflammatory Rheumatic Disease Linked to Reduced mRNA COVID-19 Vaccine Response

Catherine Raptis, PhD

Spike protein antibody response in persons vaccinated with mRNA COVID-19 vaccines is significantly reduced among patients with inflammatory rheumatic disease and varying regimens of immunomodulating therapy.

In late-breaking data presented at the American College of Rheumatology (ACR) 2021 Convergence Tuesday, a team of Switzerland investigators observed stark contrasts in COVID-19 mRNA vaccination response among inflammatory rheumatic disease patients and the general population—yet similarities in vaccine response among those previously infected with SARS-CoV-2.

Led by Catherine Raptis, PhD, Deputy Head of Science at the SCQM Foundation, investigators sought to longitudinally map the anti-Spike protein response to mRNA COVID-19 vaccines in patients with inflammatory rheumatic diseases (IRDs) on differing regimens through 24 weeks post-full vaccination.

“Emerging evidence indicates that immunosuppressive therapies may result in reduced immunogenicity—and presumably reduced efficacy—following vaccination with mRNA COVID-19 vaccines but long-term data is missing,” Raptis and colleagues wrote.

Their cohort included adult patients from SCQM, a Swiss long-term observational registry for patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis. Eligible patients were willing to receive a COVID-19 mRNA vaccine and participate in an observational follow-up trial that included mobile app-based questionnaires and self-collected capillary blood drawings from finger pricks.

Investigators collected blood samples at baseline, weeks 4, 12, and 24 post-full vaccination. They were tested for immunoglobulin G (IgG) antibodies against the S1 domain of the SARS-CoV-2 spike protein, via an ELISA kit.

A total of 912 patients were recruited since March 2021; through August, 441 had provided eligible serum samples at baseline, then weeks 4 and 12 post-full vaccination.

Raptis and colleagues observed an association between tumor necrosis factor (TNF) inhibitor and decreased anti-S1 immune response in SARS-CoV-2 naïve patients with IRD, compared to non-disease modifying antirheumatic drug (DMARD) regimens, at both weeks 4 and 12. The association was noted in both monotherapy and combination therapy regimens, but was more significant in the latter.

Investigators additionally noted rituximab significantly affected anti-S1 response versus non-DMARD therapy at both weeks 4 and 12; 4 of the 11 observed rituximab-treated patients failed to seroconvert after full mRNA COVID-19 vaccination.

Peak response and diminished decline in anti-S1 antibodies were significantly higher from 4 to 12 weeks post-vaccination in patients who recovered from previous SARS-CoV-2 infection versus naïve patients.

The preliminary assessment results demonstrated significantly reduced spike protein antibody response and kinetics in fully COVID-19 vaccinated patients with IRD. Reduced response varied by rheumatic therapy. Though the trial was limited by a lack of comparative health controls and data related to cellular immune response derived from vaccination, the findings contribute to the understood risk of reduced mRNA vaccine response in patients with rheumatic disease.

“Further analysis will allow to assess the anti-S1 response at 24 weeks post full vaccination, with more covariates, including, treatment changes around the time of vaccination, age, and vaccine received,” the team concluded.

The study, “Immunogenicity of mRNA COVID-19 Vaccines at 4 and 12 Weeks Post Full Vaccination in Patients with Inflammatory Rheumatic Diseases,” was presented at ACR 2021.