DMARD Combinations Have Deleterious Effects on Immunogenicity of COVID-19 Vaccine in RA

Patients with rheumatoid arthritis (RA) were found to have a moderate response to the inactivated SARS-CoV-2 vaccine Sinovac-CoronaVac, with nearly all disease-modifying antirheumatic drug (DMARD) combinations conferring a deleterious effect on immunogenicity of the vaccine, according to study results published in Annals of the Rheumatic Diseases.

A subanalysis of the prospective, single-center, controlled, phase 4 CoronavRheum study (ClinicalTrials.gov Identifier: NCT04754698) was conducted that evaluated the immunogenicity and safety of the CoronaVac vaccine in patients with autoimmune rheumatic diseases. The aim of the current study was to assess the impact of DMARD combinations and monotherapy on immune response to the COVID-19 vaccine in RA.

Researchers analyzed seroconversion of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralizing antibodies (NAbs) induced by the COVID-19 vaccine among individuals in the RA group compared with those in the control group. Disease activity and treatment were also evaluated. Participants with baseline-negative IgG/NAbs were eligible for study inclusion.

Study participants were followed-up with regularly at the Outpatient Clinics of Rheumatology Division (Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Brazil). The cohort included a total of 260 participants (mean age, 59 years) in the RA group and 104 individuals (mean age, 58 years) in the control group.

Patients with RA vs control participants had moderate but significantly lower seroconversion (61.8% vs 94.2%, respectively; P <.001) and NAb positivity (45.0% vs 78.6%, respectively; P <.001), following full vaccination. Immunogenicity was not affected by baseline disease activity.

Based on multivariate analyses, factors independently associated with reduced seroconversion included older age for each 5-year interval (odds ratio [OR], 0.79; 95% CI, 0.70-0.89; P <.001); methotrexate (MTX) use (OR, 0.54; 95% CI, 0.29-0.98; P =.044); abatacept therapy (OR, 0.37; 95% CI, 0.19-0.73; P =.004); and number of DMARDs used (OR, 0.55; 95% CI, 0.33-0.90; P =.018).

With regard to NAbs, age for each 5-year interval (OR, 0.87; 95% CI, 0.78-0.96;

P =.007) and a prednisone dose of greater than 7.5 mg/day (OR, 0.38; 95% CI, 0.19-0.74; P =.004) were both negatively associated with the presence of NAbs.

Additional analysis of seroconversion/NAb positivity in the RA and control groups showed that MTX/tofacitinib/abatacept/tocilizumab use, as monotherapy or combination therapy, was associated with lower responses (P <.05), whereas tumor necrosis factor (TNF) inhibitor and other conventional synthetic DMARDs exhibited deleterious effects when used in combination with other treatments.

Study limitations included the lack of assessing Disease Activity Scores with 28 joints (DAS28) after immunization, as well as T-cell responses, and the small sample size of control participants.

The researchers concluded, “…these findings reinforce the need of a broader approach, not limited to a specific drug temporary suspension, to improve vaccine response for this population.”

Reference

Medeiros-Ribeiro AC, Bonfiglioli KR, Domiciano DS, et al. Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis. Ann Rheum Dis. Published online February 8, 2022. doi:10.1136/annrheumdis-2021-221735