Effect of Therapy on COVID-19 Vaccine Response Studied Among Patients With Spondyloarthritis

Close-up of a doctor applying the covid-19 vaccine to a senior patient at nursing home during the isolation. Healthcare and medicine concept.
Researchers studied humoral responses to 3 doses of the COVID-19 vaccine, as well as the effect of therapy, among patients with spondyloarthritis.

Treatment of spondyloarthritis (SpA) with tumor necrosis factor inhibitors (TNFis), especially in combination with methotrexate (MTX), was found to suppress humoral response after 3 COVID-19 vaccine doses; however, sulfasalazine was shown to improve vaccine antibody production, according to study findings published in Joint Bone Spine.

Researchers analyzed a phase 4, single-center, prospective, observational cohort study (CoronavRheum; ClinicalTrials.gov Identifier: NCT04754698) in Brazil to determine the effect of therapy on humoral responses following 3 COVID-19 vaccination doses in patients with SpA compared with healthy control participants.

Researchers collected demographic and current treatment regimen information for SpA, including prednisone, MTX, sulfasalazine, and TNFis, as well as any combination of these medications.

All participants received 2 doses of the COVID-19 vaccine at day 0 and day 28, with a booster dose on day 210.

Patients provided blood samples at baseline prior to COVID-19 vaccination and at days 28 and 240 to measure neutralizing antibody levels and immunoglobulin G (IgG) seropositivity against SARS-CoV-2.

A total of 194 patients with SpA and 183 age- and sex-matched control participants were included in the analysis.

Researchers observed that IgG seropositivity in patients with SpA peaked around day 69, with a moderate positivity for neutralizing antibodies. Significantly fewer patients with SpA vs control participants achieved higher levels of seropositivity (80.2% vs 95.7%, respectively; P <.001) and neutralizing antibodies (61.6% vs 82.7%, respectively; P <.001).

In patients with SpA, lower seropositivity against COVID-19 correlated with older age (odds ratio [OR], 0.80; 95% CI, 0.65-0.99; P <.05) and treatments such as MTX (OR, 0.06; 95% CI, 0.01-0.26; P <.001), prednisone (OR, 0.06; 95% CI, 0.01-0.29; P <.001), and TNFis (OR, 0.05; 95% CI, 0.01-0.25; P <.001). The TNFis used as a monotherapy also correlated with an absence of IgG seropositivity (OR, 0.21; 95% CI, 0.05-0.90; P <.05).

Lower neutralizing antibody production correlated with prednisone use (OR, 0.19; 95% CI, 0.06-0.65; P <.01) and being White (OR, 0.49; 95% CI, 0.24-0.99; P <.05), while use of sulfasalazine increased neutralizing antibodies (OR, 2.86; 95% CI, 1.04-7.86; P <.05). All patients with SpA receiving treatment with sulfasalazine achieved maximum seropositivity, and 83.3% achieved positivity for neutralizing antibodies (P >.999).

Following the booster dose, seropositivity among patients with SpA increased from 81.3% to 93.1% (P <.001), while neutralizing antibodies increased from 63.2% to 86.1% (P <.001). However, in patients with SpA, the TNFis continued to suppress IgG seropositivity (OR, 0.14; 95% CI, 0.03-0.70; P <.05) and neutralizing antibody response (OR, 0.08; 95% CI, 0.02-0.40; P <.01) after the COVID-19 booster dose.

Study limitations included lack of assessment of cellular immunity and lack of prospective measurement of disease activity.

“We provided novel data demonstrating that TNFi attenuates immunogenicity in SpA patients while [sulfasalazine] has a positive impact on vaccine antibody production,” the study authors said. “We also confirmed that MTX in combination with TNFi had a major negative impact in vaccine humoral response.”


Saad CG, Silva MS, Sampaio-Barros PD, et al. Interaction of TNFi and conventional synthetic DMARD in SARS-COV-2 vaccine response in axial spondyloarthritis and psoriatic arthritis. Joint Bone Spine. Published online September 20, 2022. doi:10.1016/j.jbspin.2022.105464