Interaction of TNFi and conventional synthetic DMARD in SARS-CoV-2 vaccine response in axial spondyloarthritis and psoriatic arthritis

Joint Bone Spine. 2023 Jan;90(1):105464. doi: 10.1016/j.jbspin.2022.105464. Epub 2022 Sep 20.


Objectives: To evaluate humoral responses to three doses of the inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with spondyloarthritis (SpA) and the effect of therapy, compared with a control group (CG).

Methods: Prospective cohort of axial SpA/psoriatic arthritis patients and age/sex-balanced CG from the CoronavRheum phase 4 trial (NCT04754698). CoronaVac was given in two doses (28-days interval) with a booster at day 210. Blood samples were collected in the days 0/28 (D28)/69 (D69) and 240 (D240) to evaluate anti-SARS-CoV-2 IgG seropositivity (SP) and neutralising antibodies (NAb).

Results: One hundred and ninety-four SpA patients were enrolled and 183 patients were age/sex-balanced with 183 CG. At D69, SpA patients showed a high SP (80.2% vs. 95.7%, P<0.001) and moderate NAb positivity (61.6% vs. 82.7%, P<0.001), but lower than CG. In patients, older age prednisone (P<0.001), methotrexate (MTX) (P<0.001) and TNF inhibitors (TNFi) (P<0.001) were independently associated with lower SP, while Caucasian ethnicity (P<0.05) and prednisone (P<0.01) were associated with diminished NAb. In contrast, sulfasalazine (SSZ) use was associated with NAb presence (P<0.05). In monotherapy, only TNFi was also associated with absence of SP (P<0.05). Further comparison with CG revealed that TNFi and/or MTX negatively impacted SP/NAb (P<0.05). In contrast, patients under SSZ monotherapy achieved 100% SP (P>0.999) and 83.3% NAb positivity (P>0.999). SSZ+TNFi combination resulted in a similar response than CG [SP (P=0.153) and NAb (P=0.715)]. After third dose (D69-D240), a major increment occurred for SP (81.3% to 93.1%, P<0.001) and NAb (63.2% to 86.1%, P<0.001), but still lower than CG (P<0.05), and only TNFi impaired both SP (P=0.016)/NAb (P=0.002).

Conclusions: We provided novel data demonstrating that TNFi attenuates immunogenicity in SpA patients while SSZ has a positive impact on vaccine antibody production. We also confirmed that MTX in combination with TNFi had a major negative impact in vaccine humoral response (CoronavRheum #NCT04754698).

Keywords: Ankylosing spondylitis; COVID-19; Psoriatic arthritis; Therapeutics and TNFi; Vaccination.

Publication types

  • Clinical Trial, Phase IV

MeSH terms

  • Antirheumatic Agents* / therapeutic use
  • Arthritis, Psoriatic* / drug therapy
  • Axial Spondyloarthritis*
  • COVID-19 Vaccines / therapeutic use
  • COVID-19*
  • Female
  • Humans
  • Male
  • Methotrexate / therapeutic use
  • Prednisone / therapeutic use
  • Prospective Studies
  • SARS-CoV-2
  • Spondylarthritis* / drug therapy
  • Sulfasalazine / therapeutic use
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use
  • Tumor Necrosis Factor-alpha / therapeutic use


  • Antirheumatic Agents
  • COVID-19 Vaccines
  • Methotrexate
  • Prednisone
  • sinovac COVID-19 vaccine
  • Sulfasalazine
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factor-alpha

Associated data