Humoral and cellular SARS-CoV-2 vaccine responses in patients with giant cell arteritis and polymyalgia rheumatica

Abstract

ObjectivesGiant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinflammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, methotrexate, leflunomide and tocilizumab. In this study, we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases (based on humoral and cellular immunity).MethodsPatients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks after the second dose (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-vaccination and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared with age-, sex- and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specific T-cells was assessed by IFN-γ ELIspot assay, and side effects and disease activity were recorded.ResultsGCA/PMR patients did not have reduced antibody concentrations compared with controls. However, linear regression analysis revealed a significant association of methotrexate and >10 mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients. Patients using >10 mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to significant side effects or changes in disease activity.ConclusionsSARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10 mg/day prednisolone did show lower vaccine responses, which corroborates findings in other autoinflammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection.

Humoral SARS–CoV‐2 Vaccine Responses in Patients With Giant Cell Arteritis and Polymyalgia Rheumatica: Decay After Primary Vaccination and Effects of the Booster

“…A possible explanation for the accelerated waning may be that prednisolone impairs the antigen presentation and germinal center reactions that are required for long-lasting immune responses, whereas methotrexate has more effect on B cells only. This is supported by the findings in our primary study, which showed impaired cellular immunity in GCA/PMR patients taking ≥10 mg/day of prednisolone, but not in those taking methotrexate (6).…”

“…EULAR guidelines have named prednisolone and methotrexate among the few immunosuppressive drugs that likely impact vaccine immunogenicity. Our previous study in GCA and PMR patients, in congruence with further studies in these patients, highlighted that methotrexate and higher dosages of prednisolone associated with hampered humoral vaccine responses (4)(5)(6), and in patients using >10 mg/day prednisolone, also cellular immunity was impaired.…”

“…In this study, we show that antibody concentrations postprimary vaccination strongly associate with post-booster concentrations. As impaired primary vaccine responses were linked to high-dose prednisolone or methotrexate treatment (5,6), this implies that humoral immunity post booster is affected by medication use during the primary vaccination. However, prednisolone or methotrexate use did not impact the immunogenicity of the booster vaccines, as fold changes in antibodies were not associated with treatment in the linear regression analysis.…”

“…Patients and controls. This study follows patients who were included in our primary vaccination study (6) (see Supplementary Figure 1, available on the Arthritis Care & Research website at http://onlinelibrary.wiley.com/doi/10.1002/acr.25173, for a patient flow chart). Participants in the primary study were recruited from the longitudinal GPS (GCA, PMR, SENEX) cohort.…”

“…Antibody responses. Antibodies against the Spike protein S1 and nucleocapsid protein of SARS-CoV-2 were assessed using the same multiplex bead-based Immuno assay as the primary vaccination study and expressed in binding antibody units (BAU) (6,8). Patients and controls who showed a strong increase in antinucleocapsid antibodies during follow-up and those who had reported a positive SARS-CoV-2 test were considered infected.…”