Immunogenicity, Safety, and Clinical Outcomes Following Homologous and Heterologous SARS-CoV-2 Vaccination Regimens in Patients with Axial Spondyloarthritis and Psoriatic Arthritis: A Prospective Observational Study from the SAFER Cohort

Background/Objectives: Patients with spondyloarthritis (SpA) frequently receive immunomodulatory therapies that may influence vaccine-induced immune responses. However, evidence comparing the immunogenicity, safety, and clinical outcomes following homologous and heterologous SARS-CoV-2 vaccination regimens in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) remains limited. Methods: This observational study was conducted within the Brazilian multicenter SAFER cohort and included adults with axSpA or PsA who received three doses of SARS-CoV-2 vaccines through the Brazilian National Immunization Program. The primary outcome was humoral immunogenicity, assessed by anti-receptor-binding domain (anti-RBD) IgG geometric mean titers (GMTs). Clinical outcomes, disease activity, and safety were evaluated throughout follow-up. Results: Ninety patients (axSpA = 69; PsA = 21) were included. Antibody titers increased progressively after vaccination, with GMTs rising from 6.70 BAU/mL at baseline to 907.72 BAU/mL after the additional dose. Humoral responses were comparable between axSpA and PsA throughout follow-up. Participants with previous SARS-CoV-2 exposure consistently exhibited higher antibody responses than infection-naïve individuals. Although ChAdOx1-S elicited stronger early humoral responses than CoronaVac, heterologous regimens incorporating a BNT162b2 additional dose produced the highest post-additional-dose antibody concentrations. Serological response rates reached 100% after the additional dose, irrespective of disease subtype or vaccination regimen. Biologic disease-modifying antirheumatic drugs (bDMARDs), including TNF inhibitors, were not significantly associated with reduced antibody responses. Only four COVID-19 cases occurred during follow-up, with no hospitalizations or deaths. Disease activity remained stable, and adverse events were predominantly mild and self-limited. Conclusions: SARS-CoV-2 vaccination was safe and highly immunogenic in patients with axSpA and PsA, without compromising disease activity control. Heterologous vaccination regimens incorporating a BNT162b2 additional dose elicited the strongest humoral immune responses. These findings provide prospective real-world evidence supporting optimized additional-dose strategies and may inform future vaccination approaches for patients with SpA.