Eficácia e segurança da vacinação antiamarílica em pacientes com espondiloartrite

• Ano de defesa: 2021
• Autor(a) principal: Casagrande, Thays Zanon
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Mestrado em Saúde Coletiva; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Saúde Coletiva
• Palavras-chave em Português: Febre amarela; vacina 17DD-YF; vacina antiamarílica; espondiloartrites; terapia biológica; biomarcadores séricos; quimiocinas; citocinas; subject.br-rjbn; Saúde Coletiva
• Link de acesso: http://repositorio.ufes.br/handle/10/15069

Background: Yellow Fever (YF) vaccination might cause many adverse events (AE) and suboptimal responses in patients with autoimmune diseases (AID); however, there have been no studies on 17DD-YF primary vaccination performance in spondyloarthritis group. Those patients are younger and have less comorbidities than other AID patients and frequently receive biological therapy, which is known to reduce immune response. In 2017, the Brazil yellow fever epidemic triggered the need to vaccinate most people and made this study an opportunity. Objective: This study aimed to assess safety and efficacy of 17DD-YF primary vaccination in spondyloarthritis patients, and to assess whether disease activity or prior biological therapy, even after planned washout, impact overall performance of immune response. Methods: Prospective non-interventional study accomplished in 2017 assessing safety and immunogenicity of planned 17DD-YF primary vaccination. Adults with spondyloarthritis (SpA,n=51) were enrolled along 38 healthy controls (HC), referred for planned vaccination by a rheumatologist. All had low level immunosuppression or had their biological therapy suspended for a period of 5 half-lives before vaccination. The occurrence of AE, neutralizing antibody kinetics, seropositivity rates, 17DD-YF viremia and serum biomarkers levels was evaluated at time points (day 0 (D0), D3, D4, D5, D6, D14, and D28). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score was performed at D0 and D180. Results: Only mild AEs were reported at D28, incidence of local and systemic AEs was similar between SpA and HC groups (4% vs. 8% and 26% vs. 21%; p = 0.65 and 0.8, respectively). The SpA group presented late seroconversion profiles according to the plaque reduction neutralization test (PRNT) related to HC (28% vs. 78% in D14 and 73% vs. 96% at D28, p ≤ 0.001). PRNT titers in the HC group were 440 CI 95% (291-665), higher than in the SpA group, 112 (73-170, p<0.001). The peak of YF viremia was at D5, with a similar number of copies in both groups (8.2 ± 0.7 X 10³ copies / ml in the HC group vs 11.3 x 10³ EAp, p = 0.56). In SpA subgroup (Bio-IT and Non-Bio-IT) analyses, previous biological therapy leads to lower PRNT (Bio-IT 79, 95% CI (39-150) vs. Non-Bio-IT 159, 95% CI (94- 267), p <0.001)). The Non-Bio-IT group achieved a similar response to the HC group (81 vs. 96%, p = 0.112), whereas the Bio-IT group had a lower seroconversion rate (64% vs. 96% HC, p = 0.007). The majority (73%) of SpA patients were in remission or low disease activity, in DO with a mean BASDAI index of 2.7 ± 2.1. In the analysis using the BASDAI score, patients with controlled or active disease (BASDAI<4 or BASDAI≥4) presented similar seroconversion profiles according PRNT at D28 (75% vs. 69%, p=0.6), and low seropositivity rates related to HC (75% vs. 96%, p<0.05) and (69% vs.96%, p<0.05), respectively. PRNT titers in the HC group were 440 95% CI (291-665), higher than in the BASDAI<4 (118, 95% CI (72-193), p<0.01) and BASDAI ≥4 (92, 95% CI(36-239), p<0.01). Higher baseline levels of serum biomarkers were observed in BIO-IT vs Non-Bio-IT as well as in BASDAI≥4 vs BASDAI<4. Increasing levels of several biomarkers were observed in SpA, especially in BIOIT and BASDAI≥4 subgroups, with impaired/disturbed in IFN-g/IL-10 axis around the viremia peak (D5). Conclusion: The 17DD-YF vaccine is safe and effective for SpA patients in the short and long-term. Patients on biological therapy have low baseline levels and lower seroconversion, even after planned suspension. Disease activity by BASDAI score ≥4 did not reduce the immune response. Baseline inflammatory status, previous anti-TNF use, disease activity, and dysfunction of INF-g / IL-10 production at peak viremia may affect the immunogenicity of the 17DD-YF vaccine in patients with spondyloarthritis.