Distinct impact of DMARD combination and monotherapy in immunogenicity of an inactivated SARS-CoV-2 vaccine in rheumatoid arthritis

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Medeiros-Ribeiro, Ana Cristina ; Bonfiglioli, Karina Rossi ; Domiciano, Diogo Souza ; Shimabuco, Andrea Yukie ; da Silva, Henrique Carrico ; Saad, Carla G. S. ; Yuki, Emily Figueiredo Neves ; Pasoto, Sandra Gofinet ; Renner Araujo, Carlo Scognamiglio ; Nakai, Tatiane Lie ; Silva, Clovis Artur ; Pedrosa, Tatiana ; Kanda Kupa, Leonard de Vinci ; Rodrigues Silva, Matheus Santos ; Moreira Balbi, Guilherme Guimaraes ; Kallas, Esper Georges ; Aikawa, Nadia Emi ; Bonfa, Eloisa

• Tipo de documento: Artigo Científico
• Fonte: ANNALS OF THE RHEUMATIC DISEASES; v. 81, n. 5, p. 10-pg., 2022-02-07.

Resumo

Objectives To evaluate the distinct impact of disease modifying antirheumatic drugs (DMARD) combination and monotherapy in immune response to an inactivated SARS-CoV-2 vaccine in patients with rheumatoid arthritis (RA). Methods This phase 4 prospective study analysed seroconversion (SC) of anti-SARS-CoV-2 immunoglobulin G (IgG) and neutralising antibodies (NAb) induced by the inactivated vaccine (CoronaVac) in patients with RA in comparison to controls (CG). Disease activity and treatment were also assessed. Only participants with baseline negative IgG/NAb were included. Results Patients with RA (N=260) and CG (N=104) had comparable median ages (59 years (50-65 years) vs 58 years (49.8-64 years), p=0.483). Patients with RA had moderate but lower SC (61.8% vs 94.2%, p<0.001) and NAb positivity (45% vs 78.6%, p<0.001) in comparison to CG after full vaccination. Baseline disease activity did not influence immunogenicity (p>0.05). After multivariate analyses, factors independently related to reduced SC were: older age (OR=0.79 (0.70-0.89) for each 5-year interval, p<0.001), methotrexate (OR=0.54 (0.29-0.98), p=0.044), abatacept (OR=0.37 (0.19-0.73), p=0.004) and number of DMARD (OR=0.55 (0.33-0.90), p=0.018). Regarding NAb, age (OR=0.87 (0.78-0.96) for each 5-year interval, p=0.007) and prednisone >7.5 mg/day (OR=0.38 (0.19-0.74), p=0.004) were negatively related to the presence of NAb. Further comparison of SC/NAb positivity among RA treatment subgroups and CG revealed that methotrexate/tofacitinib/abatacept/tocilizumab use, in monotherapy or in combination, resulted in lower responses (p<0.05), while tumour necrosis factor inhibitor and other conventional synthetic DMARD interfered solely when combined with other therapies. Conclusions Patients with RA under DMARD have a moderate immunogenicity to CoronaVac. We identified that nearly all DMARD combinations have a deleterious effect in immunogenicity, whereas a more restricted number of drugs (methotrexate/tofacitinib/abatacept/tocilizumab) also hampered this response as monotherapy. These findings reinforce the need of a broader approach, not limited to specific drugs, to improve vaccine response for this population. (AU)

• Processo FAPESP: 21/06613-0 - Imunogenicidade e segurança da vacina CoronaVac em pacientes com doenças reumatológicas autoimunes doença: artrite reumatoide
• Beneficiário: Tatiane Lie Nakai
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 17/14352-7 - Avaliação da relevância dos níveis sanguíneos de drogas utilizadas em doenças autoimunes reumatológicas no acompanhamento da segurança, eficácia e aderência à terapêutica
• Beneficiário: Tatiana Do Nascimento Pedrosa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/17272-0 - Avaliação da relevância dos níveis sanguíneos de drogas utilizadas em doenças autoimunes reumatológicas no acompanhamento da segurança, eficácia e aderência à terapêutica
• Beneficiário: Leonard de Vinci Kanda Kupa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/03756-4 - Avaliação da relevância dos níveis sanguíneos de drogas utilizadas em doenças autoimunes reumatológicas no acompanhamento da segurança, eficácia e aderência à terapêutica
• Beneficiário: Eloisa Silva Dutra de Oliveira Bonfá
• Modalidade de apoio: Auxílio à Pesquisa - Temático