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Abstract
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.
Trial registration details NCT04754698.
- Arthritis
- Rheumatoid
- Covid-19
- vaccination
- biological therapy
- therapeutics
Data availability statement
All data relevant to the study are included in the article. Not applicable.
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Data availability statement
All data relevant to the study are included in the article. Not applicable.
Footnotes
Handling editor Josef S Smolen
Contributors ACM-R, CGSS, EFNY, SGP, EGK, NEA and EB conceived and designed the study. EB is responsible for the overall content as the guarantor. ACM-R, CGSS, EFNY, SGP, CAS, TP, LdVKK, NEA and EB participated in data collection and analysis and supervised clinical data management, writing of the manuscript and revision of the manuscript. LdVKK, TP and EB organised and supervised blood collection and vaccination protocol. Pasoto supervised serum processing, SARS-CoV-2-specific antibody ELISA/neutralisation assays and SARS-CoV-2 RT-PCR. ACM-R, KRB, DSD, AYS, HCdS, CGSS, EFNY, SGP, CAS, TP, LdVKK, CSRA, MSRS, TLN, GGMB, EGK, NEA and EB collected epidemiological and clinical data and assisted with the identification of SARS-CoV-2 infection and follow-up of patients. All authors helped to edit the manuscript.
Funding This study was sponsored by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (number: 2015/03756–4 to NEA, SGP, CAS and EB; number: 2017/14352–7 to TP; number: 2019/17272–0 to LdVKK; and number: 2021/06613–0 to TLN); Conselho Nacional de Desenvolvimento Científico e Tecnológico (number: 305242/2019–9 to EB and number: 304984/2020–5 to CAS) and B3, Bolsa de Valores do Brasil. Instituto Butantan supplied the study product and had no other role in the trial.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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