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

Abstract

ObjectivesTo 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).MethodsThis 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.ResultsPatients 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.ConclusionsPatients 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 detailsNCT04754698.

Strong response after fourth dose of mRNA COVID-19 vaccine in autoimmune rheumatic diseases patients with poor response to inactivated vaccine

“…We identified that prednisone in doses ≥7.5 mg/day and rituximab have a negative impact on immune response after the fourth dose in poor/non-responder patients, as also reported by our group after prime vaccination [ 7 , 10 , 17 ]. With regard to LEF, its negative effect on immunogenicity observed in the present study is probably related to the fact that all patients used this drug in association with other DMARDs, as observed in an RA population immunized with Sinovac-CoronaVac vaccine [ 7 ]. In contrast to SSc and RA, SLE patients tended to have higher rates of positive antibody responses.…”

“…The detrimental effect of immunosuppressive therapy on antibody production has been previously demonstrated in ARD patients [ 1 , 7 , 8 , 17 ]. We identified that prednisone in doses ≥7.5 mg/day and rituximab have a negative impact on immune response after the fourth dose in poor/non-responder patients, as also reported by our group after prime vaccination [ 7 , 10 , 17 ].…”

“…The detrimental effect of immunosuppressive therapy on antibody production has been previously demonstrated in ARD patients [ 1 , 7 , 8 , 17 ]. We identified that prednisone in doses ≥7.5 mg/day and rituximab have a negative impact on immune response after the fourth dose in poor/non-responder patients, as also reported by our group after prime vaccination [ 7 , 10 , 17 ]. With regard to LEF, its negative effect on immunogenicity observed in the present study is probably related to the fact that all patients used this drug in association with other DMARDs, as observed in an RA population immunized with Sinovac-CoronaVac vaccine [ 7 ].…”

“…Similarly, for hepatitis B virus vaccine, booster doses were required for achievement of adequate responses in ARD patients on biological therapy, particularly rituximab [ 6 ]. With regard to anti-SARS-CoV-2 vaccination, prime immunization may be especially impaired by age ≥60 years, prednisone, and some specific immunosuppressive and biological drugs [ 1 , 7 , 8 ], reinforcing the need for additional doses. Both homologous and heterologous third dose of anti-SARS-CoV-2 vaccination have been associated with robust humoral response in this population [ 9 , 10 ].…”

Serological Response to BNT162b2 Anti-SARS-CoV-2 Vaccination in Patients with Inflammatory Rheumatic Diseases: Results From the RHEUVAX Cohort

“…Data on methotrexate, JAKi, and abatacept were judged not yet consistent/robust (9). Meanwhile, more data for ABA and JAKi are coming to light from studies with sample sizes ranging to 11 to 54 patients demonstrating reduction in antibody titers (10)(11)(12)(13).…”