ObjectiveTo evaluate the effect on immunogenicity and safety of 2-week methotrexate (MTX) discontinuation after each dose of the Sinovac-CoronaVac vaccine versus MTX maintenance in patients with rheumatoid arthritis (RA).MethodsThis was a single-centre, prospective, randomised, investigator-blinded, intervention study (NCT04754698, CoronavRheum) including adult patients with RA (stable Clinical Disease Activity Index (CDAI) ≤10, prednisone ≤7.5 mg/day) randomised (1:1) to withdraw MTX (MTX-hold) for 2 weeks after each vaccine dose or maintain MTX (MTX-maintain), evaluated at day 0 (D0), D28 and D69. Coprimary outcomes were anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC) and neutralising antibody (NAb) positivity at D69. Secondary outcomes were geometric mean titres (GMT) and flare rates. For immunogenicity analyses, we excluded patients with baseline positive IgG/NAb, and for safety reasons those who flared at D28 (CDAI >10) and did not withdraw MTX twice.ResultsRandomisation included 138 patients with 9 exclusions (5 COVID-19, 4 protocol violations). Safety evaluation included 60 patients in the MTX-hold and 69 patients in the MTX-maintain group. Further exclusions included 27 patients (13 (21.7%) vs 14 (20.3%), p=0.848) with positive baseline IgG/NAb and 10 patients (21.3%) in MTX-hold with CDAI >10 at D28. At D69, the MTX-hold group (n=37) had a higher rate of SC than the MTX-maintain group (n=55) (29 (78.4%) vs 30 (54.5%), p=0.019), with parallel augmentation in GMT (34.2 (25.2–46.4) vs 16.8 (11.9–23.6), p=0.006). No differences were observed for NAb positivity (23 (62.2%) vs 27 (49.1%), p=0.217). At D28 flare, the rates were comparable in both groups (CDAI, p=0.122; Disease Activity Score in 28 joints with C reactive protein, p=0.576), whereas CDAI >10 was more frequent in MTX-hold at D69 (p=0.024).ConclusionWe provided novel data that 2-week MTX withdrawal after each dose of the Sinovac-CoronaVac vaccine improves anti-SARS-CoV-2 IgG response. The increased flare rates after the second MTX withdrawal may be attributed to the short-term interval between vaccine doses. This strategy requires close surveillance and shared decision making due to the possibility of flares.

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.

No abstract

BACKGROUNDWe recently reported an attenuate immunogenicity in patients with autoimmune rheumatic diseases. However, the effect of spondyloarthritis (SpA) and its treatment on COVID-19 vaccine immunogenicity remains to be determined for this group of patients. We therefore aimed to evaluate humoral immune responses to inactivated SARS-CoV-2 vaccine (CoronaVac) in patients with SpA (axial spondyloarthritis and psoriatic arthritis) taking DMARDs and commonly used targeted biological therapies, compared with a control group (CG). METHODSProspective observational cohort patients diagnosed with 194 SpA and 183 CG were vaccinated with CoronaVac in two doses with a 28-days interval. One hundred ninety-four patients completed the study and could be paired with CG for immunogenicity analysis. Blood samples were collected in the days 0, 28 and 69 (D69) to evaluate anti-SARS-CoV-2 IgG seroconversion (SC) and presence of neutralizing antibodies (NAb) in participants with negative IgG and NAb at baseline. RESULTSPatients and GC were comparable regarding age (p = 0.93) and sex (p = 1.00). Immunogenicity at D69 showed a moderate/high SC (80.2% vs. 95.7%, p < 0.0001) and NAb positivity (61.6% vs. 82.7%, p < 0.0001) in SpA but lower than CG. Factors associated with lower immunogenicity were older age (56.8 vs. 51.4; p = 0.03318) and higher frequencies of prednisone (25.7% vs. 4.2%; p = 0.0004), methotrexate (51.4% vs. 40.1%, p = 0.0016) and TNF inhibitor (TNFi) (62.9% vs. 34.5%, p = 0.0035). Likewise, prednisone (17.6% vs. 2.8%, p = 0.0013) and TNFi (50% vs. 33.9%; p = 0.0408) were associated with diminished NAb positivity. Sulfasalazine was associated with higher SC rates (8.6% vs. 26.8%, p = 0.0246) and NAb positivity (13.2% vs. 29.4%, p = 0.0168). The multivariate analysis revealed that older age (p = 0.037), prednisone (p = 0.001), TNFi (p = 0.016), and methotrexate (p = 0.017) were independently associated with lower SC while prednisone (p = 0.006) and TNFi (p = 0.027) were also associated with reduced NAb response. CONCLUSIONOur finding of an excellent safety and moderate/high SC rate in SpA supports the recommendation of CoronaVac vaccination. The impaired immune response in the minority of patients under immunosuppressive and biological therapy requires novel strategies to enhance antibody response in this subgroup of patients.

No abstract