Outcomes of COVID-19 in patients with rheumatoid arthritis: A multicenter research network study in the United States

Raiker, Rahul; DeYoung, Charles; Pakhchanian, Haig; Ahmed, Sakir; Kavadichanda, Chengappa; Gupta, Latika; Kardeş, Sinan

doi:10.1016/j.semarthrit.2021.08.010

Cited by 66 publications

(70 citation statements)

References 32 publications

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“…These genes (such as SERPINE1 and IL-1β) are also implicated in the pathogenesis of thrombosis in COVID-19 [ 19 ]. Similar findings of increase VTE risk during COVID-19 has also been reported for rheumatoid arthritis [ 23 ]. It can also be due to hyper viscosity, endothelial dysfunction, down-regulation of protein C, and inhibition of fibrinolysis caused by inflammatory cytokines like TNF alpha and IL-1 [ 24 , 25 ].…”

Section: Discussionsupporting

confidence: 86%

Axial spondyloarthritis may protect against poor outcomes in COVID-19: propensity score matched analysis of 9766 patients from a nationwide multi-centric research network

et al. 2021

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Section: Discussionsupporting

confidence: 86%

Axial spondyloarthritis may protect against poor outcomes in COVID-19: propensity score matched analysis of 9766 patients from a nationwide multi-centric research network

et al. 2021

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“…Patients with rheumatoid arthritis (RA) are at higher risk of hospitalisation and death by COVID-19 due to comorbidities6–8 or immunosuppressive treatments 6–9. Moreover, patients with RA have reduced immunogenicity to COVID-19 vaccines10–21 when using rituximab,11–17 abatacept,11 12 17 methotrexate (MTX)11–13 18–21 and glucocorticoids 10–12 18…”

Section: Introductionmentioning

confidence: 99%

Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial

et al. 2022

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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.

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“…The COVID-19 has proven to be a major threat to individuals worldwide 1. Patients with rheumatoid arthritis (RA), one of the most common autoimmune rheumatic diseases (ARD),2 are at a high risk of severe COVID-19 outcomes,3–5 especially those with active disease, under immunosuppressive therapies, or with comorbidities 5 6. In this context, mass vaccination is the main measure to control the pandemic.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Outcomes of COVID-19 in patients with rheumatoid arthritis: A multicenter research network study in the United States

Cited by 66 publications

References 32 publications

Axial spondyloarthritis may protect against poor outcomes in COVID-19: propensity score matched analysis of 9766 patients from a nationwide multi-centric research network

Axial spondyloarthritis may protect against poor outcomes in COVID-19: propensity score matched analysis of 9766 patients from a nationwide multi-centric research network

Two-week methotrexate discontinuation in patients with rheumatoid arthritis vaccinated with inactivated SARS-CoV-2 vaccine: a randomised clinical trial

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

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