Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control

Dinis, Valquíria Garcia; Viana, Vilma T; Leon, Elaine Pires; Silva, Clóvis A.; Saad, Carla G. S.; Moraes, José Reinaldo da Silva Cabral de; Bonfá, Eloísa; Medeiros-Ribeiro, Ana Cristina

doi:10.1007/s10067-020-04932-9

Cited by 3 publications

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References 29 publications

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“…Specifically, the exclusive evaluation of patients without combination therapy highlighted abatacept as related to vaccine non-response, even in monotherapy, in comparison to other DMARD. The impact of abatacept on vaccination confirms previous evidence from influenza A/H1N1,36–38 and pneumococcal conjugate vaccines,39 probably due to the attenuation of co-stimulating signal of naïve T cells, inhibition of T cell proliferation, and inadequate stimulation of B cells 40 41…”

Section: Discussionsupporting

confidence: 83%

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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Section: Discussionsupporting

confidence: 83%

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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“…For example, denatured g-globulins acquire antigenicity by exposing new antigenic determinants, thereby inducing autoantibodies (rheumatoid factors). 29 Besides, the body's regulation of autoreactive B cells is also very important. It is known that in mice, their T S cells are significantly reduced with an increase in their age.…”

Section: Autoimmune Inflammatory Diseasesmentioning

confidence: 99%

Recent advances on drug delivery nanoplatforms for the treatment of autoimmune inflammatory diseases

et al. 2022

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“…Exceptions to this are Abatacept, a Cytotoxic T Lymphocyte Antigen-4-immunoglobulin (CTLA-4-Ig) fusion protein, and the checkpoint inhibitors anti-CTLA-4 and anti-Programmed Cell Death Protein 1 (PD1). Abatacept prevents engagement of the costimulatory molecule CD28 on the T cell surface with its activating ligands expressed by DC there by inhibiting T cell activation (14) and is used clinically to treat Rheumatoid arthritis (RA) patients (15)(16)(17). Checkpoint inhibitors conversely prevent the inhibition of T cell and other immune cell activation by cancer cells and have been approved for the use in a number of otherwise difficult to treat malignant diseases (18).…”

Section: Introductionmentioning

confidence: 99%

A discovery pipeline for identification and in vivo validation of drugs that alter T cell/ dendritic cell interaction

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et al. 2022

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The interaction between T cells and dendritic cells (DC) is central to determining whether or not an adaptive immune response develops. Autoimmune diseases like rheumatoid arthritis result from inappropriate activation of self-antigen specific T cells, therefore targeting the interaction between T cells and DCs is of considerable therapeutic interest. Here, we describe the development and validation of a drug development platform that includes a high-throughput image-based screening assay and a complementary in vivo model. The in vitro assay directly measures the ability of compounds to influence the interaction of T cells with DC, both negatively and positively. While the in vivo model allows the validation of hit molecules directly in the lymph nodes of intact animals. Using this pipeline, we identify a new function for the protein kinase inhibitor AS703569 by inhibiting T cell/ DC interactions in vitro and in vivo.

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Abatacept induced long-term non-progressive reduction in gamma-globulins and autoantibodies: dissociation from disease activity control

Cited by 3 publications

References 29 publications

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

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

Recent advances on drug delivery nanoplatforms for the treatment of autoimmune inflammatory diseases

A discovery pipeline for identification and in vivo validation of drugs that alter T cell/ dendritic cell interaction

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