Methotrexate and BAFF interaction prevents immunization against TNF inhibitors

@article{Bitoun2018MethotrexateAB,
  title={Methotrexate and BAFF interaction prevents immunization against TNF inhibitors},
  author={Samuel Bitoun and Ga{\'e}tane Nocturne and Bineta Ly and Roman Krzysiek and Pierre Roques and Alain Pruvost and Audrey Paoletti and Juliette Pascaud and Pierre D{\"o}nnes and Kim Florence and Aude Gleizes and Agn{\`e}s Hincelin-M{\'e}ry and Matthieu Allez and Salima Hacein-Bey-Abina and Fabienne Mackay and Marc Pallardy and Roger Le Grand and Xavier Mariette},
  journal={Annals of the Rheumatic Diseases},
  year={2018},
  volume={77},
  pages={1463 - 1470}
}
Objectives TNF inhibitors (TNFi) can induce anti-drug antibodies (ADA) in patients with autoimmune diseases (AID) leading to clinical resistance. We explored a new way of using methotrexate (MTX) to decrease this risk of immunisation. Methods We treated BAFF transgenic (BAFFtg) mice, a model of AID in which immunisation against biologic drugs is high, with different TNFi. We investigated the effect of a single course of MTX during the first exposure to TNFi. Wild-type (WT) and BAFFtg mice were… Expand
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References

SHOWING 1-10 OF 31 REFERENCES
Antidrug antibodies (ADAb) to tumour necrosis factor (TNF)-specific neutralising agents in chronic inflammatory diseases: a real issue, a clinical perspective
TLDR
A model wherein monitoring of drug levels and ADAb may be a predictive tool leading to a better choice of biologics is proposed, which could improve chronic inflammatory disease management toward a personalized and more cost-effective approach. Expand
Low expression of CD39 on regulatory T cells as a biomarker for resistance to methotrexate therapy in rheumatoid arthritis
TLDR
Methotrexate unresponsiveness in RA is associated with low expression of CD39 on Tregs and the decreased suppressive activity of these cells through reduced ADO production, providing hitherto unrecognized mechanism of immune regulation in RA and on mode of action of MTX. Expand
Anti-adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin-10 gene polymorphisms.
TLDR
The results indicate that IL10 polymorphisms are associated with increased formation of antibodies against adalimumab in RA patients, and these observations are consistent with the reported association of the G8 microsatellite allele with formation of antibody to recombinant FVIII in hemophilia and to nAChR in MG. Expand
Transient Low-Dose Methotrexate Generates B Regulatory Cells That Mediate Antigen-Specific Tolerance to Alglucosidase Alfa
TLDR
It is hypothesized that methotrexate induction treatment concomitant with initial exposure to the biotherapeutic can induce Ag-specific immune tolerance in mice through a mechanism that appears to involve the induction of regulatory B cells. Expand
Concentrations of BAFF correlate with autoantibody levels, clinical disease activity, and response to treatment in early rheumatoid arthritis.
TLDR
Elevated BAFF in a subset of ERA patients is related to autoantibody levels and synovitis, suggesting a rationale to treat ERA patients with BAFF-targeted agents. Expand
Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations
TLDR
Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys. Expand
Methotrexate reduces immunogenicity in adalimumab treated rheumatoid arthritis patients in a dose dependent manner
TLDR
There were remarkable baseline differences: patients developing antiadalimumab antibodies had more long-standing, severe disease and less often used concomitant medication including lower doses of methotrexate (MTX), compared with patients not developing AAA. Expand
Elevated serum BAFF levels are associated with rising anti-double-stranded DNA antibody levels and disease flare following B cell depletion therapy in systemic lupus erythematosus.
OBJECTIVE To determine whether serum BAFF levels correlate with relapse or remission in patients with systemic lupus erythematosus (SLE) following B cell depletion therapy (BCDT) and to assess theExpand
Effect of methotrexate discontinuation on efficacy of seasonal influenza vaccination in patients with rheumatoid arthritis: a randomised clinical trial
TLDR
Temporary MTX discontinuation improves the immunogenicity of seasonal influenza vaccination in patients with RA, and frequency of satisfactory vaccine response 4 weeks postvaccination. Expand
Evaluation of Immunogenicity of Nivolumab Monotherapy and Its Clinical Relevance in Patients With Metastatic Solid Tumors
TLDR
The immunogenicity of nivolumab is not clinically meaningful and the presence of antidrug antibodies was not associated with hypersensitivity, infusion reactions, or loss of efficacy and had minimal impact on nivlumab clearance. Expand
...
1
2
3
4
...