Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients

  title={Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients},
  author={Lydia R. Coulthard and John C. Taylor and Stephen Eyre and James I. Robinson and Anthony G. Wilson and John Dudley Isaacs and Kimme L. Hyrich and Paul Emery and Anne Barton and Jennifer H. Barrett and Ann W. Morgan and Michael F. McDermott},
  journal={Annals of the Rheumatic Diseases},
  pages={103 - 98}
Background Rheumatoid arthritis (RA) does not always respond to available treatments, including tumour necrosis factor (TNF) antagonists. A study was undertaken to investigate whether genetic variation within genes, encoding proteins in the p38 signalling network, contributes to the variable response to TNF antagonists. Methods 1102 UK Caucasian patients with RA receiving anti-TNF therapy (infliximab, adalimumab and etanercept) were genotyped for 38 pairwise-tagging single nucleotide… 

Replication of Association of the PTPRC Gene With Response to Anti–Tumor Necrosis Factor Therapy in a Large UK Cohort

Test of established RA susceptibility variants, including PTPRC, in the prediction of response to TNF blockade in a large cohort of patients from the UK found presence of the rs10919563 RA susceptibility variant at thePTPRC gene locus predicts improved response to anti-TNF biologic therapy.

Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNF&agr; inhibitors in patients with rheumatoid arthritis

No SNPs associated with treatment response to TNF&agr; inhibitors are found in a genome-wide association study of 196 genetically homogenous Danish patients with RA and in a meta-analysis of available studies.

Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rheumatoid arthritis

Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available and single nucleotide polymorphisms associated with anti-TNF treatment response in RA map to genes involved in T cell function, NFκB and TNF signalling pathways.

CD6 and Syntaxin Binding Protein 6 Variants and Response to Tumor Necrosis Factor Alpha Inhibitors in Danish Patients with Rheumatoid Arthritis

Background TNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis

PTPRC has become the most replicated genetic biomarker of response to TNFi, and the positive but weaker replication of IL10 and CHUK should stimulate further validation studies.

A longitudinal genome-wide association study of anti-tumor necrosis factor response among Japanese patients with rheumatoid arthritis

This is the first genome-wide association study (GWAS) to identify genetic biomarkers of anti-TNF response among Japanese RA patients, using response at 2 time-points for a more reliable clinical phenotype over time.

Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response

Of the various protein biomarkers studied, rheumatoid factor and/or anticitrullinated protein autoantibodies may have a future role in predicting response or guiding the order in which to use biological agents.

Genetic and genomic predictors of anti-TNF response.

Emerging genome-wide association studies suggest that there may be a number of genes with modest effects on treatment response rather than a few genes of large effect, which may identify those most likely to respond to anti-TNF therapy.

Evidence of NLRP3-inflammasome activation in rheumatoid arthritis (RA); genetic variants within the NLRP3-inflammasome complex in relation to susceptibility to RA and response to anti-TNF treatment

Evidence of modulation of theNLRP3-inflammasome in patients with RA prior to receiving infliximab is found and some evidence of association for SNPs at NLRP3 and CARD8 loci with RA susceptibility and response to anti-TNF is found.

Pharmacogenetics: Reality or Dream in Predicting the Response to TNF-α Inhibitor Treatment?

  • Biology, Medicine
  • 2013
Background: The ongoing progresses in the knowledge of the pathogenic mechanisms of various immunemediated or inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, Crohn’s



Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis.

The findings suggest the potential for genotype at these markers to aid selection of anti-TNF agent in patients with RA is suggested, although preliminary data must be regarded as preliminary and will require replication in further large cohorts of pro-tumour necrosis factor-treated patients.

A single tumour necrosis factor haplotype influences the response to adalimumab in rheumatoid arthritis

Preliminary data indicating that a single TNF locus haplotype, present on both chromosomes is associated with a lower response to ADA, mainly in patients treated with ADA and MTX is provided.

Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis

The presence of RF or anti-CCP antibodies was associated with a reduced response to anti-TNF drugs and it is likely that genetic factors will contribute to treatment response, but these do not include the well established RA susceptibility loci, SE and PTPN22.

Predictors of response to anti-TNF-alpha therapy among patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register.

Data support an improved outcome among patients receiving MTX in combination with anti-TNF-alpha therapies, and the most disabled patients were less likely to respond, despite concurrent MTX, as well as the association of smoking and poor outcome with INF.

TNF-α −308 G/A polymorphism and responsiveness to TNF-α blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis

The clinical utility of prospectively genotyping for this variant when initiating anti-TNF-α therapy for RA should now be formally assessed, indicating that the −308(A) variant predicts poor response to TNF- α inhibitors.

Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register.

In this observational study of patients with established RA, gender did not predict response to anti-TNF therapy, whereas treatment with concomitant DMARDs, especially MTX and low disability were associated with good response.

Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha.

Preliminary results support the hypothesis that TNF alpha is an important regulator in RA, and suggest that it may be a useful new therapeutic target in this disease.

C-reactive protein as a predictor of infliximab treatment outcome in patients with rheumatoid arthritis: defining subtypes of nonresponse and subsequent response to etanercept.

CRP suppression at week 12 in the NRs was associated with a late clinical improvement with infliximab treatment (24 weeks), whereas failure to suppress the CRP atweek 12 was associatedWith a good response on switching to etanercept.

Efficacy and safety of the anti-TNF biologic agents

  • A. Weaver
  • Biology, Medicine
    Modern rheumatology
  • 2004
The role of TNF in inflammation and RA is explained, the mechanisms of action, efficacy, and safety profiles of the various FDA-approved TNF inhibitors are compared and contrast, and potential explanations for the clinical differences observed between these agents are offered.