HLA-DRB1 Alleles Augment RA Severity and TNF Inhibitor Responses Save

The HLA-DRB1 haplotype is a known risk factor for RA. Viatta and researchers from the UK Norfolk Arthritis Register (NOAR) analyzed their cohorts and found that among those with the HLA-DRB1 genotypes, the presence of valine at position 11 not only increased risk but also compouned disease severity with more early erosions, higher all-cause mortality rates and, conversely, better EULAR responses to TNF inhibitor therapy.

In an accompanying JAMA editorial, Felson and Klareskog note that modern advances have resulted in less disease severity in the last view decades, however a 20% poor response rate, higher cardiovascular mortalities are still observed. Integration of these genotypically influential findings into a better understanding of the pathogenesis of RA seems likely. Moreover, genotyping becomes one of several integral factors (environmental, stochastic, biomarkers, epigenetics) that can guide a more intelligent algorithmic approach to RA therapy.