Rheumatoid arthritis

RA gene linked with disease severity, treatment response

Wednesday, 29 Apr 2015

Genetic variations associated with the risk of rheumatoid arthritis have been linked to treatment response, the risk of death, and severity of disease in a study published in JAMA.

The HLA-DRBl locus was associated with radiological severity of RA, risk of death, and response to treatment with TNF inhibitor therapy in the study of over 6,000 RA patients from two study cohorts and a registry.

Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (OR, 1.75 [95% CI, 1.51-2.05], P = 4.6) as measured by Larsen score, reported the researchers led by Anne Barton from the University of Manchester in England.

“Valine at this position represents what we believe is the strongest single genetic association with radiographic damage identified to date,” they wrote.

Valine at position 11 also was associated with higher all-cause mortality in patients with inflammatory polyarthritis (hazard ratio, 1.16 [95% CI, 1.03-1.31], P = .01) and with better EULAR response to TNF inhibitor therapy (OR, 1.14 [95% CI, 1.01-1.30], P = .04)

“Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRBl haplotype analysis for management of RA,” the authors concluded.

Commenting on the findings David T. Felson from the Boston University School of Medicine, and Lars Klareskog of the Karolinska Institute in Stockholm said while they did not have immediate clinical implications the identification of the precise HLA variants that influence disease course was of “great interest”.

“[the findings] also help to inform understanding of disease pathogenesis by strongly implicating HLA-dependent immune events not only for the onset of RA, but also for disease course and mortality,” they wrote in an accompanying editorial.

“These observations open the door to further research, including replication for this haplotype and discovery related to its combination with other determinants of disease development and progression,” they wrote.

“Such discoveries will prove helpful both to understand and predict the variable disease course and response to therapy that occurs in patients with rheumatoid arthritis.”

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