New findings suggest that severity, mortality, and treatment response among persons with rheumatoid arthritis (RA) can be predicted based on genetic haplotype.
The international study was led by Sebastien Viatte, MD, PhD, of the Arthritis Research UK Centre for Genetics and Genomics at the University of Manchester in England. All patients were from the United Kingdom and self-reported themselves as white.
“Advances have been made in identifying genetic susceptibility loci for autoimmune diseases, but evidence is needed regarding their association with prognosis and treatment response,” Viatte and colleagues wrote in their article.1
The study assessed whether specific HLA-DRB1 haplotypes associated with RA susceptibility might also be associated with radiological severity, mortality, and response to tumor necrosis factor (TNF) inhibitors. The Norfolk Arthritis Register (NOAR) of 1691 patients and 2811 radiographs (recruitment took place from 1989-2008, with 2008 as the final follow-up) was used as the discovery cohort, while the Early Rheumatoid Arthritis Study of 421 patients and 3758 radiographs (recruitment from 1986-1999, with 2005 as the final follow-up) served as the independent replication cohort for studies of radiographic outcome.
Evaluation of treatment response came from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort of 1846 patients enrolled at the start of TNF inhibitor therapy (occurrence from 2006-2007, with 2011 as the final follow-up). Mortality was assessed in the NOAR cohort.
Sixteen HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74 were included in the analysis. Radiological outcome used the Larsen score (0 [none] to 200 [severe joint damage]) and erosions of the hands and feet on radiographs. Other outcomes were all-cause mortality and treatment response as measured by change in Disease Activity Score.
The investigators found that among patients with RA, the HLA-DRB1 locus was associated with radiological severity, mortality, and treatment response—this locus is associated with disease susceptibility. Specifically, patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage. The percentages of patients with joint erosions were 48% among noncarriers of valine at position 11, 61% among heterozygote carriers, and 74% among homozygote carriers at year 5.
Valine at position 11 also carried a higher risk of mortality in patients with inflammatory polyarthritis and with better treatment response to TNF inhibitors. A moderate or good response was observed among 81% of heterozygote carriers and 86% of homozygote carriers.
Viatte S, Plant D, Han B, et al. Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response. JAMA. 2015;313(16):1645-1656.