There has been consistent recognition of the need for more objective, precise markers of rheumatoid arthritis (RA) disease progression risk to complement clinical assessments. Recent publications are indicating progress towards development of such tests that will improve monitoring and prediction of disease activity and can better inform treatment selection.
Markers of RA disease susceptibility are also indicative of disease severity and treatment response to tumor necrosis factor (TNF) inhibitor drugs, according to a study published April 28 in the Journal of the American Medical Association (JAMA). The HLA-DRB1 locus, previously tied to disease risk, was found tied to disease outcomes and may be used to better inform RA management, experts say.
The United Kingdom-based researchers utilized data from three large prospective cohorts for discovery as well as validation. Sixteen different HLA-DRB1 haplotypes (amino acids at positions 11, 71, and 74) were evaluated, but the researchers found that the strongest association with radiological damage was seen in RA patients with valine at position 11 of HLA-DRB1. By the five-year follow-up, the percentages of patients with erosions of the hands and feet were: 48 percent of noncarriers of valine at position 11, 61 percent of heterozygote carriers, and 74 percent of homozygote carriers. In patients with inflammatory polyarthritis, valine at position 11 also was associated with significantly higher all-cause mortality and better TNF therapy response (78 percent of noncarriers had moderate or good response versus 81 percent of heterozygote carriers and 86 percent of homozygote carriers).
“These findings may add to the ability to predict outcomes of RA, thus helping to optimize therapeutic strategies for different patients,” writes David Felson, M.D., in an accompanying JAMA editorial. “The way forward in this area will be to use the current genetic findings as one component in the construction of updated prediction algorithms that consider additional genetic differences, environmental and life style factors, biomarkers, and clinical characteristics .”
Economics of Adding Markers of RA Activity into Care
A separate study evaluated the impact a multibiomarker disease activity (MBDA) test has in the management of patients with RA. The authors say that improvements in functional status and lower long-term costs for patients with RA due to treatment alterations based on test results contribute to the test’s cost-effectiveness.
The Vectra DA test (Crescendo Bioscience [CB]; South San Francisco, Calif.) measures serum levels of 12 proteins and uses a validated algorithm to score the level of disease activity in patients with RA. In a study published April 15 in Rheumatology, researchers sought to quantify the downstream effect of using the test on RA-related functional outcomes and costs to private payers and employers. Clinical utility was measured by reported changes to anti-rheumatic drug recommendations following receipt of test results. CB funded the study.
Treatment alterations incorporating Vectra DA test results occurred in 38.0 percent of patient management decisions. Subanalysis indicated that almost 30 percent of these altered decisions increased treatment intensity (drug dosage, formulation, or class), while nine percent of treatment changes resulted in decreased intensity. The researchers found that over 10 years, overall quality-adjusted life years (QALY) increased by 0.08 years and costs decreased by $457. Changes in treatment led to an increase in RA drug costs ($171 per patient in year 1 and $881 over 10 years). However, improvements in patient health status resulted in mean per-patient savings in other direct costs ($150 in year 1 and $661 over the 10 years). This cost savings increased to $6,011 when including both third-party costs and costs related to work productivity. When examining data by disease stage, for patients with early RA the test saved $3,073 and improved QALYs by 0.23 per patient versus adding $275 in costs and a QALY improvement of 0.02 in established RA patients.
“Over a 10-year period, the Vectra DA test costs approximately $22,000 per QALY gained, which is about half of what is considered to be cost-effective medicine,” said Peter Meldrum, CEO of Myriad Genetics, on a May earnings call. (Myriad acquired CB last year.) “This … is further evidence of the value that Vectra DA can bring to the health care system while significantly improving the quality of life for RA patients.”
Takeaway: Emerging markers of RA disease severity and activity are improving clinical management, while possibly saving money in the long-term.