Biomarker 14-3-3eta Reflects RA Disease Activity, Treatment Response

Researchers have now publicly reported data to support use of the marker 14-3-3eta as a supplemental test in assessment of rheumatoid arthritis (RA). Seropositivity for 14-3-3eta indicates more severe disease activity, while low titers of the biomarker may indicate a good response to anti-tumor necrosis-alpha (TNFα) therapy, according to a report at the EULAR conference in Madrid by Walter Maksymowych MD, a professor of rheumatology at the University of Alberta, and others.

An analysis of serum 14-3-3eta in banked blood samples from 112 patients with established and early RA from three study cohorts, these results held even in those patients with low C-reactive protein (CRP) levels.

The soluble marker 14-3-3eta is a regulatory intracellular protein that activates pro-inflammatory cytokines that drive joint damage. An assay for 14-3-3eta is being marketed in the US as a laboratory-developed test.

Levels of 14-3-3eta were measured at baseline in patients with established RA from the RAPPORT cohort (n=75) and the early RA TEACH and COBRA cohorts (n=37). The majority were women with a median age of 57 and were biologic-nave. Among the total group, 92 (82%) were 14-3-3 eta positive and 20 (18%) tested negative.

The 75 patients with established RA in the RAPPORT trial were given anti-TNFα therapy, and 14-3-3eta serum was measured at around 15 weeks post-treatment. Among these patients, the 20% who achieved a Good EULAR response had significantly lower median 14-3-3eta at baseline (0.72 ng/ml) compared to those who did not respond as well (2.52 ng/ml).
 
Low CRP did not correspond with treatment response. Among the 36% (n=27) of the 75 RAPPORT patients who had a baseline CRP ≤ 10mg/L, the seven (26%) who achieved a Good EULAR response had a nearly undetectable median 14-3-3 eta, while the 20 patients who did not respond had median levels of 3.5ng/ml at baseline.

Although the EULAR abstracts are no longer available online, an image of the poster, reproduced on a patient-authored blog has been publicized on social media. It has generated robust response from patients with RA curious about whether and how to obtain the test.