“Is my treatment working?” “I’m not doing well, but my labs are always fine.” “My doctor says I’m in remission, but I don’t agree.” — a few of the worries that people with rheumatoid disease (PRD) often share.
For years RPF has helped people with worries like these to be informed about research, options, and strategies to manage the disease. Recently on the blog, we discussed the protein called 14-3-3η first recognized about 14 years ago. Research has shown it has a key role in the processes of joint damage and progression of rheumatoid disease. Let’s look at how it can specifically help people who are using various disease treatments.
A study found 57% of patients were positive for 14-3-3η before treatment started, and only 37% were still positive after five months of treatment. And those who still were positive had significantly lower levels following treatment. Importantly, the 14-3-3η levels correlated strongly with disease activity improvement measures. Patients who are negative and symptoms have improved do better and the result informs whether their treatment is working. That is why it is critical to measure 14-3-3η levels every 3 months. The study concluded that for many patients treated with tofacitinib, the 14-3-3η test can serve as an objective biomarker for monitoring therapy response.
A study of people treated with tocilizumab for one year showed that patients whose levels of 14-3-3η reverted to negative had a better clinical response than patients who remained positive. Pretreatment test levels were also predictive of remission at one year. The study found the levels linked to treatment outcomes: “Serial decreases in 14-3-3η levels in response to therapy are associated with better clinical outcomes, whereas increases or sustained levels of the marker are associated with a worse prognosis.”
Another study showed that levels of 14-3-3η correlated with clinical measures of disease activity when people are treated with upadacitinib also. After 24 weeks, upadacitinib reduced levels of 14-3-3η and this correlated with the clinical measures.
The challenge of testing in rheumatoid disease
In a disease that reflects the uniqueness of each person’s immune system, finding objective measures of disease activity or treatment response has been challenging. One key to good treatment is the use of a combination of measures including both patient centered outcome measures and lab tests (biomarkers) that correlate well with a patient’s disease activity. The 14-3-3η test is valuable in people treated with these medications (IL-6 inhibitors and JAK inhibitors) and possibly with others also.
The future of RA treatment
For almost 10 years, RPF has advocated for expansion of tools for measuring disease activity and improved understanding of the disease to make possible the optimal use of existing treatments. The 14-3-3η test is a great example—it can sometimes detect disease activity when other disease measures do not because it measures a protein that other tests don’t. In the future, rheumatoid disease therapy will be better targeted to specific patient’s unique needs. Better measuring tools are a key step in that process.
Where to get a 14-3-3η test for yourself or a family member:
Hirata S, Marotta A, Hanami K, Tanaka Y. 14-3-3eta Predicts Joint Damage Progression and Flaring after Adalimumab Discontinuation. Ann Rheum Dis 2017;76:791 (abstract SAT0061). Available from: https://ard.bmj.com/content/annrheumdis/76/Suppl_2/791.3.full.pdf
Sornasse T, Chahal S, Gui Y, Nagarajan N, Friedman A, Biln N. Correlation of Plasma 14-3-3η Levels with Disease Activity Measures in Methotrexate Naïve RA Patients Treated With Upadacitinib Monotherapy in the Select-Early Phase 3 Study. Ann Rheum Dis 2020;79:1351. Available from: https://ard.bmj.com/content/79/Suppl_1/1351.2
Shovman O , Gilburd B , Watad A , Amital H, Langevitz P, Bragazzi NL , Adawi M, Perez D , Lidar M, Katz I , Blank M , Biln NK , Marotta A, Shoenfeld Y. Decrease in 14-3-3η protein levels is correlated with improvement in disease activity in patients with rheumatoid arthritis treated with Tofacitinib. Pharmacol Res 2019;141:623-626. Available from: https://doi.org/10.1016/j.phrs.2018.11.009