Rheumatoid Arthritis

Providing critical insights across the continuum of patient care for diagnosis, prognosis, and disease activity monitoring of rheumatoid arthritis.

What is Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a chronic, progressive and often debilitating inflammatory disease that causes pain, stiffness, swelling and loss of function in the joints.¹

WHO reports that 18 million people worldwide are living with RA. Approximately 1.5 million Americans and 250,000 Canadians live with RA.^2,3

Clinical gaps in RA and the Patient Impact

Early RA Diagnosis

Standard tests like RF and anti-CCP only detect 50% of early RA cases, leaving many patients without timely intervention.⁴

If treatment doesn’t begin within two years of symptom onset, remission rates plummet to just 10-33%.⁵

Prognosis

Standard of care tests have limited ability to stratify and triage patients into risk categories, which is crucial for identifying the right treatment strategies.⁶

Treatment Monitoring

Identifying an effective therapy is time consuming. It can take up to six months to determine if a treatment is effective.⁷ Biologic switching is common: 30-40% of patients do not respond to anti-TNFs, 23% need to try two biologics, and 17% require 3 or more.⁸

Flares and Risk of Damage

Flares are common and difficult to predict, increasing the likelihood of ongoing joint damage.

26% to 39% of individuals with RA experience flares within one to two years of remission, with frequent flares increasing the risk of radiographic progression.^9,10

Supporting the Continuum of Care and Patient Journey

14-3-3eta is a mechanistic and modifiable biomarker, providing clinical utility from early diagnosis to remission

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14-3-3eta complements RF and anti-CCP to enable earlier, more accurate diagnosis of RA

High Sensitivity & Specificity

14-3-3eta is highly sensitive and specific for diagnosing early and established RA.^11,12

Seronegative RA

14-3-3eta is valuable in detecting RA in RF/anti-CCP seronegative patients.¹³

Complements Existing Markers

When combined with RF and anti-CCP, 14-3-3eta improves diagnostic accuracy.¹¹

Predictive Value

Elevated 14-3-3eta levels are associated with higher disease activity and flare risk.^14,15

14-3-3eta-identifies-patients-that-are-RF-and-anti-CCP-seronegative---2

14-3-3eta is modifiable and its levels inform disease severity and therapy response

Serial decreases of 14-3-3eta levels in response to therapy are associated with better clinical outcomes.^16,17,18

Levels of 14-3-3eta ≥0.5 ng/mL indicates a higher risk of radiographic progression and flare, even in patients who are in SDAI remission.^16-18

Serial increases or sustained 14-3-3eta levels are associated with worse outcomes, and indicates treatment options should be reassessed.^17,19

14-3-3eta complements CRP testing, providing better joint damage prediction than either marker alone, and supports tight-control treatment strategies.^15,19,20

Example of serial testing of 14-3-3eta every 3 months

14-3-3eta is a modifiable biomarker and an independent predictor of radiographic progression and disease activity in rheumatoid arthritis. 14-3-3eta levels indicate joint damage risk, and serial testing helps closely monitor patient response to therapy. Combining 14-3-3eta with CRP improves joint damage prediction and supports tight-control treatment strategies:

Decreases in 14-3-3eta levels in response to therapy are associated with better clinical outcomes.^16-18
Increases or sustained 14-3-3eta levels, particularly ≥ 0.50 ng/mL, indicates significant joint damage risk and are associated with a worse prognosis.^19,20
High CRP (>8.0 mg/L) combined with elevated 14-3-3eta (≥0.50 ng/mL) represents an adverse prognostic signature, and together, these markers provide better prediction of joint damage than either marker alone.^19,20

Strategies for effective remission maintenance and flare risk prediction

Guidance for Remission Maintenance

Monitoring 14-3-3eta and CRP can help identify patients at higher risk of radiographic progression, aiding in more informed decisions on dose tapering and remission maintenance.^19,20

Predictive Value for Flare Risk

Higher 14-3-3eta levels at baseline, especially when combined with low CRP, are strong predictors of flare risk in patients discontinuing biologic therapy.¹⁵

The 14-3-3eta protein is a joint-derived, proinflammatory mediator that is implicated in the joint erosion process and pathogenesis of rheumatoid arthritis.¹⁴

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References

References:

World Health Organization. Rheumatoid arthritis. 2023, June 28. https://www.who.int/news-room/fact-sheets/detail/rheumatoid-arthritis
Arthritis Foundation. Rheumatoid Arthritis: Causes, Symptoms, Treatments and More. 2021, Oct 15. https://www.arthritis.org/diseases/rheumatoid-arthritis
Arthritis Society Canada. Rheumatoid Arthritis Symptoms and Diagnosis. 2023, Sep. https://arthritis.ca/about-arthritis/arthritis-types-(a-z)/types/rheumatoid-arthritis/rheumatoid-arthritis-symptoms-and-diagnosis
UpToDate. Diagnosis and differential diagnosis of rheumatoid arthritis. 2024, Mar 21. https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-rheumatoid-arthritis
Arthritis Foundation. Your RA is in Remission! Now What? https://www.arthritis.org/health-wellness/treatment/treatment-plan/disease-management/your-ra-is-in-remission!-now-what
Ursum J, Bos WH, van Dillen N, Dijkmans BA, van Schaardenburg D. Levels of anti-citrullinated protein antibodies and IgM rheumatoid factor are not associated with outcome in early arthritis patients: a cohort study. Arthritis Res Ther. 2010;12(1):R8.
Smolen JS, Landewé R, Bijlsma J, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis. 2017;76(6):960-977.
Mease PJ, Stryker S, Liu M, et al. Treatment patterns in rheumatoid arthritis patients newly initiated on biologic and conventional synthetic disease-modifying antirheumatic drug therapy and enrolled in a North American clinical registry. Arthritis Res Ther. 2021;23(1):236.
Chaiamnuay S, Jiemjit S, Songdechaphipat W, Narongroeknawin P, Pakchotanon R, Asavatanabodee P. Predictors of flare in rheumatoid arthritis patients with persistent clinical remission/low disease activity: Data from the TARAC cohort. Medicine (Baltimore). 2022;101(32):e29974.
Smolen JS, Pedersen R, Jones H, Mahgoub E, Marshall L. Impact of flare on radiographic progression after etanercept continuation, tapering or withdrawal in patients with rheumatoid arthritis. Rheumatology (Oxford). 2020;59(1):153-164.
Maksymowych WP, van der Heijde D, Allaart CF, et al. 14-3-3η is a novel mediator associated with the pathogenesis of rheumatoid arthritisand joint damage. Arthritis Res Ther. 2014;16(2).
Maksymowych WP, Naides SJ, Bykerk V, et al. Serum 14-3-3η is a novel marker that complements current serological measurements to enhance detection of patients with rheumatoid arthritis. J Rheumatol. 2014;41(11):2104-2113.
Abdelhafiz D, Kilborn S, Bukhari M. The Role of 14-3-3 η as a Biomarker in Rheumatoid Arthritis. Rheumatol Immunol Res. 2021;2(2):87-90.
Naides SJ, Marotta A. 14-3-3η in “Seronegative” Rheumatoid Arthritis. J Rheumatol. 2015;42(10):1995.
Hirata S, Marotta A, Hanami K, et al. SAT0062: 14-3-3ETA predicts joint damage progression and flaring after adalimumab discontinuation. Annals of the Rheumatic Diseases. 2017;76:791.
Sornasse T, Chahal S, Gui Y, et al. AB0104: 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. Annals of the Rheumatic Diseases. 2020;79:1351.
Hirata S, Marotta A, Gui Y, Hanami K, Tanaka Y. Serum 14-3-3η level is associated with severity and clinical outcomes of rheumatoid arthritis, and its pretreatment level is predictive of DAS28 remission with tocilizumab. Arthritis Res Ther. 2015;17:280.
Shovman O, Gilburd B, Watad A, et al. 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.
Carrier N, Marotta A, de Brum-Fernandes AJ, et al. Serum levels of 14-3-3η protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis. Arthritis Res Ther. 2016;18:3.
Carrier N, de Brum-Fernandes AJ, Liang P, et al. Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers. RMD Open. 2020;6(1):e001191.