Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers

Abstract

Background/PurposeTo evaluate biomarkers as predictors of impending erosion progression.MethodsVariables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations.ResultsOut of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP).ConclusionsAdding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.

Osteoclast microRNA Profiling in Rheumatoid Arthritis to Capture the Erosive Factor

“…(4) No existing set of biomarkers in patients with early arthritis adequately identifies the potential to develop erosions, the elusive "erosive factor." Adding a high serum level of 14-3-3η to antibodies (rheumatoid factor [RF] and anti-citrullinated protein antibodies [ACPA]) and C-reactive protein (CRP) somewhat improved the prediction of impending rapid erosive progression, (5) but models still lack high predictive value that would be clinically actionable. (6) As a multifactorial and polygenic disorder, RA involves both genetics and environment in its pathogenesis.…”

“…In a current Canadian multicenter study of early RA, bone erosions were already present at presentation in 25% to 30% and new erosive disease developed over the next year in 10% to 25% more. ( 4 ) No existing set of biomarkers in patients with early arthritis adequately identifies the potential to develop erosions, the elusive “erosive factor.” Adding a high serum level of 14‐3‐3η to antibodies (rheumatoid factor [RF] and anti‐citrullinated protein antibodies [ACPA]) and C‐reactive protein (CRP) somewhat improved the prediction of impending rapid erosive progression, ( 5 ) but models still lack high predictive value that would be clinically actionable. ( 6 )…”

Biomarkers for the diagnosis and treatment of rheumatoid arthritis-a systematic review

“…16 Also, impending Rapid Erosive Progression (REP) prediction improved by adding high 14-3-3η to RF and CRP in a cohort of 749 RA patients as prospectively investigated by Carrier N, et al, which may help to adapt treatment strategies in at-risk individuals, even those with signs of erosion. 17 Similarly, Ziegelasch M, et al, demonstrated that anti-CCP prospectively predicted radiographic damage of early RA patients, but was not associated with disease activity and recommended that close radiographic monitoring is warranted in anti-CCP positive patients with early RA, regardless of disease activity. 18 In addition to this, RA-related ultrasound changes were tested in correlation to anti-CCP levels by Tan YK et al, and found significant correlation (r=0.46, P=0.048) and predictive ability (P=0.048).…”

“…42 Adding 14-3-3η to positive RF and high CRP improved prediction of radiographic erosion progression (REP). 17 The strength of this study is the large sample size of real-world patients (749) with a prospective design reflecting day to day clinical practice. However, the observational design could have limited exploring whether intensive therapy in high-risk patients would prevent or delay REP. Anti-CCP has also been identified as a marker of radiographic damage, but not disease activity, being in line with a previous study.…”

New laboratory biomarkers of rheumatoid arthritis

“…Учитывая роль 14-3-3η в индукции синтеза ММП, представляют интерес его исследования в качестве биомаркера костного метаболизма при РА. Повышение концентрации 14-3-3η (в сочетании с СРБ) у пациентов на ранних стадиях РА ассоциируется с высоким риском развития эрозий [62,64]. При этом снижение концентрации 14-3-3η на фоне терапии коррелирует с уменьшением риска развития эрозий и клинической активности заболевания [65,66].…”