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

Abstract

Background/purpose: To evaluate biomarkers as predictors of impending erosion progression.

Methods: Variables 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.

Results: Out 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).

Conclusions: Adding 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.

Keywords: 14-3-3η; Anti-CCP2 antibodies; CRP; Radiographic progression; Recent-onset inflammatory arthritis; Rheumatoid factor.

Figure 1

Flowchart of patient enrollment process. Patients were excluded when alternative diagnoses such as microcrystalline arthritis or a defined connective tissue disease became apparent over follow-up. Patients were removed by the team during follow-up, when repeatedly not compliant or too sick (usually from associated comorbidities) to come to their follow-up appointments. A few patients were also removed by the treating rheumatologist when their disease was no longer active and follow-up was not felt to be clinically justified. ‘Visits not done’ refer to missed visits at that specific evaluation, while ‘planned visits’ refer to visits to be done after the report date.