1389: The New Serum Synovial Biochemical Marker HELIX-III Predicts Radiological Progression in Early Arthritis Independently of Usual Risk Factors

Patrick Garnero¹, Evelyne Gineyts¹, Jean-Charles Rousseau¹, Pascal Richette², Jérémie SELLAM³ and Roland Chapurlat¹, ¹INSERM 1033, Lyon, France, ²Department of Rheumatology, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France, ³Sorbonne Universite, AP-HP, Saint-Antoine hospital, Paris, France

Background/Purpose: The prognosis of rheumatoid arthritis (RA) is highly variable across patients (P.) and difficult to predict. Usual risk factors, e.g., radiological joint damage, increased CRP and ACPA positivity lack sensitivity. Biochemical markers of cartilage degradation may improve prediction, but sensitive biological indicators of synovial metabolism are lacking, although synovial inflammation is a major driver of disease progression. The aim of this study was to investigate the value of serum HELIX-III, a new ELISA-based biochemical marker of synovial collagen degradation, to predict progression of joint damage in a prospective longitudinal cohort of P. with early arthritis.

Methods: Patients from the prospective ESPOIR French cohort included 788 P. with definitive or probable clinical diagnosis of RA or a diagnosis of undifferentiated arthritis with potential for progression to RA. All P. presented with swelling of two or more joints, 6 weeks to 6 months symptom duration and no previous treatment with DMARD or glucocorticoids. Hand and feet radiographs were obtained at baseline and after 1- and 5-year follow-up and scored centrally for bone erosion, joint space narrowing (JSN) and total damage by the modified van der Heijde Sharp scoring method. Progression was defined as an increase of 1 or 5 unit(s) between baseline and 1 or 5 years, respectively. The association between baseline serum HELIX-III levels (SD standardized continuous values or in quintiles) and progression was assessed by logistic regression.

Results: At baseline, serum Helix-III levels were higher in ACPA positive P. and those with RA (p=0.0001). They were positively correlated with DAS28-VS (p< 0.0001), CRP (p< 0.0001) and erosion score (p=0.017). The table shows the 5-year relative risk (RR) and 95 % CI of progression for each SD increase of baseline Helix-III levels.

5-year progression in	RR (95% CI) of progression for each SD increase of baseline HELIX-III
	Adj. for gender, BMI, RA diagnosis	Additionally adj. for ACPA, DAS28, CRP
Erosion	1.55 (1.12-2.14)	1.51(1.00- 2.30)
JSN	1.54(1.14-1.74)	1.27 (0.97-1.65)
Total damage	1.51(1.21-1.87)	1.34 (1.01-1.76)

When P. were categorized in quintiles (Q) of Helix-III levels, P. in the highest Q had a 5-year fully adjusted RR (95% CI) of total damage progression of 2.45 (1.36-2.44) compared to P. in the four other Q. Patients with erosion at baseline had a corresponding RR of progression of 2.09 (1.24-3.33) vs P. with no erosion. Subjects with both high Helix-III and erosion had a RR of 4.75 (1.47-15.3) indicating an additive effect of the two predictors. When analyses were restricted to P. with RA, the 5-yr fully adjusted RR (95%CI) of total damage progression was 1.49 (1.13-1.97) for each SD increase in Helix-III. At 1 year, HELIX-III was also associated with the risk of erosion progression [RR (95% CI) per SD increase: 1.60 (1.16-2.20) after full adjustment].

Conclusion: Increased serum Helix-III is consistently associated with a higher short and long-term risk of progression, independently of major risk factors, in P. with early arthritis. Serum Helix-III may be useful- in association with other risk factors such as erosion- to identify P. with early arthritis at higher risk.

Disclosures: P. Garnero, None; E. Gineyts, None; J. Rousseau, None; P. Richette, AbbVie, Amgen, Biogen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB; J. SELLAM, None; R. Chapurlat, Novartis, Pfizer.