Background TNF-Related Apoptosis Inducing Ligand (TRAIL) is a member of the TNF familly. Osteoprotegerin (OPG) is a soluble receptor of TRAIL that also inhibits Receptor activator of nuclear factor kappa-B ligand (RANKL). We previously reported that, in a cohort of early arthritis(< 2 years), a high TRAIL/OPG ratio at baseline was associated with remission (DAS28<2.6) at 6 months. This result suggested that the TRAIL/OPG ratio could be used as a predictive factor for remission in early arthritis.
Objectives The aim of this study was to confirm these results in a larger cohort. We measure TRAIL and OPG in sera from patients included in the French cohort ESPOIR. We correlated these values with disease activity and radiographic progression. We also aimed to compare TRAIL and OPG between patients with arthritis responding to ACR/EULAR 2010 criteria (RA) and the undifferentiated arthritis (UA).
Methods To be included in the French cohort ESPOIR, patients should have an early arthritis (< 6 months). Patients were assessed for clinical and biological parameters at baseline, 6, 12, and 24 months and for radiographic progression at baseline, 12 and 24 months (Sharp’s score). TRAIL and OPG in serum were measured at inclusion (M0) and at 12 month follow-up. Values were normalized using logOPG and logTRAIL. Cytokine levels between groups were compared using the unpaired t-test with significance set to p <0.05. Correlations were performed using Pearson tests. Changes between baseline and 12 months were assessed using paired t-test. Adjustment was performed using ANCOVA on normalized values.
Results TRAIL, OPG and TRAIL/OPG at baseline were not different between RA patients (n = 641) and UA patients (n = 53). Among RA patients, OPG was significantly correlated at baseline with DAS28(r=0.14; p<0.001), ESR (r=0.17; p<0.001) and CRP (r=0.13; p<0.001). At inclusion, TRAIL/OPG ratio was inversely correlated with DAS28(r=-0.11; p=0.006), ESR (r=-0.15; p<0.001) and CRP (r=-0.16; p<0.001). TRAIL was only inversely correlated with CRP (r=-0.10; p=0.02). For RA patients followed at 12 months (n = 571), we oberved a significant decrease of DAS28 (mean±SD from 5.3 [4.6-6.2] to 3.1 [2.2-4.1]; p<0.001) and in TRAIL (-249±596 pg/ml; p<0.001) and OPG concentrations (-128±403 pg/ml; p<0.001). TRAIL/OPG ratio remained stable. Patients in EULAR remission at 12 months (n = 206) had a significantly lower baseline concentration of OPG than patients who were not in remission (n = 349) (921±418 vs 1014±383 pg/ml, respectively, p=0.001). Patients in remission at 12 months (n = 206) also had a significantly higher baseline TRAIL/OPG ratio (1.40±1.02 vs 1.18±0.60 pg/ml, p=0.04). After adjustment for DAS28, CRP and age at inclusion, OPG at baseline remained significantly lower in patients in remission at 12 months (p=0.007) whereas it was no significant anymore for the ratio TRAIL/OPG (p=0.13).
Conclusions Concentrations of TRAIL and OPG could not help in distinguish undifferentiated arthritis and RA. OPG was correlated with ESR, CRP and DAS28 and TRAIL inversely correlated with CRO. OPG and TRAIL significantly decreased between M0 and M12. This study does not confirm the predictive value of the ratio TRAIL/OPG. However, a low OPG value at baseline was associated with EULAR remission at 12 months.
Acknowledgements We also wish to thank The French Society of Rheumatology which supported ESPOIR cohort study and our work. We also wish to thank N. Rincheval who did expert monitoring and data management, V. Dechauvelle and C. Lukas for expert x-ray reading and all the investigators who recruited and followed the patients
Disclosure of Interest None Declared