Background/Purpose: TNF-Related Apoptosis Inducing Ligand (TRAIL) is a member of the TNF familly. Its soluble receptor Osteoprotegerin (OPG) 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, suggesting that the TRAIL/OPG ratio could be a predictive factor for remission in early arthritis.

Methods: The aim of this study was to confirm these results in the larger French cohort ESPOIR including patients with early arthritis (< 6 months). Patients were assessed for clinical and biological parameters and Sharp’s score at baseline (M0), 12 (M12) and 24 (M24) months. TRAIL and OPG concentrations in serum were measured at M0. We correlated these values with inflammation, 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 those with undifferentiated arthritis (UA). Values of TRAIL and OPG were log transformed to be normalized. Correlations were performed using Pearson tests. For mean comparisons, adjustment with baseline CRP, DAS28, rheumatoid factor, BMI, steroids doses, age and sexe was performed using ANCOVA. Logistic regression was used to determine predictive value for remission (DAS28 ≤2.6) and radiographic progression (DSharp score>0).

Results: TRAIL, OPG and TRAIL/OPG at M0 were not different between patients RA (n = 641) and UA patients (n = 53). Among RA patients, OPG at M0 was significantly correlated with DAS28 (r=0.14; p=0.001), ESR (r=0.14; p=0.001) and CRP (r=0.11; p=0.007). TRAIL/OPG ratio was inversely correlated with DAS28 (r=-0.13; p=0.002), ESR (r=-0.14; p=0.002) and CRP (r=-0.15; p<0.001). TRAIL was only inversely correlated with CRP (r=-0.10; p=0.02). Patients in remission at M12 had a significantly lower concentration of M0 OPG (921±418 (n=204) vs 1014±383 pg/ml (n=342), respectively, p=0.0018). Patients in remission at M12 also tend to have a higher baseline TRAIL/OPG ratio (1.38±1.01 vs 1.17±0.59 pg/ml, p=0.051), but after adjustment, only a low M0 OPG remained significantly associated with remission at M12 (p=0.007). Logistic regression confirmed the predictive value of OPG (OR: 0.21, CI: 0.07-0.067, p=0.008). Patients with progression of Sharp score erosion at M24 have significant higher M0 TRAIL (1128±615, n=334 vs 1010±490 pg/ml, p=0.013). After adjustment, TRAIL is still significantly associated with progression of Sharp score erosion (p=0.003) and logistic regression confirmed that TRAIL is a protective factor for structural damage (OD: 0.22, CI: 0.81-0.609, p=0.003).

Conclusion: Concentrations of TRAIL and OPG could not help in distinguish UA and RA. OPG was correlated with ESR, CRP and DAS28 and TRAIL inversely correlated with CRP. In a larger cohort, this study did not confirm the predictive value of the ratio TRAIL/OPG. However, a low M0 OPG was associated with EULAR remission at M12 and is predictive of remission. A low TRAIL at baseline is associated with Sharp erosion increased at M24 and is also predictive of progression of Sharp’s score erosion.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/osteoprotegerin-and-tnf-related-apoptosis-inducing-ligand-are-respectively-predictive-factors-of-remission-and-erosion-in-early-rheumatoid-arthritis-patients-included-in-the-french-cohort-espoir/