Early changes in serum type ii collagen biomarkers predict radiographic progression at one year in inflammatory arthritis patients after biologic therapy

Abstract

Objective. To investigate whether short-term changes in serum biomarkers of type II collagen degradation (C2C) and types I and II collagen degradation (C1,2C), as well as the biomarker for the synthesis of type II procollagen (CPII) can predict radiographic progression at 1 year following initiation of biologic therapy in patients with inflammatory arthritis.Methods. Serum levels of biomarkers were measured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflecting changes from baseline in all 3 biomarkers (⌬COL) was calculated. Associations with clinical responses according to the 28-joint count Disease Activity Score and with radiographic progression according to the modified Sharp/van der Heijde score (SHS) were assessed.Results. The 1-year increase in the SHS correlated with the 1-month change in C2C results (r ‫؍‬ 0.311, P ‫؍‬ 0.028) and the ⌬COL score (r ‫؍‬ 0.342, P ‫؍‬ 0.015). Radiographic progression was predicted by increases in serum C2C at 1 month (P ‫؍‬ 0.031). The ⌬COL score was significantly associated with 1-year radiographic progression after 1 (P ‫؍‬ 0.022), 3 (P ‫؍‬ 0.015), 6 (P ‫؍‬ 0.048), and 9 (P ‫؍‬ 0.019) months of therapy. Clinical remission was predicted by 1-month decreases in serum levels of C2C (P ‫؍‬ 0.008) and C1,2C (P ‫؍‬ 0.036). By regression analysis, 1-month changes in C2C, C1,2C, and CPII levels were independently associated with, and correctly predicted radiographic outcome in, 88% of the patients.Conclusion. Short-term changes in serum levels of collagen biomarkers following initiation of biologic therapy may better predict long-term clinical and radiographic outcomes. These collagen biomarkers may therefore be valuable new early indicators of short-term biologic treatment efficacy in clinical trials and in individual patients with inflammatory erosive arthritis.Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are forms of progressive inflammatory arthritis characterized by pain and progressive destruction of the joints. Joint destruction occurs when inflamed synovial tissue erodes and degrades adjacent cartilage and bone through the action of locally produced cytokines and metalloproteinases (1). This process can be measured by quantifying the changes in joint space narrowing and erosions that are visible on serial plain radiographs (2). Radiographic joint damage is associated with long-term functional disability (3) and is the accepted assessment tool for monitoring clinical progression and long-term response to therapy (4). Radiographic progression develops over many months and years, however, and is not suitable for assessment of treatment efficacy over short periods.

Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis

“…Further, we showed that a direct longitudinal relationship exists between clinically perceptible signs of arthritis and degradation of CTX-I and especially CTX-II 14. These and other studies15–17 suggest that in RA urinary excretion of CTX-II and other cartilage degradation markers most likely represents joint cartilage, whereas excretion of CTX-I, less prominently associated with clinical signs of arthritis, most likely represents both generalised and localised bone loss 18 19…”

Synovial tissue research: a state-of-the-art review

“…It is known that collagen biomarker and MMP levels predict radiographic progression of RA, and therefore may act as a prognostic biomarker. 135,136 A study with the primary objective of attempting to understand more about the mechanism of action of methotrexate (19 subjects) and leflunomide (16 subjects) demonstrated that MMP-1 was significantly reduced by both. The level of TIMP-1 was significantly reduced in the leflunomide-treated patients, but not the methotrexate-treated patients.…”

The role of biomarkers in the management of patients with rheumatoid arthritis

“…Mullan et al [43] showed that short-term change in serum biomarkers of type 2 collagen degradation (C2C), types 1 and 2 collagen degradation (C1,2C), and the biomarker for type 2 procollagen synthesis (CPII) correlated with radiographic progression following initiation of biologic therapy in patients with RA and psoriatic arthritis. Oneyear radiographic progression was predicted by increases in serum C2C at 1 month (P = 0.031) and clinical remission by reduction in serum levels of C2C (P = 0.008) and C1,2C (P = 0.036) at 1 month.…”