ARTHRITIS & RHEUMATISM Vol. 56, No. 9, September 2007, pp 2919–2928 DOI 10.1002/art.22843 © 2007, American College of Rheumatology Early Changes in Serum Type II Collagen Biomarkers Predict Radiographic Progression at One Year in Inflammatory Arthritis Patients After Biologic Therapy Ronan H. Mullan, 1 Clare Matthews, 1 Barry Bresnihan, 1 Oliver FitzGerald, 1 Lindsay King, 2 A. Robin Poole, 3 Ursula Fearon, 1 and Douglas J. Veale 1 Objective. To investigate whether short-term changes in serum biomarkers of type II collagen degra- dation (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 mea- sured at baseline and at 1, 3, 6, 9, and 12 months after initiation of biologic therapy. A composite score reflect- ing 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 as- sessed. Results. The 1-year increase in the SHS corre- lated 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 in- creases 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 asso- ciated with, and correctly predicted radiographic out- come 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 radio- graphic 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 de- velops over many months and years, however, and is not suitable for assessment of treatment efficacy over short periods. Dr. Mullan’s work was supported by a grant from the Health Research Board of Ireland. Collagen biomarker assay work was supported by Shriners Hospitals for Children, Montreal, Quebec, Canada. 1 Ronan H. Mullan, MRCP, Clare Matthews, MD, Barry Bresnihan, MD, FRCP, Oliver FitzGerald, MD, FRCP, FRCPI, Ursula Fearon, PhD, Douglas J. Veale, MD, FRCPI: St. Vincent’s University Hospital, and the Conway Institute of Molecular Medicine, Dublin, Ireland; 2 Lindsay King, PhD: Ibex Pharmaceuticals, Montreal, Quebec, Canada; 3 A. Robin Poole, PhD, DSc: Shriners Hospitals for Children, and McGill University, Montreal, Quebec, Canada. Dr. Bresnihan has received an honorarium (less than $1,000) from Wyeth for advisory board participation. Drs. King and Poole own stock or stock options in Ibex Pharmaceuticals. Dr. Poole has received consulting fees (more than $10,000) from Ibex Pharmaceuticals and is an inventor with Shriners Hospitals for Children on patents for C1,2C, C2C, CPII, and CS-846 assays, for which he receives royalties. Address correspondence and reprint requests to Douglas J. Veale, MD, FRCPI, Department of Rheumatology, St. Anthony’s Clinic, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. E-mail: douglas.veale@ucd.ie. Submitted for publication June 9, 2006; accepted in revised form May 18, 2007. 2919