Open Access Open Badges Research article

Serological identification of fast progressors of structural damage with rheumatoid arthritis

Anne Sofie Siebuhr1*, Anne C Bay-Jensen1, Diana J Leeming1, Adam Plat2, Inger Byrjalsen1, Claus Christiansen3, Désirée van de Heijde4 and Morten A Karsdal1

Author Affiliations

1 Nordic Bioscience, Herlev Hovedgade, DK-2730 Herlev, Denmark

2 Roche Pharmaceuticals, Shire Park, 1 Falcon Way, Welwyn Garden City, Hertfordshire AL7 1TW, UK

3 Centre of Clinical and Basic Research, Telegrafvej 4, DK-2750 Ballerup, Denmark

4 Department of Rheumatology, Leiden University, Albinusdreef 2, NL-2333 Leiden, The Netherlands

For all author emails, please log on.

Arthritis Research & Therapy 2013, 15:R86  doi:10.1186/ar4266

Published: 14 August 2013



Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruction. We investigated whether baseline serum C1M levels could identify structural progressors and if the biomarker levels changed during anti-inflammatory treatment with tocilizumab (TCZ).


The LITHE-biomarker study (NCT00106535, n = 585) was a one-year phase III, double-blind, placebo (PBO)-controlled, parallel group study of TCZ 4 or 8 mg/kg every four weeks, in RA patients on stable doses of methotrexate (MTX). Spearman's ranked correlation was used to assess the correlation between baseline C1M levels and structural progression at baseline and at weeks 24 and 52. Multivariate regression was performed for delta structural progression. Change in C1M levels were studied as a function of time and treatment.


At baseline, C1M was significantly correlated to C-reactive protein (P <0.0001), visual analog scale pain (P <0.0001), disease activity score28-erythrocyte sedimentation rate (DAS28-ESR) (P <0.0001), joint space narrowing (JSN) (P = 0.0056) and modified total Sharp score (mTSS) (P = 0.0006). Baseline C1M was significantly correlated with delta-JSN at Week 24 (R2 = 0.09, P = 0.0001) and at Week 52 (R2 = 0.27, P <0.0001), and with delta-mTSS at 24 weeks (R2 = 0.006, P = 0.0015) and strongly at 52 weeks (R2 = 0.013, P <0.0001) in the PBO group. C1M levels were dose-dependently reduced in the TCZ + MTX group.


Baseline C1M levels correlated with worsening joint structure over one year. Serum C1M levels may enable identification of those RA patients that are in most need of aggressive treatment

Trial registration NCT00106535

Structural progression; Connective tissue degradation; Biochemical marke; Identification of patients