Serological identification of fast progressors of structural damage with rheumatoid arthritis.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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


BACKGROUND
ClinicalTrials.gov: NCT00106535.
Anne Sofie
AS
Siebuhr
Anne C
AC
Bay-Jensen
Diana J
DJ
Leeming
Adam
A
Plat
Inger
I
Byrjalsen
Claus
C
Christiansen
Désirée
D
van de Heijde
Morten A
MA
Karsdal
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy; D015415:Biomarkers / Q000097:blood*; D024042:Collagen Type I / Q000097:blood*; D018450:Disease Progression; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood*; D011859:Radiography
D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; C502936:tocilizumab