A “Fingerprint” Marker of Fast Progression in RA

Siebuhr, AS, Bay-Jensen AC., Leeming DJ, et al., Serological identification of fast progressors of structural damage with rheumatoid arthritis, Arthritis Research & Therapy (2013) 15:R86 doi:10.1186/ar4266  (Open access)  [epub Aug 14, 2013]

Another biomarker is being proposed to monitor rheumatoid arthritis (RA). A protein “fingerprint” called C1M can not only show disease activity among RA patients, according to studies of patients in a phase III clinical trial, but it can also help monitor drug therapy and detect faster joint damage progression  to identify those in need of more aggressive therapy.
 
The LITHE-biomarker study -- a double-blind, placebo-controlled parallel group study of 585 RA patients (mostly women, mean age 52, RA duration 9 years) – finds that giving tocilizumab (TCZ) plus methotrexate (MTX) reduces baseline levels of  C1M in as little as two weeks.

The biomarker -- a serum protein fingerprint type I collagen degradation mediated by matrix metalloproteinase (MMP)-cleavage (C1M) – was used both as an indicator of treatment efficacy and of structural progression.

Efficacy was measured by improvement in visual analog scale (VAS) pain and disease activity score-28-ESR (DAS28-ESR) at 16, 24 and 56 weeks. Structural progression was defined as radiographic changes in joint space narrowing (JSN) and modified total Sharp score (mTSS).

Changes in JSN and mTSS at 16 weeks (more or less than 35%) were predictive of radiographic damage at 1 year.

Baseline levels of C1M predicted joint damage as well as C-reactive protein (CRP) did.

The LITHE biomarker study was conducted in several stages. Those receiving placebo plus MTX (n=199) experiencing less than 20% improvement in VAS pain, DAS28-ESR, JSN, and mTSS, at week 16 (n=81) were given an “escape” treatment of 4 mg/kg TCZ plus MTX every 4 weeks.

First-step escape patients still not achieving 20% improvement by week 24 were given 8 mg/kg TCZ plus MTX every 4 weeks to 56 weeks.

TCZ responders (>20% improvement) remained on 4 mg/kg TCZ plus MTX for the rest of the study.