Background/Purpose:
In patients with early RA, autoantibodies, elevated MMP-3, and acute phase
proteins are prognostic biomarkers of joint damage and disease activity.
However, the ability to identify patients most likely to have progressive
disease is limited in those with established RA.

The MOBILITY study (NCT01061736) included MTX
inadequate responder (MTX-IR) RA patients. Two doses of sarilumab (SAR) studied
(200 mg every 2 wks [q2w] and 150 mg q2w) + MTX significantly reduced
radiographic joint damage compared with placebo (Pbo) + MTX, including modified
total Sharp score (mTSS), erosion score (ES), and joint space narrowing (JSN). Mean
change from baseline in mTSS at wk 52 was 0.90 and 0.25 for SAR 150 mg and 200
mg + MTX, respectively, and 2.78 for Pbo + MTX (P<0.0001 vs Pbo). The most common treatment-emergent adverse
events with SAR included infections, neutropenia, injection site reactions, and
increased transaminases. SAR 200 mg + MTX also significantly decreased levels
of bone erosion and joint inflammation markers such as receptor-activated NFκB
ligand (RANKL), MMP-3, and MMP-cleaved fragments of collagen types 1 and 3 (C1M
and C3M) relative to Pbo + MTX.¹ The objective of this study was to
evaluate the prognostic utility of proteins involved in bone resorption and
joint inflammation in patients treated with Pbo + MTX from
the MOBILITY study.

Methods: Serum
markers were measured at baseline and posttreatment in patients receiving Pbo +
MTX (n=128) or subcutaneous SAR 200 mg q2w + MTX (n=131). For baseline analysis,
both treatment groups were included; for posttreatment analysis, only Pbo + MTX
patients were analyzed. Spearman ranked correlations (rho) were calculated
between baseline markers and baseline radiographic scores (x-ray) or DAS28-CRP
for both treatment groups. Correlations between baseline biomarkers and change
from baseline in x-ray scores at wk 52 or DAS28-CRP at wk 24 were calculated
for the Pbo + MTX group. No adjustment for multiplicity was performed.

Results: Correlations
were observed between baseline MMP-3 levels and baseline x-ray scores as well
as wk 52 change from baseline in mTSS and ES (Table). Baseline C1M was associated
with wk 52 JSN progression. Baseline C1M and C3M correlated with baseline DAS28-CRP
(rho = 0.36 and 0.199, respectively; P<0.01).
No significant correlations were identified between baseline levels of RANKL, osteoprotegerin,
OC, or CTX-1 with baseline clinical scores.

Conclusion:
Analysis of markers described in the literature as prognostic of structural
damage and disease activity in MTX-IR patients showed correlation in MOBILITY
patients. These data suggest that multivariate analysis of markers may be
necessary to identify increased risk of joint destruction and elevated disease
activity in patients with established RA.

1. Boyapati et al. Presented
at: ACR; November 14-19, 2014; Boston, MA.