Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarticular joint inflammation resulting in massive tissue turnover. The turnover is partly mediated by an up-regulation of proteolytic enzymes, such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMPs responsible for the degradation of the extracellular matrix (ECM).2 The MMP-mediated degradation of the main joint ECM proteins (eg, types I and III collagen)3 results in the release of specific biomarkers such as the connective tissue biomarkers C1M and C3M,4,5 known as protein fingerprints. These biomarkers are direct measures of changes to the tissue affected by the disease, in contrast to measurement of acute reactants such as C-reactive protein (CRP) or interleukin 6 (IL-6), which are upstream of tissue changes.6 Thus, protein fingerprint biomarkers may be more sensitive tools for measuring disease changes or changes caused by intervention. Protein fingerprint biomarkers have been associated with disease progression and response to therapy.7,8 CRPM is a protein fingerprint formed through degradation of CRP. In response to IL-6, CRP is secreted by the liver as an acute phase reactant.9 C-reactive proteinaccumulates in inflamed tissue, where it is degraded by MMPs, resulting in the release of CRPM.10 The ratio of C3M to CRPM may depict MMP3 is 1 of the MMPs responsible for the degradation of the ECM; its expression is highly elevated in the affected joint and may therefore be a relevant marker of proteolytic activity.2
Tocilizumab (TCZ) is approved in 2 doses for intravenous infusion:4 and 8 mg/kg. Although both doses provide structural progression and symptomatic relief, 8 mg/kg generally affords a higher level of response.11 Composite quantifiable measures depending on CRP were more reduced in 8 mg/kg compared with 4 mg/kg.12,13 As there are more adverse events in the higher dose,14 identification of those patients who respond most optimally to 4 mg/kg would significantly improve the benefit-to-risk assessment. The aim of present study was to identify responders to 4 mg/kg TCZ by measuring protein fingerprints at baseline.