SAT0474 A Proteomic Panel Predicts Drug Response To The Combination of Glucosamine and Chondroitin Sulfate
Authors: V. Kraus, H. Martinez, M. Herrero, J. Verges
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Biomarkers can help identify patients that are more likely to respond favorably to a given therapy (a Predictive or patient stratification biomarker). Biomarkers can also be used to provide objective proof of a biological response to a drug (Efficacy of Intervention biomarker). <h3>Objectives</h3> The overall goal of this project was to identify protein biomarkers that predict likelihood of response to glucosamine hydrochloride and chondroitin sulfate (GH+CS), both predictive and efficacy of intervention biomarkers. We hypothesized that a subset of peptides in a mass spectrometry panel, developed to predict Osteoarthritis (OA) progression, would identify responders to GH+CS, knowing that CS is an NFkB activity and inflammation inhibitor. <h3>Methods</h3> This study analyzed a subset of 80 baseline serum samples from the MOVES (Multicentric Osteoarthritis Intervention Study with SYSADOA) trial<sup>1</sup>. The MOVES trial was an international multicentric, phase IV, double-blind, non-inferiority, randomized trial to compare the efficacy and safety of the combination of glucosamine hydrochloride (GH 1.500mg/day) and chondroitin sulfate (CS 1.200mg/day) known as Droglican® (Bioiberica), versus celecoxib Celebrex (200mg/day) in patients with Kellgren Lawrence grades 2–3 knee OA with severe pain. The sample selected for this study consisted of half drug responders and half non-responders by OARSI-OMERACT criteria. A total of 25 peptides from 23 proteins were analyzed by mass spectrometry. This panel was based on results of discovery proteomic studies in synovial fluid (n=23), urine (n=45) and serum (n=40) from knee OA subjects to identify biomarkers indicative of an OA diagnosis and OA progression. Quantitative LC/MRM was performed on a 1 μg of protein digest spiked with 10 fmol of 25 stable isotope labeled peptides using a nanoAcquity UPLC system (Waters Corp) coupled to a Waters Xevo TQ-S triple quadrupole mass spectrometer via a nanoelectrospray ionization source. Technical variability (based on spiked in yeast alcohol dehydrogenase was 10.4%). Logistic regression was used to evaluate the association of demographics (age, gender and BMI) and the biomarkers with drug response (yes/no) after 180 days of treatment. P values &lt;0.05 were considered significant. <h3>Results</h3> The sample was 90% female, mean age 64 (SD 7) years, 55% with BMI &gt;30 kg/m<sup>2</sup>. Higher age (p=0.004) but neither gender, nor KL grade were associated with likelihood of drug response. Age plus the marker panel significantly predicted drug response (overall model p=0.0007). In the multivariable logistic regression, adjusted for age, a total of 12 peptides, corresponding to 11 proteins, were significantly independently associated with drug response (p&lt;0.0001 by Effect likelihood Ratio tests). <h3>Conclusions</h3> These biomarkers in theory could be used to stratify different patient groups in terms of likelihood of clinical response to GH+CS in efforts to develop personalized treatment algorithms for OA patients. <h3>References</h3> Hochberg et al. ARD 2015. <h3>Disclosure of Interest</h3> None declared