Crescendo Bioscience, Inc. presents 8 posters and 2 oral presentations on the development of molecular diagnostic tests for rheumatoid arthritis at the European League Against Rheumatism (EULAR) 2010 Congress, June 16-19, 2010, in Rome, Italy

Crescendo Bioscience presented new data on the development of a test to quantify disease activity in rheumatoid arthritis – Vectra™ DA – at EULAR 2010. In an oral presentation¹, Guy Cavet, Senior Director of Informatics, discussed how biomarkers to be included in the test were selected and prioritized on the basis of early discovery² and algorithm development studies in over 1100 patient samples from 3 study groups (InFoRM, BRASS, and OMRF), which included patients with a wide spectrum of disease activity. Additional data presented discussed the independent validation of the pre-specified 12-biomarker test in 230 independent patients with a range of disease activity scores.

Data on the performance of Vectra DA in an independent patient population (the CAMERA study group) were also presented³. The CAMERA study had previously shown that intensive treatment with methotrexate, driven by regular clinical assessment of disease activity aiming at remission, could improve patient outcomes in early rheumatoid arthritis (RA). Measures of disease activity using Vectra DA in 120 patient samples were highly correlated with clinical measures of disease activity (DAS-28) and were found to decrease in response to treatment. These presentations were accompanied by posters providing further information on the biomarkers⁴ and development process⁵ and describing the high precision and reproducibility⁶ of Vectra DA under multiple laboratory conditions.

Crescendo scientists and their colleagues also presented early data from the development of a test to measure structural damage in rheumatoid arthritis. In one study, biomarkers from blood and urine were studied in relationship to joint damage as evaluated by radiographic imaging in 24 patients followed for 2 years⁷. For the wide range of biomarkers examined, serum proteins were found to have the strongest correlations to predicting joint damage progression. Blood biomarkers were further examined in patients from the BeST trial, a 5-year blinded study comparing treatments for aggressive early rheumatoid arthritis⁸. 90 individual biomarkers were measured in longitudinal serum samples from these patients. Blood-based biomarkers measuring the current rate of joint destructive damage could identify patients at risk for accelerated bone and cartilage damage.

Finally, in a second oral presentation, Michael Centola, Crescendo Bioscience Founder and Scientific Advisor, discussed biomarkers of coronary atherosclerosis in patients with rheumatoid arthritis⁹. In data from 196 rheumatoid arthritis patients participating in the ESCAPE RA study, elevations in apolipoprotein complexes containing ApoC-III particles were strongly predictive of progression of coronary atherosclerosis in RA, suggesting that defects in apolipoprotein complex metabolism and triglyceride transport may contribute to accelerated atherosclerosis in RA, and could form the basis of a standardized assay to identify patients at high risk for coronary vascular disease.

BeST = Clinical and Radiographic Outcomes of Four Different Treatment Strategies in Patients With Early Rheumatoid Arthritis (the BeSt Study): A Randomized, Controlled Trial

BRASS = Brigham and Women’s Rheumatoid Arthritis Sequential Study

CAMERA = Computer Assisted Management in Early Rheumatoid Arthritis

ESCAPE RA = Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis

InFoRM = Index for Rheumatoid Arthritis Measurement

OMRF = Oklahoma Medical Research Foundation

_______________________________________________

¹DEVELOPMENT OF A MULTI-BIOMARKER TEST FOR RHEUMATOID ARTHRITIS (RA) DISEASE ACTIVITY G. Cavet¹, M. Centola², Y. Shen¹, D. Haney¹, D. Smith¹, L. Hesterberg¹, D. Chernoff¹, J. Carulli³, N. A. Shadick⁴, M. E. Weinblatt⁴, M. Hamburger⁵, R. Fleischmann⁶, E. C. Keystone⁷, J. R. Curtis⁸ and The InFoRM and BRASS Study Groups ¹Crescendo Bioscience, Inc., S San Francisco, CA, ²OMRF, Oklahoma City, OK, ³Biogen Idec, Cambridge, MA, ⁴Brigham & Women's Hosp, Boston, MA, ⁵Rheumatology Associates of Long Island, Melville, NY, ⁶Metroplex Clinical Research Center, Dallas, TX, ⁸University of Alabama at Birmingham, Birmingham, AL, United States, ⁷Mt. Sinai Hospital, Toronto, Canada

² SAT0518

³ FRI0106

⁴ FRI0034

⁵ THU0066

⁶ THU0065

⁷ THU0485

⁸ SAT0049

⁹ELEVATIONS IN APOC-III CONTAINING APOLIPOPROTEIN COMPLEXES PREDICT PROGRESSION OF CORONARY ATHEROSCLEROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS N. Knowlton¹, J. T. Giles², J. Wages¹, A. Payne¹, G. Cavet³, M. Centola¹, P. Alaupovic¹, J. M. Bathon², ¹OMRF, Oklahoma City, OK, ²Johns Hopkins University School of Medicine, Baltimore, MD, ³Crescendo Bioscience, Inc., S. San Francisco, United States

Crescendo Bioscience™ Presentations from the 73rd Annual Meeting of the American College of Rheumatology

Crescendo Bioscience presented three studies on the development of biomarker-based assays to monitor rheumatoid arthritis (RA) at the 73rd Annual Meeting of the American College of Rheumatology in Philadelphia on October 16-21, 2009. Each of these studies represented the analysis of multiple quantitatively assessed serum biomarkers for association with specific facets of RA disease, with the overall goal of enhancing current measures to provide improved patient care.

In a poster presentation entitled "Stepwise Development of a Multi-Protein Biomarker Index of RA Disease Activity," Crescendo researchers and collaborators from the BRASS registry reported on the successive refinement of statistical models to associate candidate serum protein biomarkers with the severity of RA disease activity, as measured by DAS28 scores. The analysis was based on robust quantitative assays for an initial set of 121 proteins — representing a diverse set of biological pathways — from RA patient serum, and demonstrated the superior predictive value of a multi-protein biomarker index as compared to any single measure. This work forms the basis for development of a commercial assay.

In a poster presentation entitled "Predicting Radiographic Progression in Rheumatoid Arthritis with Ultrasound and Biomarkers," Crescendo researchers and collaborators reported on a study to associate blood-based biomarkers with joint destruction in RA, as measured by radiographic assays. A statistical model based on multiple biomarkers from patients followed in a 2-year blinded study of early aggressive RA produced results that strongly correlated with rates of radiographic progression and joint damage.

In an oral presentation entitled "The Apolipoprotein Complex LpAII:B:C:D:E Is Increased in Rheumatoid Arthritis and Is Associated with Carotid Atherosclerosis," Crescendo researchers and collaborators addressed the increased risk of cardiovascular disease in RA patients, which is not accounted for by conventional measures of lipid markers alone. They found a novel association of increased levels of the triglyceride carrier apolipoprotein complex LpAII:B:C:D:E with the presence of carotid plaques in RA patients.

Presentation Details:

Stepwise Development of a Multi-Protein Biomarker Index of Disease Activity (Presentation #345)
Y. Shen¹, N. Knowlton², M. Turner³, C. Sutton⁴, D. Smith⁴, D. Chernoff¹, L. Hesterberg¹, R. Roubenoff⁵, N.A. Shadick⁶, M. Weinblatt⁶, G. Cavet¹ and M. Centola³, ¹Crescendo Bioscience, So. San Francisco, CA, ²NSK Statistical Solns, LLC, Oklahoma City, OK, ³OMRF, Oklahoma City, OK, ⁴Crescendo Bioscience, Oklahoma City, OK, ⁵Biogen-Idec, Cambridge, MA, ⁶Brigham & Women's Hosp, Boston, MA

The Apolipoprotein Complex LpAII:B:C:D:E Is Increased in Rheumatoid Arthritis and Is Associated with Carotid Atherosclerosis (Presentation #602)
Petar Alaupovic¹, Jon T. Giles², Nicholas Knowlton³, Adam Payne¹, G. Cavet⁴, Michael Centola³ and Joan M. Bathon², ¹Oklahoma Medical Research Foun, Oklahoma City, OK, ²Johns Hopkins University, School of Medicine, Baltimore, MD, ³Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁴Crescendo Bioscience, Inc., South San Francisco, CA

Predicting Radiographic Progression in Rheumatoid Arthritis with Ultrasound and Biomarkers (Presentation #1464)
G. Cavet¹, Y. Shen¹, S. Abraham², D. Chernoff¹, M. Centola³ and P. Taylor², ¹Crescendo Bioscience, Inc., South San Francisco, CA, ²Imperial College London, London, United Kingdom, ³OMRF, Oklahoma City, OK

Disease Activity Test Update
Vectra™ DA (Disease Activity Test) is a multi-protein biomarker test intended to aid in the assessment of disease activity in RA patients when used in conjunction with standard clinical assessment. Vectra DA is being processed in Crescendo Bioscience’s CLIA-certified laboratory, located in South San Francisco, CA.