Biomarker Panel an Objective Measure of Disease Activity, Treatment Response in Rheumatoid Arthritis

VBCR - December 2012, Volume 1, No 6 - Personalized Medicine in Rheumatology

By Wayne Kuznar

Washington, DC—A panel of disease biomarkers can measure changes in disease activity in response to a range of therapies for rheumatoid arthritis (RA), researchers announced at the 2012 meeting of the American College of Rheumatology (ACR).

Using a score derived from a panel of biomarkers known as Vectra DA, several studies confirmed changes in disease activity in response to the traditional disease-modifying therapy abatacept (Orencia) and interleukin (IL)-6 inhibition.

The biomarker panel integrates 12 serum biomarkers associated with RA disease severity (Figure) into a single objective score, which may be used to inform treatment decisions.

The 12 biomarkers in the panel include:

  • 1 adhesion molecule: vascular cell adhesion molecule-1
  • 2 growth factors: epidermal growth factor and vascular endothelial growth factor-A
  • 2 cytokine receptors: IL-6 and tumor necrosis factor receptor type 1
  • 2 matrix metalloproteinases: matrix metalloproteinase-1 (or collagenase-­1) and matrix metalloproteinase-3 (or stromelysin-1)
  • 1 skeletal-related protein: chitinase 3–like protein
  • 2 hormones: leptin and resistin
  • 2 acute-phase proteins: serum amyloid A and C-reactive protein (CRP).

The Data
A team of Japanese investigators from the University of Occupational and Environmental Health, Kitakyu­shu, Japan, conducted separate studies of the biomarker panel in patients with RA who received the IL-6 inhibitor tocilizumab (Actemra) or the Janus kinase inhibitor tofacitinib (Xeljanz).

In one study, 52 patients with RA received tocilizumab for at least 1 year; their biomarker disease activity score (DAS) was measured at baseline and again at week 52. A significant correlation was seen between the biomarker score and the score on the DAS 28-joint (DAS28)-erythrocyte sedimentation rate (ESR), DAS28-CRP, Clinical Disease Activity Index, and the Simplified Disease Activity Index (SDAI), as well as the health assessment questionnaire and the Modified Total Sharp Score (mTSS) that indicates structural damage.

The biomarker score was able to differentiate between clinical remission and nonremission, as defined by other criteria, including the ACR/European League Against Rheumatism definition. The biomarker score reflected disease activity and tracked therapeutic effects; furthermore, remission, as defined by the biomarker score, was preferable to DAS28 for predicting good outcome in radiographic damage and in physical function.

Using the biomarker score, 37 patients who received tofacitinib for 28 to 40 weeks in phase 2 or phase 3 clinical trials were evaluated. Clinical remission defined by a biomarker score of ≤25 was seen in 40.5% of the patients, compared with 37.8% of patients based on the SDAI and 35.1% by the DAS28-ESR. The mean IL-6 levels decreased markedly at 1 year; 78% of the patients who achieved an IL-6 concentration ≤9 pg/mL had progression of mTSS by ≤0.5 compared with only 38% of the patients with IL-6 concentrations >9 pg/mL.

 

A Molecular Gold Standard
“We have developed a molecular gold standard that is the equivalent of a carefully done examination, but now it is done in the blood where there is no subjectivity,” said David N. Chernoff, MD, Senior Vice President of Medical Affairs, Crescendo Bioscience, the developer of Vectra DA. “We feel it has some advantages over standard measures of disease activity.”

In a study conducted by researchers from Crescendo Bioscience, significant correlations were observed between the DAS28-CRP and the multibiomarker disease activity (MBDA) score in 50 patients with RA who received abatacept plus methotrexate (Trexall) to placebo. Those randomized to abatacept plus methotrexate had significantly greater improvements in the MBDA score and the DAS28-CRP versus those receiving placebo. The MBDA score also correlated with synovitis and osteitis scores.

The panel of biomarkers also responded quickly to combination therapy using methotrexate and prednisone and correlated with the DAS28-ESR in a 104-patient study.

“Doctors have used low-dose prednisone in patients with RA for a very long time. It has very rapid effects, it makes people feel better, but no one really knows if it is appropriate to use steroids routinely in patients with RA,” Dr Chernoff said. “For the first time we are seeing why steroids have such a profound effect on disease activity and better x-ray outcomes. You can see it in the composite panel and the individual biomarkers. Molecular profiling is the new dawn of rheumatology.”

Related Items
MBDA May Predict Post-TNFi Flares in Patients with Rheumatoid Arthritis
Rosemary Frei, MSc
VBCR - December 2015, Volume 4, No 6 published on December 15, 2015 in Personalized Medicine in Rheumatology
RA Disease Marker Proving to Be Versatile
Rosemary Frei, MSc
VBCR - December 2015, Volume 4, No 6 published on December 15, 2015 in Personalized Medicine in Rheumatology
MBDA May Predict RA Relapses During DMARD Tapering
Rosemary Frei, MSc
VBCR - December 2015, Volume 4, No 6 published on December 15, 2015 in Personalized Medicine in Rheumatology
Autoantibodies in Patients with RA Could Lead to More Precise Diagnosis, Therapy
E. K. Charles
VBCR - October 2014, Volume 3, No 5 published on October 30, 2014 in Personalized Medicine in Rheumatology
Advances in Genotyping Pinpoints to Genetic Determinant
Phoebe Starr
VBCR - August 2014, Volume 3, No 4 published on September 12, 2014 in Personalized Medicine in Rheumatology
Gene Expression Profiling Shows Potential in Personalized Medicine for RA
E. K. Charles
VBCR - June 2014, Volume 3, No 3 published on July 1, 2014 in Personalized Medicine in Rheumatology
Novel Plasma Cell Signature May Be Useful in a Range of Rheumatic Disorders
Alice Goodman
VBCR - April 2014, Volume 3, No 2 published on April 23, 2014 in Personalized Medicine in Rheumatology
New RA Susceptibility Locus Identified
Alice Goodman
VBCR - April 2014, Volume 3, No 2 published on April 23, 2014 in Personalized Medicine in Rheumatology
Future Therapies May Come from Modulation of Cell Signaling in Rheumatic Disease
Phoebe Starr
VBCR - February 2014, Volume 3, No 1 published on February 21, 2014 in Personalized Medicine in Rheumatology
Osteoarthritis Biomarker Field Fraught with Challenges
VBCR - December 2013, Volume 2, No 6 published on December 30, 2013 in Personalized Medicine in Rheumatology
Last modified: May 21, 2015
  • Rheumatology Practice Management
  • American Health & Drug Benefits
  • Value-Based Cancer Care
  • Value-Based Care in Myeloma
  • Value-Based Care in Neurology