A group of biomarkers that reflect the various underlying disease processes in rheumatoid arthritis correlates well with conventional disease activity scores and may prove useful in predicting treatment response, researchers found.

The multiple biomarker test score was significantly associated with the disease activity score in 28 joints (DAS28) in both seropositive and seronegative patients, with an area under the receiver operating curve (AUC) of 0.76 and a Pearson correlation coefficient of 0.57, according to Jeffrey R. Curtis, MD, of the University of Alabama at Birmingham, and colleagues.

Changes in the biomarker score from baseline also closely tracked DAS28 clinical response after 6 and 12 weeks of treatment, with an AUC of 0.77, the researchers reported online in Arthritis Care & Research.

The ability to more precisely measure disease activity in rheumatoid arthritis has gained in importance as outcomes have been shown to greatly improve with tight disease control and treat-to-target.

A number of measurement tools have been developed that incorporate symptoms and signs, patient-reported outcomes, and laboratory markers such C-reactive protein (CRP).

The DAS28 incorporating CRP is one such widely used index. Other assessment tools include the Clinical Disease Activity Index (CDAI) and the Simplified Disease Activity Index (SDAI).

However, outcomes measured by these assessment tools can be influenced by factors such as comorbidities, aging, and genetics.

In previous work, Curtis and colleagues constructed an algorithm that included 12 relevant biomarkers that might be used to complement the clinical assessment tools. The current study was intended to validate the biomarker score, which ranged from 1 to 100, in several cohorts.

The biomarker score in patients who were seropositive for either rheumatoid factor or anti-cyclic citrullinated peptide antibody was assessed in 230 patients from a North American longitudinal study known as InFoRM, in a cohort from the Brigham and Women's Hospital in Boston and a cohort from Leiden in the Netherlands.

The validity of the score to reflect disease activity also was assessed in 141 seronegative patients from the two U.S. cohorts.

The association between the biomarker score and response to therapy then was evaluated in a subgroup of the Boston cohort followed prospectively on treatment with methotrexate or a tumor necrosis factor inhibitor.

Patients were predominantly female, with a median age of 56. The spectrum of disease activity was wide, and the overall patient population was heterogeneous.

The ability of the marker score to classify patients as having low and high disease activity using the AUC was 0.77 for seropositive patients and 0.70 for seronegative patients, with Pearson correlations for the DAS28 of 0.56 and 0.43, respectively.

The marker score also correlated significantly with other disease assessment tools such as the CDAI, where the correlation for seropositive patients was 0.48 and for seronegative patients, 0.21.

In the subgroup where marker response to treatment was evaluated, significant decreases in the marker score were already apparent after 2 weeks and predicted later clinical response.

This finding was "intriguing," according to the researchers, and should be further evaluated to determine if the biomarkers could be used as an early means of determining treatment efficacy, "in both clinical trials and clinical practice."

The biomarkers chosen for inclusion reflected multiple aspects of the rheumatoid arthritis disease process. For instance, interleukin (IL)-6 and tumor necrosis factor are important in cytokine signaling, while matrix metalloproteinases are involved in cartilage remodeling, and CRP and serum amyloid A represent the acute phase response.

However, CRP is also an important component of the DAS28, so the researchers also sought to determine whether the biomarker score independently predicted DAS28 when CRP was removed from the analysis, and found that it did so in seropositive patients.

"The [multiple biomarker disease activity] score emphasizes the activity of underlying biological pathways rather than external signs and symptoms and should therefore provide information that is different from, and complementary to, clinical assessment," wrote Curtis and colleagues.

They called for further research to explore the use of the biomarker score in combination with imaging assessment to predict outcomes such as progression of joint damage.

Source: Biomarkers Track Arthritis Activity