Multibiomarker disease activity test 'stronger predictor' of radiographic progression in RA
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The adjusted multibiomarker disease activity test for rheumatoid arthritis is prognostic for radio progression, and is a stronger predictor than conventional risk factors, according to data published in Arthritis Research & Therapy.
“The multibiomarker disease activity (MBDA) blood test measures 12 serum biomarkers, including CRP, to generate a score on a scale of 1-100 that represents the level of disease activity in adult patients with RA,” Jeffrey R. Curtis, MD, MS, MPH, of the University of Alabama at Birmingham, and colleagues wrote. “The MBDA score has categories of low (<30), moderate (30-44), and high (>44) disease activity. Change in MBDA score correlates with change in clinical disease activity.”
“When assessing change from a moderate or high MBDA score to a later score, the minimally important difference is 8 points,” they added. “In 2019, the MBDA score was the subject of a systematic review and meta-analysis, and the American College of Rheumatology disease activity measures working group concluded that the MBDA score was one of 11 RA disease activity measures that fulfilled the minimum standard for regular use.”
According to Curtis and colleagues, a newer version of the MBDA score, adjusted for age, sex, and adiposity, has been validated in two cohorts — OPERA and BRASS — for predicting the risk for radiographic progression in RA. To extend these findings and further validate the adjusted MBDA score as a predictor of radiographic progression risk, as well as compare it to other risk factors, the researchers analyzed a total of four cohorts. These included the previous BRASS and OPERA cohorts in addition to the Leiden registry and the SWEFOT study. In all, the cohorts include 953 patients receiving non-biologic and biologic disease-modifying antirheumatic drugs.
Curtis and colleagues used linear and logistic regression to examine the associations of annual radiographic progress with the adjusted MBDA score, as well as with seropositivity and clinical measures. Specifically, the researchers validated the adjusted MBDA score in the Leiden and SWEFOT cohorts, and compared the score against other measures in all four cohorts. They then used the adjusted MBDA score to develop curves for predicting risk for radio progression.
According to the researchers, both univariable and bivariable analyses validated the adjusted MBDA score and found it to be “the strongest, independent predicator of radiographic progression,” compared with seropositivity, baseline radiographic progression, DAS28-CRP, CRP swollen joint count, or the Clinical Disease Activity Index (CDAI). In addition, neither the DAS28-CRP, CDAI, swollen joint count, nor CRP measures added significant information to the adjusted MBDA score as a predictor, while the frequency of radiographic progression agreed with the adjusted MBDA score even when it was discordant with the other measures.
The researchers also found that the rate of progression increased from less than2% in the low adjusted MBDA category to 16% in the high category. Additionally, a modeled risk curve demonstrated that risk increased continuously, topping 40% for the highest adjusted MBDA scores.
“We have validated the adjusted MBDA score and performed the largest combined analysis to date of it as a prognostic test for radiographic progression in RA,” Curtis and colleagues wrote. “The adjusted MBDA score was a stronger predictor of radiographic progression than DAS28-CRP, CRP, SJC, and CDAI, and its prognostic ability was not improved by any of these other measures, including when it was discordant with them.”
“A risk curve was generated to show that the risk of rapid radiographic progression approached zero when the adjusted MBDA score was low, and it increased continuously with the adjusted MBDA score, such that risk exceeded 40% and included the most severe cases of progression when the adjusted MBDA score was very high,” they added. “The results of this study validate the adjusted MBDA score as an objective, independent measure of disease activity that, without requiring information from clinical assessment, can stratify RA patients according to their risk for developing new joint damage.”
Perspective
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Prior to the biologic era, up to 50% of patients with rheumatoid arthritis were disabled at 10 years. This statistic should emphasize the importance of preventing disability in our patients with rheumatoid arthritis. Early in the disease it is inflammation that drives disability; however, after several years, radiographic progression becomes the driver of disability.
Since the launch of the biologic disease-modifying antirheumatic drugs in 1999, and then the targeted synthetic DMARDs, the rheumatology community has demanded that our therapeutic agents retard radiographic progression as a surrogate for disability. We, therefore, need an objective way to predict which patients are at highest risk for joint damage and subsequent disability. From a management standpoint, this group should be followed more closely and treated more aggressively.
Earlier studies have demonstrated that the MBDA score is a strong predictor of radiographic damage. More recently, the MBDA score has been reported with a result adjusted for the effects of age, sex, and adiposity (measured as serum leptin concentration). This adjusted MBDA score was shown to be an even better predictor of the risk of radiographic damage in a previously reported study.
The present study was performed to further validate the adjusted MBDA score as a predictor of radiographic progression. It included four cohorts – with two early disease and two established disease – analyzed to determine the ability of the adjusted MBDA score to predict radiographic progression. Radiographic progression was found to be more frequent and more severe in patients with higher adjusted MBDA scores, though not quite as absolute as reflected in earlier data.
In patients with low disease activity as measured by the adjusted MBDA score there was almost no radiographic progression. The risk of progression increased continuously as the MBDA score increased and exceeded 40% for patients with the highest adjusted MBDA scores. From a therapeutic viewpoint this would suggest that, if a patient has a low adjusted MBDA score, their current treatment should prevent radiographic progression. However, if the patient’s adjusted MBDA score is high, a change in treatment might be needed to prevent radiographic progression and subsequent disability.
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