Background/Purpose: Previous studies have demonstrated the efficacy of a treat-to-target approach to optimize therapeutic outcomes for patients with RA using measures of clinical disease activity to monitor patient response. The Multi‐Biomarker Disease Activity (MBDA) test is an objective molecular measure of 12 serum biomarkers that has been validated as a measure of disease activity and predictor of radiographic progression. A recent study has also demonstrated that adjusting the MBDA score for age, sex and adiposity improves its ability to predict radiographic progression relative to the unadjusted MBDA score and clinical measures of disease activity (i.e. DAS28). Short-term variation in test biomarkers can be observed as day-to-day (daily) or within-day (diurnal) fluctuations. Establishing a minimally important difference (MID) in the MBDA score – the smallest score change that exceeds inherent variability – accounts for such fluctuations and provides a reference point for interpreting MBDA score changes over time. This study evaluated daily and diurnal variation in MBDA scores adjusted for age, sex and adiposity. The data were used to determine the MID and establish a cut point for meaningful change in the MBDA score.

Methods: 28 adult, seropositive RA patients with clinically stable disease were enrolled from a single US rheumatology research center. MBDA testing was performed for each patient on 9 non-fasting serum samples obtained over 4 consecutive days: 6 samples during the first 24 hours (8 AM, 12 PM, 4 PM, 8 PM, 12 AM, and 8 AM), 1 sample at 12 PM in the next 24-hour period, 1 sample at 8 AM on each of the two following days. Patients were stratified by MBDA disease activity category (high, >44; moderate, 30-44; low, <30). MBDA scores were also adjusted for age, sex and adiposity, using serum leptin as a proxy for adiposity.

MBDA score variation was assessed for daily and diurnal timeframes. The standard deviation (SD) of MBDA scores was calculated using a linear mixed model that included random effects for patient, day, and time of day. The MID was calculated as z_0.95 √(2 x total variance of MBDA scores), where z_0.95 is the standard normal deviate corresponding to the 95^th percentile. The MID was assessed for the unadjusted and adjusted MBDA scores for all patients as well as for those with clinically active disease (moderate/high).

Results: In a combined daily-diurnal variation analysis including all patients, the SD of MBDA score change was 4.7, and the MID was 11. In a subset analysis of moderate/high disease activity categories (n=22), the total SD of MBDA scores was 3.6, and the MID was 8 MBDA units. When the MBDA was adjusted for age, sex and adiposity, the MID for patients with moderate/high disease activity was unchanged at 8 units.

Conclusion: For individuals with moderate or high disease activity based on the adjusted or unadjusted MBDA score, the MID was determined to be 8 MBDA score units. A change in MBDA score greater than or equal to the MID represents a change in RA disease activity that clinicians can use as a benchmark for therapeutic drug efficacy and can be incorporated in a treat-to-target strategy that combines both clinical and molecular metrics.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/determination-of-the-minimally-important-difference-for-interpreting-the-ra-multi-biomarker-disease-activity-test-score-impact-of-diurnal-and-daily-biomarker-variation-on-scores-adjusted-for-age-sex/