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Determination of the minimally important difference (MID) in multi-biomarker disease activity (MBDA) test scores: impact of diurnal and daily biomarker variation patterns on MBDA scores

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Chernoff D1, Scott Eastman P2, Hwang CC2, Flake DD 2nd3, Wang X2, Kivitz A4, Curtis JR5. Clin Rheumatol. 2018 Aug 29. doi: 10.1007/s10067-018-4276-y. [Epub ahead of print]


Author information

1 Crescendo Bioscience Inc., 341 Oyster Point Blvd, South San Francisco, CA, USA. dchernoff@crescendobio.com.

2 Crescendo Bioscience Inc., 341 Oyster Point Blvd, South San Francisco, CA, USA.

3 Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT, USA.

4 Altoona Center for Clinical Research, 1125 Old Rte 220 N, Duncansville, PA, USA.

5 The University of Alabama at Birmingham, 510 20th Street S, Birmingham, AL, USA.


The Multi-Biomarker Disease Activity (MBDA) score is a validated rheumatoid arthritis (RA) disease activity measure based on 12 serum biomarkers. Here, we evaluate short-term biological variability of MBDA scores to determine the magnitude of change that might be considered clinically meaningful. Twenty-eight adult seropositive RA patients with clinically stable disease and no changes in RA medications for 4 weeks prior to study were enrolled. Nine serum samples were obtained over four consecutive days (non-fasting). MBDA score variation was assessed day-to-day (daily) and within 24 h (diurnal). The standard deviation (SD) of MBDA scores was calculated by a linear mixed model including random effects for patient, day, and time of day. The minimally important difference (MID) was calculated as [Formula: see text]. A subgroup analysis was performed for patients with active RA (moderate or high MBDA score). The SD of MBDA score change in the full cohort was 4.7 in a combined daily-diurnal variation analysis, which corresponds with an MID of 11. The SD of MBDA score change in the subset of patients with active RA (moderate/high MBDA scores) was 3.6. This corresponds with an MID of 8 units in patients with active RA for whom clinicians are most likely to need guidance with respect to therapeutic decisions. Changes in MBDA score ≥ 8 represent a change in RA disease activity that clinicians can use as a benchmark for therapeutic drug efficacy and can be incorporated into a treat-to-target strategy.