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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

Author information

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]

Abstract

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.

Abstract

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.