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Abstract
Background The Multi-Biomarker Disease Activity (MBDA) score has been validated as a disease activity metric in rheumatoid arthritis (RA) patients. Patients initiating new therapy or changing therapy frequently have moderate to high MBDA scores. Understanding short term biological variation of MBDA scores in these patients is important in order to determine a minimally important difference (MID).
Objectives To evaluate biological variation in MBDA scores over a 24-hour period and from day to day in patients with clinically stable RA with moderate to high MBDA scores at baseline and to determine the MID in these patients.
Methods We performed an analysis of 22 RA patients with moderate or high baseline MBDA scores. Adults with clinically stable seropositive RA (>8 weeks without DMARD and/or biologic medication changes and ≤10 mg prednisone per day) who had MBDA scores of moderate (MBDA 30–44) or high (MBDA >44) were eligible. Serum samples were obtained 5 times over the first 24-hour period (8 AM, 12 PM, 4 PM, 8 PM, and 8 AM); at 12 PM in the next 24-hour period; and at 8 AM the next 2 consecutive days, for a total of 8 timepoints. An additional midnight sample was excluded from the analysis because this timepoint is not relevant to normal clinical practice hours. Diurnal variation was calculated using 5 timepoints over the first 24 hours. Daily variation was determined using 4 timepoints taken at 8 AM on successive days. Combined diurnal and daily variation was calculated using 8 timepoints over 4 days. For each patient, absolute changes in MBDA scores were calculated for all possible pairs of timepoints for: a) diurnal variation (total 220 pairs), b) daily variation (total 132 pairs) and c) diurnal and daily variation (total 616 pairs). MID was calculated as the 90th percentile of absolute changes using all diurnal and daily variation data. Bootstrapping was used to validate the result.
Results Of patients included in the analysis, 13 had moderate MBDA scores and 9 had high MBDA scores at baseline. Baseline demographics were: 73% women, mean age 61.8 (SD: 12.1) years, mean MBDA score 43.9 (SD: 8.3), and mean CDAI 20.2 (SD: 17.1). No patients were on glucocorticoids. Based on the analysis of the absolute change of MBDA score in the data with daily and diurnal variation combined, the mean was 3.4 (SD: 3.8), the median (Q1, Q3) was 2 (1, 5), and the MID was calculated as 7. Similar results were obtained using a bootstrap method. Minimal variability in mean MBDA scores was observed over 4 days for patients with moderate and high baseline MBDA scores (Figure 1).
Conclusions Based upon the short term biologic variability of moderate and high MBDA scores, the MID was 7 units. An absolute change exceeding this threshold is unlikely due to diurnal and daily biological variation of the MBDA scores.
Disclosure of Interest D. Chernoff Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., R. Bolce Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., C. Hwang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., X. Wang Shareholder of: Myriad Genetics, Inc., Employee of: Crescendo Bioscience Inc., A. Kivitz Consultant for: Genentech, Pfizer, UCB, Janssen, J. Curtis Grant/research support from: Crescendo Bioscience Inc., Consultant for: Crescendo Bioscience Inc.