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Predicting risk for radiographic damage in rheumatoid arthritis: comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Author

Curtis JR1, Brahe CH2,3, Østergaard M2,3, Lund Hetland M2,3, Hambardzumyan K4, Saevarsdottir S4,5, Wang X6, Flake Ii DD7, Sasso EH6, Huizinga TW8. Curr Med Res Opin. 2019 Mar 14:1-11. doi: 10.1080/03007995.2019.1585064. [Epub ahead of print]

Author Information

1 University of Alabama at Birmingham , Birmingham , AL , USA. 

2 Copenhagen Center for Arthritis Research and DANBIO , Center for Rheumatology and Spine Diseases , Glostrup , Denmark.

3 Department of Clinical Medicine , University of Copenhagen , Copenhagen , Denmark.

4 Rheumatology Unit, Department of Medicine , Solna, Karolinska Institutet , Stockholm , Sweden.

5 Institute of Environmental Medicine , Karolinska Institutet , Stockholm , Sweden.

6 Crescendo Bioscience Inc. , South San Francisco , CA , USA.

7 Myriad Genetics Inc. , Salt Lake City , UT , USA.

8 Leiden University Medical Center , Leiden , Netherlands.

Abstract

OBJECTIVE: 

To compare the multi-biomarker disease activity (MBDA) score with the DAS28-CRP and CRP for predicting risk of radiographic progression in patients with rheumatoid arthritis.

METHODS: 

Published studies of the MBDA score and radiographic progression with ≥100 patients per cohort were evaluated. Rates of radiographic progression over 1 year were determined across the low/moderate/high categories for MBDA score (low/moderate/high: <30, 30-44, >44), DAS28-CRP (low/moderate/high: ≤2.67, >2.67-4.09, >4.09) and CRP (low/moderate/high: ≤10, >10-30, >30 mg/L), with positive and negative predictive value (PPV, NPV) and relative risk (RR) determined for high vs. not-high (i.e. low and moderate combined) categories. Patient-level data from studies having all three measures was pooled to: (1) determine a combined RR for radiographic progression in the high vs. not-high categories for each measure; and (2) compare the predictive ability of MBDA score vs. DAS28-CRP by comparing the rates of radiographic progression observed in subgroups created by cross-classifying the high and not-high categories of each measure.

RESULTS: 

Five cohorts were identified for inclusion (total N=929). In each, radiographic progression was more frequent with increasing MBDA scores. Among the three cohorts with requisite data, PPVs were generally similar using categories of MBDA score, DAS28-CRP or CRP but NPVs were greater for MBDA score (93-97%) than DAS28-CRP or CRP (77-87%). RRs for radiographic progression were greater when based on categories of MBDA score than DAS28-CRP or CRP and the combined RR was greater for MBDA score (4.6, p < .0001) than DAS28-CRP (1.7, p = .02) or CRP (1.7, p = .002). For patients cross-classified by MBDA score and DAS28-CRP, high vs. not-high MBDA score significantly predicted radiographic progression independently of DAS28-CRP.

CONCLUSIONS: 

High and not-high MBDA scores were associated with increased and low risk, respectively, for radiographic progression over one year. MBDA score was a better predictor of radiographic progression than DAS28-CRP or CRP.