title: Interpreting the multi-biomarker disease activity score in the context of tocilizumab treatment for patients with rheumatoid arthritis.
abstract: The multi-biomarker disease activity (MBDA) score measures 12 proteins involved in the pathophysiology of rheumatoid arthritis (RA) to assess disease activity (DA). Previous studies demonstrated correlations between MBDA and clinical DA scores with some RA therapies. In this analysis, the relationship between DA and MBDA scores and changes in MBDA component biomarkers were evaluated in tocilizumab (TCZ)-treated patients. Patients from the ACT-RAY study were included in this analysis if they had DA measures and serum collected at pre-specified time points with sufficient serum for MBDA testing at ≥1 visit. Descriptive statistics, associations between outcomes, and percentage agreement between DA categories were calculated. Seventy-eight patients were included and were similar to the ACT-RAY population. Correlations between MBDA score and DAS28-CRP were ρ = 0.50 at baseline and ρ = 0.26 at week 24. Agreement between low/moderate/high categories of MBDA score and DAS28-CRP was observed for 77.1 % of patients at baseline and 23.7 % at week 24. Mean changes from baseline to weeks 4, 12, and 24 were proportionately smaller for MBDA score than DAS28-CRP. Unlike some other MBDA biomarkers, interleukin-6 (IL-6) concentrations increased in most patients during TCZ treatment. Correlations and agreement between MBDA and DAS28-CRP or CDAI scores were lower at week 24 versus baseline. The proportionately smaller magnitude of response observed for MBDA score versus DAS28-CRP may be due to the influence of the increase in IL-6 concentrations on MBDA score. Thus, MBDA scores obtained during TCZ treatment should be interpreted cautiously and in the context of available clinical information.
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA. bill.reiss@roche.com.
authors.forename: William G
authors.initials: WG
authors.lastname: Reiss
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
authors.forename: Jenny N
authors.initials: JN
authors.lastname: Devenport
authors.affiliation: Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Low
authors.affiliation: Crescendo Bioscience, Inc., South San Francisco, CA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Wu
authors.affiliation: Crescendo Bioscience, Inc., South San Francisco, CA, USA.
authors.forename: Eric H
authors.initials: EH
authors.lastname: Sasso
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D011237:Predictive Value of Tests; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015415:Biomarkers; D001798:Blood Proteins; D018836:Inflammation Mediators; C502936:tocilizumab; D008727:Methotrexate
keywords: Biomarker; C-reactive protein (CRP); Interleukin-6 (IL-6); MBDA; Rheumatoid arthritis; Tocilizumab