Multi-Biomarker Disease Activity Scores Should be Interpreted With Caution

In a clinical trial of the effectiveness of repository corticotropin injection (RCI) treatment in patients with persistently active rheumatoid arthritis (RA), the 28-joint Disease Activity Score using erythrocyte sedimentation rate (DAS28-ESR) and Clinical Disease Activity Index (CDAI) indicated improvements in disease activity; similar improvements were not observed using multi-biomarker disease activity (MBDA) scores, according to study findings published in Arthritis Care & Research.

The DAS28-ESR and CDAI are 2 tools that have been validated for evaluating RA disease activity. The MBDA is also used to measure RA disease activity, however, it is based on biochemical markers and excludes the subjective measurements of swollen and tender joints and patient assessments found in the DAS28-ESR and CDAI. This study assessed the effectiveness of MBDA scores, compared with the DAS28-ESR and CDAI, in measuring RA disease activity in patients enrolled in a clinical trial of RCI, a short-term adjunctive treatment for patients with active RA.

This was a multicenter, randomized controlled trial (ClinicalTrials.gov Identifier: NCT02919761). Participants were aged 18 years and older with persistently active RA who were undergoing glucocorticoid and DMARD treatment. During the open-label treatment period, patients received 80 U RCI for 12 weeks. Those who achieved low disease activity continued to the double-blind treatment period and were randomly assigned (1:1 ratio) to continue receiving RCI or placebo for an additional 12 weeks. Disease activity was measured using the DAS28-ESR, CDAI, and MBDA score. The primary and secondary endpoints were low disease activity at weeks 12 and 24, respectively.        

A total of 259 patients were enrolled in the trial. During the open-label phase, the percentage of patients with low disease activity as measured by the DAS28-ESR and CDAI increased from 0% and 0.4%, respectively, at baseline to 62.9% and 65.3%, respectively, at 12 weeks (both P <.0001). Changes in MBDA scores were smaller (15.8% at baseline and 21.2% at 12 weeks) but significant (P <.0001). During the double-blind phase, the DAS28-ESR and CDAI noted a greater loss in the percentage of patients with low disease activity in the placebo group vs the RCI treatment group; this change was not seen when MDBA scores were used to measure disease activity. Correlation of total and composite MDBA scores with the DAS28-ESR and CDAI were largely weak (r ≤.3) to moderate (r >.3 but <.5).

Limitations to the study were cited as possible selection bias and that confounding factors were not able to be accounted for.

“Our results are consistent with the recent [American College of Rheumatology (ACR)] guidance recommending the DAS28-ESR and CDAI to measure disease activity in clinical practice,” the researchers concluded. “The reasons underlying our study’s finding that the MBDA was not reliably responsive to changes in RA disease activity with multiple therapies are unclear.” They suggested that possibly, “the specific biomarkers included in the MBDA score, although related to the pathogenesis of RA, may not be directly related to clinically meaningful disease activity. The use of biomarker components of the MBDA to guide therapy is tempting but requires further investigation.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Fleischmann R, Liu J, Zhu J, Segurado OG, Furst DE. Discrepancy between multi-biomarker disease activity and clinical disease activity scores in patients with persistently active rheumatoid arthritis. Arthritis Care Res. Published online February 28, 2021. doi:10.1002/acr.24583