External validation of a multi-biomarker-based score for predicting risk of cardiovascular disease in patients with rheumatoid arthritis

Abstract

Background: A multi-biomarker disease activity (MBDA)-based cardiovascular disease (CVD) risk score was developed and internally validated in a Medicare cohort to predict 3-year risk for myocardial infarction (MI), stroke or CVD death in patients with rheumatoid arthritis (RA). It combines the MBDA score, leptin, MMP-3, TNF-R1, age and four clinical variables. We are now externally validating it in a younger RA cohort.

Methods: Claims data from a private aggregator were linked to MBDA test data to create a cohort of RA patients ≥18 years old. A univariable Cox proportional hazards regression model was fit using the MBDA-based CVD risk score as sole predictor of time-to-a-CVD event (hospitalized MI or stroke). Hazard ratio (HR) estimate was determined for all patients and for clinically relevant subgroups. A multivariable Cox model evaluated whether the MBDA-based CVD risk score adds predictive information to clinical data.

Results: 49,028 RA patients (340 CVD events) were studied. Mean age was 52.3 years; 18.3% were male. HR for predicting 3-year risk of a CVD event by the MBDA-based CVD risk score in the full cohort was 3.99 (95% CI: 3.51-4.49, p = 5.0×10-95). HR were also significant for subgroups based on age, comorbidities, disease activity, and drug use. In a multivariable model, the MBDA-based CVD risk score added significant information to hypertension, diabetes, tobacco use, history of CVD, age, sex and CRP (HR = 2.27, p = 1.7×10-7).

Conclusion: The MBDA-based CVD risk score has been externally validated in an RA cohort that is younger than and independent of the Medicare cohort that was used for development and internal validation.

Fig 1. Validation of MBDA-based CVD risk score for predicting CVD risk in subgroups.

Results show hazard ratios (HRs) with 95% confidence intervals. Subgroupings are based on information from baseline period, except Biologic initiation or change, which is based on treatment changes during follow-up. Vertical lines indicate HRs of 1.0 (solid line) and 3.99 (dashed line). All HRs are statistically significantly >1.0, except for the <40-year-old subgroup. Comparisons between complementary subgroups all have p >0.05 except for Hypertension (p = 0.046), Sex (p = 0.046), Baseline drug use (p = 0.012) and Age (p = 0.005), which are each non-significant after Bonferroni correction for 13 comparisons (i.e., p >0.0038 [0.05/13]). For baseline RA drugs, the Methotrexate (MTX) category includes combinations with conventional synthetic DMARDs (csDMARDs); the non-MTX csDMARD category excludes combinations with MTX, and the non-TNF inhibitor (TNFi) monotherapy (mono); and combination therapy (combo) categories include Janus kinase inhibitors.