Higher rheumatoid arthritis (RA) disease activity, as measured by a multi-biomarker disease activity (MBDA) panel, was associated with higher rates of hospitalized infections, myocardial infarction (MI), and coronary heart disease (CHD) events, analysis of Medicare data indicated.
Higher MBDA test scores were associated with increased serious infection events (HR 1.32 per 10-unit score increment, 95% CI 1.23-1.41), Jeffrey R. Curtis, MD, MPH, of the University of Alabama at Birmingham and colleagues reported.
Scores higher than 30 also were associated with increased MI (HR 1.52, 95% CI 0.92-2.49) and CHD rates (HR 1.54, 95% CI 1.01-2.34), compared with scores less than 30.
“In this large RA population predominantly consisting of older individuals, higher MBDA scores were associated with increased risk for hospitalized infection, MI and CHD events,” they wrote in Annals of the Rheumatic Diseases.
“A strong dose–response gradient existed between MBDA scores and hospitalized infections (pneumonia and sepsis). The patterns for MI and CHD events suggested more of a threshold effect, where those with the lowest level of disease activity and inflammation were at lowest risk, but gradations with higher levels of the biomarker were relatively absent,” they added.
The 100-point MBDA system is based on a set of 12 protein biomarkers, shown to correlate well with disease activity in several RA cohorts. It is commercially available from Crescendo Biosciences under the name Vectra DA. A score under 30 is considered low, 30–44 moderate, and over 44 high.
For this analysis, the researchers used national Medicare fee-for-service claims from 2010 to 2014, linking that information to patient-specific MBDA scores supplied by Crescendo.
To be included in the study, a patient needed to have at least one valid MBDA score linked to Medicare claims and at least 365 continuous days of Medicare with Part D coverage before the first valid MBDA test date.
The researchers excluded patients who had an International Classification of Diseases (ICD)-9 diagnosis code for ankylosing spondylitis, inflammatory bowel disease psoriasis, psoriatic arthritis, systemic lupus erythematosus, malignancy (except non-melanoma skin cancer), polymyalgia rheumatica, and giant cell arteritis in the 12-month baseline period. They also excluded patients who had initiated any non-tumor necrosis factor biologic or synthetic targeted disease-modifying anti-rheumatic drugs (DMARDs) in the 183 days before the index date.
Patients who had a prior MI, coronary artery bypass grafting, or percutaneous coronary intervention were not included in the MI and CHD outcome.
Because MBDA scores could be affected by an evolving outpatient infection or MI, the researchers also excluded patients from the MI and CHD analysis if they had heart attacks or coronary events in the 7 days following the MBDA test. Similarly, they excluded patients from the serious infection outcome if they had a serious infection in the 14 days after the test.
A total of 17,433 patients were eligible for the serious infection analysis and 16,796 patients for the MI and CHD outcome. Overall, the average age was 69 years; 79% were women, 81% were white, and 38% were disabled. These patients used methotrexate (54%), oral glucocorticoids (53%), non-biologic DMARDs (40%) and biologics (17%) to treat their RA.
Characteristics of patients in lower MBDA categories suggested they were younger (a 3-year difference), had a lower burden of comorbidities, and used less glucocorticoids and more biologics than patients with higher MBDA scores.
After multivariable adjustment, higher MBDA scores were associated with statistically significantly higher rates of serious infection events and higher MI and CHD rates.
Because C-reactive protein, one of the MBDA biomarkers, might influence outcomes, the researchers performed sensitivity analyses excluding it and found similar results: a 1.5-fold (CHD) and 1.7-fold (MI) elevated risk for patients in the higher disease activity category compared with the lowest.
“The current study is novel in that it leveraged a large administrative data source linked to a laboratory test provider database to address a question that neither data source by itself could address,” the authors wrote.
The results should be interpreted in light of the study design, they noted. It included predominantly older adults and findings might not apply to younger RA patients.
“However, given that the prevalence of infectious and CHD risk factors generally increases with age, we would speculate that the associations between RA disease activity and the outcomes that we studied might be even stronger in younger patients with RA,” they wrote.
This analysis was supported in part by Crescendo Bioscience, which is part of Myriad Genetics.
Curtis is a consultant for Myriad Genetics and has received research grants from them.
Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner