Current guidance on rheumatoid arthritis (RA) stresses the importance of considering comorbidity when assessing disease activity and making clinical decisions.1 Comorbidities commonly associated with RA include cardiovascular disease (CVD), lung disease and malignancy.2
The complex relationship between RA and CVD comorbidities
The presence of CVD itself has been shown to increase the risk of death in RA patients by approximately 50%,3 and there is an emerging relationship between RA, CVD and the therapies used to treat them.
The use of RA treatments such as tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) may be associated with a reduced risk of the occurrence of cardiovascular events in patients with rheumatoid arthritis.4 Conversely, anti-inflammatory drugs used in RA such as corticosteroids and nonsteroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events.4 There is also evidence to show the treatment of cardiovascular comorbidities with statins can potentially ameliorate RA disease activity and lower inflammatory biomarkers.5 Further research evaluating the interplay between CVD and RA, in addition to the impact of concomitant CVD on treatment and clinical outcomes in patients with RA, is required.
However, the stringent eligibility criteria used in randomized controlled trials do not often allow recruitment of a broader real-world spectrum of RA patients – patients recruited are usually younger than 60 years old and may not suffer significant clinical comorbidity. In practice, one third of RA patients are over the age of 65,6 and comorbidities are common.2
Biomarkers to improve clinical trials for patients with RA and CVD comorbidities
Innovative and tailored clinical trial designs incorporating novel biomarkers in RA can facilitate identification of different groups of patients who may be more likely to respond to a particular therapy or who are at risk of imminent relapse needing therapeutic intervention. They could help to monitor disease progression and risk status throughout the study. Such biomarkers can potentially support an earlier readout in terms of potential efficacy (and safety) and may help predict the longer term clinical RA outcome measures, ultimately informing better clinical practice. GlycA, Labcorp’s unique inflammatory biomarker, can be used to identify and monitor systemic levels of inflammation during anti-inflammatory drug therapy. GlycA is the name given by Labcorp to the nuclear magnetic resonance (NMR) signal that originates from glycosylated acute phase proteins. This biomarker is of particular interest as GlycA levels are higher in patients with RA and are associated with coronary artery disease in these patients. These observations suggest that GlycA may also be a useful biomarker of CVD risk in RA patients as compared with conventional CVD biomarkers such as low-density lipoprotein (LDL) cholesterol and high-sensitivity C-reactive protein (hs-CRP)
Covance is committed to advancing RA clinical trials in partnerships that will further the understanding and improvement of treatments in RA. To learn more about how we can help your trial, please click here for our inflammation drug development solutions.
- Smolen JS and Steiner G. Nat Rev Drug Discov 2003; 2:473–488
- van Onna M and Boonen A. BMC Musculoskeletal Disorders 2016; 17:184
- Aviña-Zubieta JA, et al. Arthritis Rheum 2008; 59:1690–1697
- Roubille C, et al. Ann Rheum Dis 2015; 74:480–489
- McCarey DW, et al. Lancet 2004; 363:2015–2021
- Ranganath VK, et al. Rheumatology (Oxford) 2013; 52:1809–1817