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Abstract
Background Patients (pts) with rheumatoid arthritis (RA) are at-risk for cardiovascular (CV) disease, even when accounting for traditional risk factors (eg, hypertension, dyslipidemia). This increased risk is usually attributed to high levels of inflammation. Despite improved therapies that limit inflammation, RA pts remain at-risk; distinguishing those most at-risk remains challenging.
Objectives To investigate structural damage as a predictor for CV risk in RA pts in 2 long-term trial populations.
Methods Data originate from 2 large, phase 3, randomized, controlled trials of adalimumab, in which pts were followed for up to 10 years (yrs): DE019, which included MTX-inadequate responders with established RA treated for 1 yr in a double-blind (DB) period followed by a 9-yr open-label (OL) period, and DE013, which included MTX-naïve pts with early RA treated for 2 yrs in a DB period followed by an 8-yr OL period. In this analysis, CV events of interest included: acute coronary syndrome, cardiac arrest, coronary artery insufficiency, myocardial infarction, myocardial ischaemia, carotid artery occlusion, cerebellar infarction, cerebrovascular accident, cerebral infarction, cerebral haemorrhage, embolic stroke, hemiparesis, lacunar infarction, cerebral ischaemia, ischaemic cerebral infarction, ischaemic stroke, troponin increased, and death. Age, sex, RA duration, baseline (bl) modified total Sharp score (mTSS), rheumatoid factor (RF) status, and time-averaged(TA)-DAS28(CRP) were summarized and included in a proportional hazard model to assess significant association with time-to-first CV event in both DE019 and DE013.
Results During DE019, 36/619 pts experienced a total of 42 documented CV events. On average, pts with a CV event were older at bl (mean age=63 vs 56 yrs), had a longer RA duration (mean =15.0 vs 10.7 yrs), and had more structural damage (mean mTSS =91.5 vs 65.9 units). Because RA disease duration was highly correlated with bl mTSS (P <0.001), only bl mTSS was included in the final model. In pts with established RA, age and bl mTSS were both significantly associated with time-to-first CV event (Table). During DE013, there were 32 CV events experienced by 23/799 pts. Pts experiencing a CV event were older than those without (mean =63 vs 52 yrs), but mean RA duration (mean =0.8 yrs in both) and bl mTSS (mean mTSS =22.9 vs 19.3 units) were comparable between groups. In a model that included the same variables, only age and sex were found to be significantly associated with time-to-first CV event. Of note, TA-DAS28(CRP) was not associated with time-to-first CV event in either study.
Conclusions Higher bl mTSS was significantly associated with increased CV risk in pts with established RA, but not in pts with early RA. These data underscore the need to identify radiographic progressors early in their disease for more intensive treatment, as increased RA disease burden may also translate into increased risk for a serious CV event.
Acknowledgements AbbVie Inc. sponsored the studies (DE019: NCT00195702; DE013: NCT00195663), contributed to their design, and participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. Medical writing support was provided by Benjamin Wolfe, PhD, of AbbVie Inc.
Disclosure of Interest R. Landewé Consultant for: AbbVie Inc., Amgen, BMS, Centocor, GSK, Merck, Novartis, Pfizer, Roche, Schering-Plough, UCB, Wyeth, and is the owner of Rheumatology Consultancy bv, S. Liu Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., N. Mozaffarian Shareholder of: AbbVie Inc., Employee of: AbbVie Inc.