Keeping RA in Check May Lower CV Risk Over Time

Diedtra Henderson

April 02, 2015

Patients whose rheumatoid arthritis (RA) is kept in check over time by immunomodulatory treatments may also have the added benefit of eda substantial reduction in risk for cardiovascular (CV) events, independent of immunomodulatorythe type of treatment used treatments, according to a prospective study.

Daniel H. Solomon, MD, from the Division of Rheumatology and Division of Pharmacoepidemiology, Brigham and Women's Hospital, Boston, Massachusetts, and coauthors published their findings online March 16 in Arthritis & Rheumatology.

According to the National Institutes of Health, some 1.5 million people, or 0.6% of US adults, suffer from RA, an autoimmune disease that disproportionately affects women. Dr Solomon and colleagues write that "treat to target," an approach that is growing in popularity and seeks to lower disease activity or nudge RA into remission, heightens the importance of knowing more about the interplay between disease activity and CV risk.

They examined the Consortium of Rheumatology Researchers of North America (CORRONA), a registry for which 268 rheumatologists in 35 states use structured forms to contribute such data as patients' disease activity, medications, and CV risk factors. The Clinical Disease Activity Index measure includes the physician's report of the number of tender and swollen joints the patient has and reflects both the clinician's and the patient's assessment of global arthritis activity. Clinical Disease Activity Index values range from 0 to 76.

The researchers followed 24,989 patients with RA for nearly 3 years after their baseline visit until the first of the following occurred: December 30, 2011, patients were lost to follow-up, suffered their first CV event, or died. Seventy-six percent were women, and most had RA for a decade. In terms of treatment, 61% used nonsteroidal anti-inflammatory drugs or selective COX-2 inhibitors, 84% used methotrexate, and 48% used a tumor necrosis factor antagonist.

"Among a large cohort of patients with RA followed for a median of 2.7 years, we found a significant trend towards a reduced risk of CV events with improved disease activity: a 21% reduction in CV risk for each 10 point lowering of the [Clinical Disease Activity Index,] and a 53% reduction from high disease activity to remission," Dr Solomon and coauthors write. "These results add significant new information regarding the importance of sustained control of RA disease activity, not only for improvement in pain and function, but also for reduced CV risk."

Earlier RA studies showed an association between methotrexate and tumor necrosis factor blockers and reduced CV risk, but it was unclear whether that was a result of the medicines or the lowered disease activity. The new study clarifies the issue, but the finding would be strengthened by randomized trials and a longer follow-up period, Michael T. Nurmohamed, MD, PhD, from the Amsterdam Rheumatology immunology Center, VU University Medical Center & Reade, Amsterdam, the Netherlands, writes in an accompanying editorial.

"Altogether, this study suggests that aiming at low disease activity or remission also has favourable effects on the CV risk of our patients that is independent of the type [of] antirheumatic drugs used," Dr Nurmohamed writes. "[C]ontrolling disease activity/inflammation, from a CV point of view, counts more than the drug used to achieve the low disease state or remission."

Among the strengths of the study Dr Solomon and colleagues point to are "typical real-world clinical practice" and information about such CV risk factors as body mass index, tobacco use, and family history.

"The results demonstrate a clear 'dose-response' effect with reductions in disease activity associated with reduced CV risk, independent of immunomodulatory treatments," the researchers conclude. "While these findings should not be interpreted to mean that traditional risk factors are not important, they do support the current RA recommendations for treating to low disease activity or remission."

Financial support for the study was provided by CORRONA, which has received subscription fees from Abbvie, Amgen, AstraZeneca, Genentech, Horizon, Eli Lilly, Novartis, Pfizer Inc, Vertex, and UCB. One coauthor disclosed receiving pass-through research grants given to his institution by Amgen, Eli Lilly, and Pfizer and serving in unpaid roles on a trial sponsored by Pfizer. Another coauthor disclosed receiving a salary from and owning stock in CORRONA and receiving consulting fees and research support from Abbvie, Amgen, BMS, Genentech, Eli Lilly, Pfizer, and UCB. Another coauthor disclosed receiving research grants from and consulting for Abbvie, Amgen, Genentech/Roche, and Pfizer and receiving support from the Agency for Healthcare Research and Quality and the National Institutes of Health. Another coauthor disclosed having been an advisor for Genentech. Another coauthor disclosed receiving research support from CORRONA that passes through his institution. Another coauthor disclosed being a consultant for Iroko Pharmaceuticals, Novartis AG, and Pfizer. Another coauthor disclosed being a paid consultant for AstraZeneca and Pfizer. The two remaining authors and Dr Nurmohamed have disclosed no relevant financial relationships.

Arthritis Rheum. Published online March 16, 2015. Article abstract


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