Anti-TNFs Found to Reduce Risk of Acute Coronary Syndrome in Rheumatoid Arthritis Patients

Article ID: 609030

Released: 18-Oct-2013 2:00 PM EDT

Source Newsroom: American College of Rheumatology (ACR)

Newswise — SAN DIEGO — Tumor necrosis factor inhibitor drugs (commonly called Anti-TNFs) modestly reduce the risk of acute coronary syndrome, such as heart attacks and angina, in rheumatoid arthritis patients whose inflammation places them at higher risk of developing coronary heart disease, according to new research findings presented this week at the American College of Rheumatology Annual Meeting in San Diego.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men. High risk of coronary heart disease in RA patients has been linked to inflammation and disease severity, making effective management of these factors highly important.

Anti-tumor necrosis factor drugs are a class of drugs that have been used for more than 10 years. They are used worldwide to treat inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, juvenile arthritis, Crohn's colitis, ankylosing spondylitis and psoriasis. These drugs are able to reduce inflammation and stop disease progression.

Researchers in Sweden sought to determine if use of tumor necrosis factor inhibitor drugs to treat RA would result in a reduced risk of acute coronary syndrome (commonly called ACS), defined as a diagnosis of a heart attack or unstable angina (the worsening or increasing cardiac symptoms)

“As modern therapeutic alternatives in RA often make it possible to achieve a good control of joint inflammation, it is important to evaluate if this can also affect comorbidities,” says Lotta Ljung, MD, senior consultant, rheumatology; Umea University Hospital; and lead investigator in the study. “Patients with RA have a doubled or so risk for acute coronary syndrome, and cardiovascular prevention is thus a major task for rheumatologists.”

The researchers looked at the rates of coronary heart disease among RA patients using TNF inhibitors as compared to RA patients not using the drugs and the general population. The researchers identified a cohort of 7,704 RA patients from the Swedish Biologics Register with no previous incidence of ischemic heart disease who started their first TNF inhibitor between 2001 and 2010. The patients in this group were 75.9 percent female with an average age of 57.1 years. A comparator cohort of 23,112 matched, patients with RA who had never taken a biologic were identified from the National Patient Register. As a second comparator group, 38,520 matched individuals were randomly selected from the general population register.

Patient data was analyzed according to three periods of exposure to TNF inhibitors. “Actively” on TNF inhibitors was defined as taking the drugs until date of termination plus 90 days. “Short-term exposure” was defined as taking TNF inhibitors to two years. “Ever” was defined as having ever taken the medication. Acute coronary syndrome was defined as any primary discharge diagnosis of heart attack, unstable angina, or heart attack as cause of death from the Patient Register and the Cause-of-Death Register, respectively.

ACS occurred in the general population at a rate of 3.3/1,000 person-years, compared to 5.7 /1,000 person-years among those patients with RA actively on TNF inhibitor treatment and 8.6/1,000 person-years among those with RA who had never taken a biologic medication. Compared with the general population, and after controlling for confounding factors (such as disease duration, other co-existing diseases and socio-economic factors), patients with RA actively on TNF inhibitor treatment were 50 percent more likely to have ACS, while those who had never taken these medications were over twice as likely to have ACS. Compared to those who have never taken anti-TNF medication, the risk of ACS for patients actively on treatment was 27 percent lower. Similar risk estimates were observed in the other definitions of follow-up.

“This nationwide study adds to the evidence that use of TNF inhibitors for RA also has an impact on cardiovascular comorbidity,” Dr. Ljung says. “Whether the lowered risk of ACS is attributable to the TNF inhibitors as such, or is an effect of better inflammatory control, cannot be determined from this study. The increase in risk of ACS in patients with RA was lower, but not abolished by the treatment. Therefore, individualized cardiovascular prevention is needed for most patients.”

The American College of Rheumatology is an international professional medical society that represents more 9,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Meeting is the premier meeting in rheumatology. For more information about the meeting, visit or join the conversation on Twitter by using the official hashtag: #ACR13

Editor’s Notes: Dr. Ljung will present this research during the ACR Annual Meeting at the San Diego Convention Center at 3:00 PM on Sunday, October 27 in Room 30 E. Dr. Ljung will be available for media questions and briefing at 8:30 AM on Monday, October 28 in the on-site press conference room, 27 AB.

Abstract Number: 804

Tumour Necrosis Factor Inhibitors and The Risk Of Acute Coronary Syndrome In Rheumatoid Arthritis – a National Cohort Study

Lotta Ljung1, Johan Askling2, Solbritt M. Rantapää-Dahlqvist1, Lennart T.H. Jacobsson3 and The ARTIS Study Group2, 1Umeå University, Umeå, Sweden, 2Karolinska Institutet, Stockholm, Sweden, 3Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

Background/Purpose:The high risk of ischemic heart disease (IHD) in patients with rheumatoid arthritis (RA) has been linked to inflammation and disease severity. Treatment with tumour necrosis factor inhibitors (TNFi) can modify cardiovascular risk factors and are often effective in reducing disease activity. The objective of the study was to evaluate the risk of acute coronary syndromes (ACS) in patients treated with TNFi for RA compared with the risk in bio-naïve RA patients and in the general population.

Methods: In the Swedish Biologics Register we identified a cohort of patients, with RA and no previous IHD, starting their first TNFi 2001-2010 (n=7,704, mean age 57.1 years, 75.9% women). Matched bio-naïve referents were randomly selected (3:1, n=23,112) from the underlying national cohort of all individuals with two or more outpatient diagnoses of RA (one of which at a dept. for Rheumatology or internal medicine) as identified in the National Patient Register. Furthermore, a matched comparator cohort (5:1, n=38,520) was randomly selected from the Population Register. Covariates were obtained from the Patient register (joint surgery, disease duration, and prevalent diagnoses of hypertension, diabetes, chronic pulmonary disease, infection, cerebrovascular disease and other atherosclerotic disease,) and Statistics Sweden (educational level and previous work disability). Three exposure windows were defined; Actively on TNFi – Until date of termination of TNFi therapy +90 days, Short term exposure – limiting the follow-up on TNFi to 2 years, and Ever exposed to TNFi. The outcome, incident ACS, was defined as a primary discharge diagnosis of myocardial infarction, or unstable angina, or myocardial infarction as the underlying cause of death. Incidence rates were calculated and Cox Proportional Regression models were utilized for risk estimations.

Results: The fully adjusted hazard ratios, HR (95%CI), for TNFi exposed compared with bio-naïve RA patients were for Short term exposure 0.78 (0.61-1.01), Actively on TNFi 0.73 (0.60-0.89), and Ever exposed 0.82 (0.70-0.95). Comparing the bio-naïve RA cohort with the general population fully adjusted models resulted in the HRs Short term exposure 2.27 (1.88-2.73), Actively on TNFi 2.10 (1.82-2.43), and Ever 13exposed 2.03 (1.80-2.29) for the risk of ACS. The corresponding HRs for the TNFi cohort compared with the general population referents were 1.65 (1.23-2.22), 1.50 (1.21-1.85), and 1.61 (1.36-1.92) respectively.

Conclusion: In this nation-wide, population-based, matched cohort study treatment with TNFi was associated with a modest reduction of the risk of ACS in patients with RA. Compared with the general population the risk of ACS in RA was increased, although less pronounced among the TNFi exposed patients. The decrease in risk could be attributable to the TNFi per se, or correspond to a higher degree of inflammatory control in the treatment group.

Disclosures: L. Ljung, Bristol Myers Squibb, 5 J. Askling, Pfizer Inc, 2 S. M. Rantapää-Dahlqvist, None L. T. H. Jacobsson, Pfizer , 2, Pfizer , 5, UCB, 5, Abbvie , 5 T. ARTIS Study Group, Merck, BMS, Pfizer, Abbott Laboratories, SOBI, UCB, and Roche, 9


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