Methotrexate and Anti-TNFs Associated with Decreased Risk of Cardiovascular Complications in People with Rheumatoid Arthritis

Newswise — CHICAGO – Taking methotrexate or anti-TNFs is associated with a reduction in risk of cardiovascular disease in people with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago.

Methotrexate and anti-TNFs are among the most effective and commonly used treatments of inflammatory rheumatic diseases, such as rheumatoid arthritis. Previous studies have shown that these medications are associated with reducing the risk of coronary artery disease (called CAD; a disease that causes a narrowing of the blood vessels that supply the heart with oxygen) in people with RA, and researchers have recently looked at each medication individually to confirm this association.

Led by Rasa Bozaite-Gluosniene, MD, the research team identified 1,829 people from the U.S. with newly diagnosed RA (who did not have pre-existing CAD) between 2001 and 2009. Of this group, 1,119 were (at some point) taking methotrexate (Rheumatrex®, Trexall® ) and 710 were not; 588 were (at some point) taking anti-TNFs (Enbrel®, Humira®, and Remicade®) and 1,241 were not.

The researchers followed electronically each patient’s exposure to the two medications to see if any developed CAD (which would have been identified by a billing code for disease diagnosis or a cardiac revascularization procedure). During this time, the researchers took into consideration other characteristics associated with risk of CAD, such as age, gender, blood pressure (including high blood pressure), cholesterol (both ‘good’ and ‘bad’), diabetes, rheumatoid factor, body mass index, and use of other types of medications (such as statins, hydroxychloroquine, steroids or nonsteroidal anti-inflammatory drugs).

Dr. Bozaite-Gluosniene’s team noted that those who took methotrexate or anti-TNFs developed fewer new cases of CAD than those who did not. In those taking methotrexate versus whose who weren’t, the rate of new cases of CAD was 37.5 vs. 17.6 per 1,000 person-years of observation, respectively. Patients on methotrexate had 46 percent lower likelihood of CAD events than those not on methotrexate.

For methotrexate use that lasted more than 24 months, the risk of developing CAD was reduced by 67 percent as compared to those not taking methotrexate. In those taking anti-TNFs versus those who were not, the rate of new cases of CAD was 11.8 versus 32.1 per 1,000 person years. Overall, among those taking anti-TNFs there were 46 percent less likely to have a CAD event than patients not on anti TNFs. In participants taking anti-TNFs more than for more than 24 months, the likelihood of developing CAD was reduced by 76% as compared to those not taking it.

“RA is a systemic inflammatory condition with cardiovascular disease being the major cause of death,” says Androniki Bili, MD, MPH; associate, Department of Rheumatology, Geisinger Medical Center, Danville, Pa. and an investigator in the study. “Medications that effectively control RA inflammation may be associated with reduction in cardiovascular risk.”

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.

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit www.rheumatology.org/education. Follow the meeting on Twitter by using the official hashtag: #ACR2011.

Editor’s Notes: Androniki Bili, MD, MPH, will present this research (including updated data) during the ACR Annual Scientific Meeting at McCormick Place Convention Center at 11:30 AM on Sunday, November 6 in Room W375d.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover the ACR’s Simple Tasks campaign, which highlights the severity of rheumatic diseases and the importance of early and appropriate referral to a rheumatologist

Presentation Number: 719

Reduced Cardiovascular Risk with Use of Methotrexate and Tumor Necrosis Factor-α Inhibitors in Patients with Rheumatoid Arthritis

Rasa Bozaite-Gluosniene (Geisinger Medical Center, Danville, PA)Xiaoqin Tang (Geisinger Center for Health Research, Danville, PA)H. Lester Kirchner (Geisinger Center for Health Research, Danville, PA)Jana L. Antohe (Geisinger Health System, Danville, PA)Stephanie J. Morris (Rose Tree Medical Associates---Riddle Memorial Hos, Danville, PA)Mary Chester Wasko (Temple University School of Medicine, Pittsburgh, PA)Androniki Bili (Geisinger Medical Center, Danville, PA)

Presentation Number: 719

Background/Purpose: Methotrexate (MTX) and tumor necrosis factor (TNF)-α inhibitors have been associated with a reduction of incident coronary artery disease (CAD) in rheumatoid arthritis (RA) patients. Here we examine the independent contribution of each medication on risk of CAD.

Methods: Using an inception cohort of 1829 RA patients without preexisting CAD, diagnosed between 1/1/2001 3/31/2008 were identified. Patients were classified as users (n=1119) or nonusers (n=710) of MTX and users (n=588) or nonusers (n=1241) of TNF-α inhibitors (etanercept, adalimumab, infliximab). Medication exposure was analyzed in time-varying fashion using medication start and stop dates, allowing patient drug exposure status to change over time. Outcome was incident CAD (ICD-9 410. - 419.99 or cardiac revascularization procedure). Cox proportional hazard regression models were used to estimate the associations on developing incident CAD after adjusting for age, gender, hypertension, hyperlipidemia, diabetes, rheumatoid factor, BMI, blood pressure, LDL, ESR, hydroxychloroquine, MTX, corticosteroid and NSAID use. Exposure to MTX, TNF-α inhibitors and all other variables were treated as time-variant in models.

Results: In MTX nonusers and users groups, incidence rate (IR) for CAD was 37.5 vs.17.6 events per 1000 person-years (p-y), respectively. Among MTX users, the hazard for incident CAD was 0.54 (95% confidence interval (CI) 0.37, 0.77; p=0.001) compared to nonusers; among those taking MTX for more than 24 months the hazard was 0.33 (95% CI 0.22, 0.50; p<0.001). In TNF- α inhibitors nonusers and users groups, IR for CAD was 32.1 vs.11.8 events per 1000 p-y, respectively. Among TNF- α inhibitor users the hazard for incident CAD was 0.54 (CI 0.30, 0.95; p=0.03) compared to nonusers; among those taking TNF- α inhibitor for more than 24 months hazard was 0.24 (95% CI 0.12, 0.51; p<0.001).

Conclusion: In this inception RA cohort, the use of MTX or TNF-α inhibitors was independently associated with a 46% reduction in incident CAD compared to nonusers; for MTX or TNF-α inhibitor use for more than 24 months the risk was further decreased by 67% and 76% respectively, raising the possibility that TNF-α inhibitor use offers additional cardioprotective effect in RA patients.

Disclosure: R. Bozaite-Gluosniene, None; X. Tang, None; H. L. Kirchner, None; J. L. Antohe, None; S. J. Morris, None; M. C. Wasko, None; A. Bili, None.