Aggressive Combination Therapy Reduces Risk of Heart Attack by 80% in People with Rheumatoid Arthritis

Newswise — The use of combination TNF-inhibitor-methotrexate therapy in people with rheumatoid arthritis was associated with a risk of heart attack that was reduced by 80 percent in comparison with those using methotrexate alone, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Boston, Mass.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of many joints. An estimated 2.1 million Americans have RA, most of them women. Although joints are the principal body parts affected by RA, inflammation can develop in other organs as well. Heart attacks, resulting from inflammation of the coronary vessels, are more common in RA sufferers.

Researchers recently studied the risk of heart attack in patients using a TNF-inhibitor (a drug that blocks cytokines and can reduce pain, morning stiffness and swollen joints in RA), methotrexate (a drug used to treat RA by blocking the metabolism of cells) and other DMARDs (a category of drugs used in many autoimmune disorders to slow down the disease progression) in a large population of patients with RA—many of whom were also taking aspirin.

Using data obtained from MediCal, California's Medicaid program, researchers studied patients over the age of 18, suffering from RA, who were treated with TNF-inhibitors, methotrexate, or other DMARDs, over six-and-a-half years.

A total of 19,233 patients with RA were identified. The patients' mean age was 55 years, and approximately 79 percent were women. Of these patients, 13,383 took methotrexate; 14,958 took other DMARDS; and 4,943 took TNF-inhibitors. Exposure to TNF-inhibitors (taken alone or in combination with methotrexate) was compared to taking methotrexate alone.

During the study period, 441 patients suffered heart attacks, of which eight percent were fatal.

Researchers found that patients on a combination of TNF-inhibitors with methotrexate treatment had a heart attack risk of only 20 percent of the risk compared to patients taking methotrexate alone.

However, there was no statistical difference seen among patients who were taking TNF-inhibitors alone, TNF-inhibitors with other DMARDs, other DMARD therapies without methotrexate, or a combination of DMARDs and methotrexate. "TNF-inhibitor therapy, in combination with methotrexate, dramatically reduces the risk of heart attacks in patients with RA and should be seriously considered— especially in high-risk patients," said Gurkirpal Singh, MD; adjunct clinical professor of medicine, division of gastroenterology and hepatology, Stanford University School of Medicine; chief science officer, Institute of Clinical Outcomes Research and Education; and an investigator in the study.The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR's annual meeting, see http://www.rheumatology.org/annual.

Editor's Notes: Dr. Singh will present this research during the ACR Annual Scientific Meeting at the Boston Convention and Exhibition Center from 4:30 " 6:00 pm ET on Friday, November 9, 2007, in Grand Ballroom East. Dr. Singh will be available for media questions and briefing at 8:30 am ET on Thursday, November 8 in the on-site press conference room, Room 251. Presentation Number: 1399

Combination TNF-Inhibitor-Methotrexate Therapy is Superior to Methotrexate Monotherapy in Reducing the Risk of Acute Myocardial Infarction in Patients with Rheumatoid Arthritis

Gurkirpal Singh1, Shweta Vadhavkar2, Alka Mithal2, George Triadafilopoulos1. 1Stanford University School of Medicine, Palo Alto, CA; 2Institute of Clinical Outcomes Research and Education (ICORE), Palo Alto, CA

Background: Patients with rheumatoid arthritis (RA) have an increased risk of fatal and non-fatal acute myocardial infarction (AMI), perhaps secondary to increased systemic inflammation. TNF inhibitors may reduce the risk of AMI because of their strong anti-inflammatory effect.

Objectives: We studied the risk of acute myocardial infarction with TNF-inhibitor therapy, methotrexate (MTX) and other DMARDs in a large population of patients with rheumatoid arthritis, many of whom were on concomitant aspirin therapy.

Methods: MediCal, the Medicaid program for California, is the largest Medicaid program in the US, with over 7 million participants per year. We used data from the MediCal program for a nested case control study of all patients over age 18 with physician-diagnosed rheumatoid arthritis treated with DMARDs, TNF-inhibitors or MTX between Jan 1, 1999 and June 30, 2005. Cases of acute myocardial infarction (AMI) were risk-set matched with 4 controls on age, gender and date of AMI. Current exposure to therapies was defined as filling a prescription within 60 days prior to index date. Current exposure to TNF-inhibitors (monotherapy, or in combination with MTX or other DMARDs) was compared to MTX monotherapy. All analyses were adjusted for 38 confounding risk factors (including surrogate variables for smoking and dyslipidemias) as well as concomitant aspirin and NSAID treatment (prescription or over-the-counter use).

Results: A total of 19,233 RA patients (mean age 54.7 years, 79.4% women) were identified. Of these, 13,383 patients took MTX, 14,958 other DMARDS and 4,943 TNF inhibitors. During 74,006 person-years of follow-up, 441 cases of AMI were identified, of which 8% were fatal. Combination TNF-inhibitor - methotrexate treatment significantly reduced the risk of AMI compared to MTX monotherapy (multivariate-adjusted relative risk 0.20 (95% CI 0.05 - 0.88, p<0.03). No statistical difference was seen with TNF-inhibitor monotherapy (RR 1.17, 95% CI 0.50 - 2.75), TNF-inhibitor with other DMARDs (RR 1.78, 95% CI 0.60 - 5.27), other DMARD therapies without MTX (RR 0.88, 95% CI 0.60-1.31) or a combination of DMARDs and MTX (RR 0.93, 95% CI 0.54-1.62) when compared with methotrexate monotherapy. Systemic corticosteroid use significantly increased the risk of AMI (adjusted RR 1.37, 95% CI 1.07 - 1.75, p<0.01). Conclusion: Combined TNF-inhibitor-Methotrexate therapy is associated with a reduction in the risk of acute myocardial infarction by 80% compared to methotrexate monotherapy in patients with RA. Such dramatic effect enhances the therapeutic gains of TNF-inhibitor therapy in patients with RA and should be seriously considered, particularly in high-risk patients.

Disclosure Block: G. Singh, Centocor, Pfizer, Novartis, 2; Pfizer, 8; S. Vadhavkar, None; A. Mithal, None; G. Triadafilopoulos, None.