BIRMINGHAM, ENGLAND – The risk of heart attack appears to be lower in patients treated with anti–tumor necrosis factor therapy than with conventional disease-modifying antirheumatic drugs.
Patients treated with the biologic agents had a 30% lower risk for having a myocardial infarction, based on data from the British Society for Rheumatology Biologics Register (BSRBR) for rheumatoid arthritis. However, no differences were detected in 30-day or 1-year mortality rates (adjusted hazard ratios of 0.9 and 0.97, respectively).
"There seems to be a signal that subjects ever exposed to anti-TNF therapy were potentially at reduced risk for developing an MI," Dr. Audrey Low said in an interview at the British Society for Rheumatology annual conference.
Dr. Low, a clinical research fellow in the Arthritis Research UK Epidemiology Unit, University of Manchester, England, explained that traditional risk factors do not fully account for the well-known increased risk for cardiovascular disease in patients with rheumatoid arthritis. Underlying inflammation might play a role, and it was hypothesized that anti-TNF therapy might help to reduce this inflammation, with subsequent cardiovascular benefits.
The BSRBR-RA is one of the largest biologics registers in the world and has been running for more than 10 years. The register currently includes data on more than 20,000 participants treated with either anti-TNF agents or nonbiologic disease-modifying antirheumatic drugs (DMARDs), such as methotrexate.
The present study used data collated between 2001 and 2008 on 11,536 patients treated with anti-TNF drugs licensed at the time in the United Kingdom (etanercept, infliximab, and adalimumab), and 3,225 patients who received nonbiologic DMARDs. Patients with prior MI or angina were excluded, and patients were followed up through April 2010 or until death, incident MI, or date of last clinician assessment, whichever came first.
Patients treated with anti-TNF therapy were younger than those given nonbiologic DMARDs, with a mean age of 56 years versus 60 years at recruitment into the BSRBR-RA. They also tended to have higher disease activity and longer disease duration (11 years vs. 6 years). There were similar percentages of patients with hypertension (29% vs. 32%), diabetes (6% for both), and a history of ever having smoked (59% vs. 62%).
There were 224 incident MIs in the anti-TNF–treated group at a median follow-up of 6 years per person, and 52 heart attacks in the nonbiologic DMARD–treated group at a median follow-up of 4 years per person. "Even though the study has been running for over 10 years, the amount of follow-up per person is between 4 and 6 years," Dr. Low observed.
The unadjusted hazard ratio for MI risk was 0.9, and it increased to 1.2 when adjusted for age and gender. "The hazard ratio goes up as you’d expect," Dr. Low observed. "People in the anti-TNF cohort are younger, and there are more females [77% vs. 74% for nonbiologic DMARDs]."
After adjustment for risk factors, analysis gave a hazard ratio of 0.7 in favor of anti-TNFs reducing the risk for MI. The risk factors included disease-specific factors (age, gender, disease duration, disease activity, steroid exposure, number of previous nonbiologic DMARDs received, and year of entry into the study), as well as traditional cardiovascular risk factors (hypertension, diabetes, smoking, chronic obstructive pulmonary disease, antiplatelet therapy, and use of nonsteroidal anti-inflammatory drugs and COX-2 inhibitors). "Statins were also included in the adjustment," Dr. Low confirmed.
The possible reduction in the risk for heart attack is another potential benefit of anti-TNFs that can be discussed with patients, she suggested, although patients would of course not be put on these drugs in order to reduce their cardiovascular risk.
Why anti-TNFs have this effect is still not clear. Dr. Low said. "It’s going to be very difficult to tease out whether it’s the inflammation that has been reduced by the anti-TNF therapy or whether anti-TNF therapy affects other factors, such as hypertension and lipids, but I don’t think we can say that for certain from this analysis.
Further research will look at the effect of anti-TNFs on the severity of MI to see if there is any difference from nonbiologic DMARDs.
The BSRBR is funded by a grant from the British Society for Rheumatology (BSR), which receives funding from multiple drug companies. This income finances a wholly separate contract between the BSR and the University of Manchester to host the BSRBR. Dr. Low had no conflicts of interest.