June 20, 2012

Good News and Bad News for Anti-TNF Treatment of Rheumatoid Arthritis

Washington, D.C.Antitumor necrosis factor drugs appear to lower risk of cardiovascular events in rheumatoid arthritis patients, according to a large study that also suggests that the longer the drugs are used, the better. Another study, however, points to some of the downsides of the therapy.

The study, a retrospective analysis of contemporary data, indicates that the cumulative use of anti-TNFs for 1, 2, or 3 years is associated with reduced risk of cardiovascular events by 24%, 42%, and 56%, respectively, compared to patients who weren’t using those therapies, according to a presentation at EULAR 2012, the Annual Congress of the European League Against Rheumatism.

The model, based on more than 100,000 patients, demonstrated that each additional 6 months of treatment with anti-TNFs significantly reduces the risk of cardiovascular events, defined as myocardial infarction, stroke/transient ischemic attack, unstable angina, or heart failure.

Results also were promising in older rheumatoid arthritis patients, those more than 50 years old, and those without prior treatment with methotrexate.

"RA and heart disease have a common origin and the systemic inflammation involved in RA is thought to also promote cardiovascular disease and even cardiovascular death. Studies have shown that within the first 10 years of being diagnosed with RA, the risk of a heart attack almost doubles," said lead study author Dr. Michael Nurmohamed, VU University Medical Centre & Jan van Breemen Research Institute, Reade, The Netherlands. "As anti-TNFs are now the treatment of choice for patients who are unstable on methotrexate, the decreased cardiovascular risk observed in the study is an added bonus to an already successful class of drugs."

The study used U.S. health plan claims to identified 109,462 patients who had a rheumatoid arthritis diagnosis and had filled prescriptions for anti-TNF therapy, methotrexate therapy, and/or other nonbiologic DMARD. A total of 1,743 patients (1.6%) had a cardiovascular event after their index prescription, researchers noted.

While the cardiovascular benefits of anti-TNF were found to be promising, a downside of using the drugs also was identified in a presentation at the same conference. Patients with inflammatory rheumatic diseases treated with anti-TNFs have a 75% greater risk of developing herpes zoster than patients treated with traditional disease modifying antirheumatic drugs, according to a meta-analysis of previously published studies.

"Anti-TNFs, such as infliximab, adalimumab, and etanercept have become the treatment of choice for patients with inflammatory rheumatic diseases who are uncontrolled on traditional [therapies], but it is known that a side effect of these drugs is an increased risk of bacterial infections," said lead author Helene Che of Lapeyronie Hospital in France. "This systematic review and meta-analysis demonstrates that careful monitoring of patients treated with anti-TNFs is required for early signs and symptoms of herpes zoster and raises the issue as to when vaccination against the virus should occur."

For the study, a literature search was conducted in Medline, Embase, the Cochrane library and abstracts from American College of Rheumatology and EULAR congresses from 2006 to 2010.

Studies were included in the meta-analysis if they reported incidences of herpes infection in either anti-TNF and conventionally treated patients. From the 657 articles, 134 congress abstracts, and 11 national registries included in the literature search, 22 articles and 28 abstracts met eligibility criteria and were included in the study.

“These data raise the issue of a systematic prophylactic treatment in patients with a known history of herpetic infections, or vaccination in na├»ve patients,” according to the authors.

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