Biologic agents do more than slow the progression of autoimmune forms of arthritis; they also can help you live longer, according to a new study presented recently in Berlin, at the annual congress of the European League Against Rheumatism, or EULAR.

It is already known that treating rheumatoid arthritis, or RA, can help you live longer, and that untreated RA can lower life expectancy. But this study shows a mortality benefit even over traditional disease modifying anti-rheumatic drugs, or DMARDs, such as methotrexate, hydroxychloroquine and leflunomide.  

Yet experts, including the study author, stress it is not necessarily the biologic increasing life expectancy, but better control of the disease.

“Patients with highly active rheumatoid arthritis have a shorter life expectancy than subjects from the general population with equal age and gender,” says lead study author Joachim Listing, PhD, head of the group statistics and clinical trials at the German Rheumatism Research Center in Berlin. “That means they die on average five years earlier. Patients in whom the disease is successfully controlled by disease modifying anti-rheumatic drugs – [traditional] or biologic – have, compared to those with active disease, an increased life expectancy.”

The German study looked at nearly 9,000 patients with rheumatoid arthritis. It found the mortality rate in those using biologic agents to be roughly half that of those using traditional DMARDs.

Researchers measured mortality in patient/years. Patient/years is a way of following trends in a group of people. In this case, for every 1,000 patients on an anti-TNF biologic – such as etanercept, or Enbrel; infliximab, or Remicade; and adalimumab, or Humira – there were 10.6 deaths over a one-year period. For those using the biologic rituximab – or Rituxan, a selective B-cell inhibitor – there were 12.7 deaths, and for those using a traditional DMARD, there were 20.6 deaths.

Biologic agents differ from traditional DMARDs in that they are genetically engineered to target a specific part of the immune system responsible for the inflammation seen with RA and other types of inflammatory arthritis. In addition to anti-TNFs and selective B-cell inhibitors, other biologics target interleukin-1 (anakinra, or Kineret), interleukin-6 (tocilizumab or Actemra), or work as a selective co-stimulation modulator (abatacept, or Orencia).
 

The study also analyzed life expectancy data among the participants, and found those with RA have an overall reduction of 2.2 years when compared with the general population. Yet study participants who scored well (below 4.1) on the DAS28 measure – which looks at disease activity in the 28 joints RA commonly affects – had normal life expectancies. On the other hand, DAS28 scores higher than 4.1 cut life expectancy by 5.6 years in women and 4.8 years in men.

David Pisetsky, MD, PhD, chief of the division of rheumatology and immunology at Duke University Hospital in Durham, NC, calls the study important. “What this really enforces is, if the disease is brought under better control, there’s a survival benefit.

“If the disease is not under control, certainly biologics become an option. But they are not the only option,” Dr. Pisetsky adds. “If the disease is under control with methotrexate [a traditional DMARD], I don’t see a need to switch to a biologic.”

“For a patient in remission, these data are not clear that a biologic will be helpful,” says Mark C. Fisher, MD, MPH, a rheumatology specialist at Massachusetts General Hospital in Boston. “For a patient who still has moderate or severe disease activity, this study provides evidence to justify rapid escalation that includes a biologic agent.”

Dr. Fisher is not surprised by the study findings. “Systemic inflammation contributes to cardiovascular risk in RA, and that is likely one avenue through which [biologics] are helpful.”

Dr. Fisher says the drugs, while useful, are contraindicated in some patients. “Patients with a history of recurrent infections, patients with active malignancies, or, for the TNF inhibitors, the presence of a demyelinating syndrome or heart failure would all be reasons to avoid using a biologic agent,” he says.

Eric Matteson, MD, chairman of Mayo Clinic’s rheumatology division in Rochester, Minn., says biologics are just part of an improving picture for patients with RA. “Overall, the life expectancy and quality of life of patients with rheumatoid arthritis has improved greatly in the past 20 years, even before biologics came into use. This trend is continuing, and perhaps even accelerating,” he says.

“This study does not imply that biologics are needed for everyone, nor do we really know for sure if there are other aspects about the patients who get, and those who do not get, biologics – like their socio-economic status, education, etc., that may be playing a role here,” notes Dr. Matteson. “The most important thing is to use the medications that are appropriate for controlling the disease as early as possible, but also throughout the course of the disease.”