A new Italian study has found that obese patients with longstanding rheumatoid arthritis (RA) who are put on anti-tumor necrosis factor (anti-TNF) therapies are less likely to achieve remission than their thinner counterparts.

The research, published online in Arthritis Care & Research recently, also found that, when it comes to obese patients, not all anti-TNFs are equal. Obese people who were taking infliximab (Remicade) were less likely to achieve remission than obese patients taking etanercept (Enbrel) or adalimumab (Humira).

There are five anti-TNFs – biologic medications that target the immune system – currently approved for RA: infliximab, etanercept, adalimumab, certolizumab pegol (Cimzia) and golimumbab (Simponi). The study did not include certolizumab pegol or golimumab, which are much newer than the others.

A growing body of research has shown that body fat (adipose tissue) produces inflammation that may make diseases such as RA worse. But researchers don’t yet completely understand why that happens or how treatment should be changed for people who are obese.

“Adipose tissue is a source of pro-inflammatory cytokines [proteins], and thus it may contribute to the inflammatory burden of the RA patient, creating a more inflammatory and therapy-resistant state,” explains lead author Elisa Gremese, MD, a researcher at the Catholic University of the Sacred Heart in Rome, Italy. “It has also been shown that obese RA patients have a more severe disease than normal weight patients, and this may also lead to a poorer therapy effect.”

The study involved 641 RA patients in Italy with established RA. All had tried taking methotrexate without benefit and so were stepped up to an anti-TNF. The participants were treated either with infliximab, adalimumab or etanercept and assessed at the start of the study as well as month three, six and 12. Remission was defined as having a DAS28 of less than 2.6 lasting for at least three months. DAS28 – Disease Activity Score in 28 joints – is a measure of disease burden and tender/swollen joints.

The researchers found that at the 12-month assessment, 30 percent of all patients had reached remission. But the rates were significantly different for patients who were obese (BMI more than 30) or non-obese (BMI less than 30): 15 percent of obese and 32 percent of non-obese patients achieved remission.

According to the study, remission rates broken down by anti-TNFs were:

• Infliximab (Remicade): 22 percent of non-obese and 0 percent of obese patients reached remission
• Adalimumab (Humira): 30 percent of non-obese and 15 percent of obese patients reached remission
• Etanercept (Enbrel): 36 percent of non-obese and 28 percent of obese patients reached remission

Dr. Gremese says she is not certain why infliximab seems to be less effective in obese people. Infliximab is the only one of the three anti-TNFs in the study that is dosed by weight, although Dr. Gremese says she doesn’t think that factor is responsible for the difference in patient benefit.

She speculates that fat tissue may be at the root of the problem, and says more research is needed to understand its role.

While the study looked only at a select group of therapies, Dr. Gremese says the researchers want to learn if the findings apply to the other anti-TNF drugs (certolizumab pegol and golimumab) as well as the biologics that work via a different mechanism (rituximab (Rituxan), anakinra (Kineret), tocilizumab (Actemra) and abatacept (Orencia)). Dr. Gremese explains that each drug must be individually analyzed because small differences in their make-up could cause unique responses. 

Dr. Gremese says research also is needed to verify whether anti-TNFs are “the best first choice” in obese RA patients. “We want to learn whether other drugs, with different mechanisms of action, could offer the best chance of [providing remission].”

Olivia Ghaw, MD, assistant professor of medicine and rheumatology at Icahn School of Medicine at Mount Sinai, in New York City, says the study could influence practice. “If the results of the study can be confirmed, rheumatologists may start reaching for etanercept and adalimumab rather than the other medications,” she says.

Dr. Ghaw agrees with the conclusion of the study authors: Treatment needs to be highly personalized to the individual patient. But she thinks the treatment plan needs to include more than just medications. “In addition to the drug therapy, there are lifestyle modifications patients can initiate themselves – stop smoking, lose weight, exercise – that can create changes in disease activity,” she says.

Dr. Gremese says “personalized therapy” would mean physicians “determine the best therapeutic choice on the basis of the characteristics of the individual patient, and so, in this case, [it] would mean choosing the drug that provides the best proven opportunity of response in the obese RA patient.”