RA Combo Treatments After First Rx Fails

DMARD combination therapy and Enbrel plus methotrexate led to similar rheumatoid arthritis improvement

/ Author:  / Reviewed by: Robert Carlson, M.D

(RxWiki News) Methotrexate is often the first choice of medication to treat rheumatoid arthritis (RA). When methotrexate alone doesn't do the trick, patients may take a combination of other medications. So, what's a good combination?

In a recent study, researchers set out to compare two combination treatments for rheumatoid arthritis. 

The first combination was a more traditional treatment consisting of three disease-modifying antirheumatic drugs (DMARDs), including methotrexate. The second combination included methotrexate and etancercept (brand name Enbrel), which is part of a newer class of medications.

The researchers found that patients in both treatment groups had similar improvement in their number of tender or swollen joints, a key measure of rheumatoid arthritis.

There was also no large difference between the groups in terms of harmful side effects related to the medications.

"Work with a rheumatologist to find the best treatment for you."

This double-blind, non-inferiority trial was conducted by James R. O'Dell, MD, from the VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center in Omaha, and a team of fellow researchers.

A non-inferiority trial is meant to show that the effect of one treatment is no worse, or not inferior, than another. Double-blind means that neither the participants nor the researchers knew which medications the participants were taking.

According to Dr. O'Dell and colleagues, there have been few blinded studies that have compared a combination of DMARDs to biologic medications in the treatment of patients with RA who have not responded to methotrexate.

Methotrexate is a DMARD that is typically the first line of treatment for patients with RA. Rather than only relieving symptoms, methotrexate and other DMARDs actually control the disease activity of RA. 

When methotrexate on its own does not reduce disease activity, doctors may prescribe other DMARDs. Research has shown that patients who are treated early with DMARDs have a good chance of controlling their RA.

In recent years, though, a newer class of medications has emerged. These medications — called biologics — are used when patients do not respond to the traditional DMARDs.

From their study, Dr. O'Dell and team wanted to see if a combination of three DMARDs — which included methotrexate plus sulfasalazine (brand name Azulfidine) and hydroxychloroquine (brand name Plaquenil) — was just as effective as etanercept plus methotrexate.

The 48-week study included 353 rheumatoid arthritis patients who had been treated with methotrexate but still had active disease. These patients were assigned to take either the triple DMARD therapy or etanercept plus methotrexate.

Patients whose RA did not improve by 24 weeks were switched to the other treatment.

To measure disease activity, the researchers used the DAS28, which stands for "disease activity score in 28 joints." The DAS28 takes into account the number of tender or swollen joints out of a total of 28 joints. For this study, DAS28 scores ranged from 2 to 10, with higher scores being a sign of more disease activity.

The researchers found that patients in both treatment groups had improved disease activity in the first 24 weeks of the study.

From the beginning of the study to 48 weeks later, both groups had similar improvement in DAS28 scores. The DAS28 score improved by 2.1 points in triple DMARD group and by 2.3 in the etancercept plus methotrexate group.

The researchers also found no significant differences between groups in radiographic progression (disease progress as shown through x-ray), pain, health-related quality of life and harmful side effects associated with the medications.

"With respect to clinical benefit, triple therapy, with sulfasalzine and hydroxychloroquine added to methotrexate, was non-inferior to etanercept plus methotrexate in patients with rheumatoid arthritis who had active disease despite methotrexate therapy," the researchers concluded.

In other words, treatment with these three DMARDs appeared to be just as effective as etanercept plus methotrexate in treating RA patients who did not respond to methotrexate alone.

Mark Newberry, PharmD, pharmacist and owner of Tarrytown Pharmacy, said "Treating RA with the triple therapy of methotrexate, sulfasalazine, and hydroxycholorquinone, should be considered as effective as the dual therapy of etanercept and methotrexate.  If you also take in to account the cost of medication therapy, which should always be a deciding factor, then the triple therapy would save the patient over $10,000 per year."

This study was published on June 11 in the New England Journal of Medicine.

The research was funded by the Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, and others.

Some of the study's authors reported financial ties to various pharmaceutical companies as well as the Canadian Institutes of Health Research (CIHR), the US Department of Veterans Affairs and the Veterans Administration.

Reviewed by: 
Review Date: 
June 9, 2013
Last Updated:
August 7, 2013