Triple therapy works just as well as methotrexate plus a biologic for patients with active rheumatoid arthritis (RA), according to a new study published online in The New England Journal of Medicine. The results of this study may help guide treatment for patients who don’t improve enough on methotrexate alone.

Methotrexate is a traditional disease-modifying antirheumatic drug (DMARD) that slows the progression of RA (and certain other types of inflammatory arthritis). If methotrexate alone is not enough to bring about improvement, it can be combined with sulfasalazine plus hydroxychloroquine (called “triple therapy”). It also can be combined with a biologic drug, such as adalimumab (Humira), etanercept (Enbrel) or infliximab (Remicade), to make treatment more effective. But which treatment regimen gets the best results for patients is not entirely clear because, as the study authors note, few head-to-head comparisons had been done.

“Both are effective therapies. We knew that and this confirms it,” says lead author James R. O’Dell, MD, chief of rheumatology at the University of Nebraska Medical Center in Omaha.

For his study, Dr. O’Dell and his colleagues followed 353 RA patients for 48 weeks. All of the study participants had active disease, even though they were taking methotrexate. They continued treatment with methotrexate and were randomly assigned to receive either sulfasalazine plus hydroxychloroquine, or etanercept. Neither doctor nor patient knew which drug regimen a patient was getting. Patients were assessed every six weeks. At 24 weeks, if a patient was not doing well, he or she was switched to the other treatment (still without knowing which treatment they were getting).

After 24 weeks, the majority of the patients were doing well and continued with their assigned regimen, but equal numbers – 27 percent – from each group were switched to the other treatment. Twenty-four weeks after they switched treatments, all patients were equally improved as measured by DAS28 scores (a measure of disease activity that assesses 28 joints as well as inflammatory markers in the blood) and radiographic progression (joint damage as seen on an X-ray).    

Dr. O’Dell says he was surprised by the results. “No one would have predicted the switch rate would have been identical. Many people would not have predicted that starting either [triple therapy or biologics] first would have been as good, radiographically or otherwise,” he says.

These findings are in line with another recently published study. A preliminary analysis from a big trial (called the TEAR study) found that at the end of two years, patients on triple therapy did as well as those on methotrexate plus etanercept. (In May, another analysis of the data from the TEAR study was published; Dr. O’Dell was the lead author of that study.)

What does this mean for patients? “If a patient is not doing well on one therapy, we should be switching to other therapies. Some of these work quicker than others and none of them works overnight, but all of them work over time,” Dr. O’Dell says.

The study results are potentially good news for patients who have shied away from biologics – either due to a fear of side effects or because of the cost of the drugs. The cost of triple therapy is considerably less than that of biologics, and the study found that certain side effects, including serious infections, were less severe.