The TEAR trial, which I participated in, was a trial to try to determine if a delay in triple therapy—which is hydroxychloroquine/sulfasalazine/methotrexate—or delay in a biologic therapy—in this particular example, etanercept/methotrexate—would have a long-term impact on the outcomes of patients with rheumatoid arthritis, in comparison to starting those drugs right in the beginning. And, there are certain centers in the country that feel triple therapy is as effective as biologic therapy plus methotrexate, and indeed, most of the data do support that.
Most rheumatologists feel more comfortable with a biologic plus methotrexate rather than triple therapy, but the work done by Larry Moreland, Jim O’Dell, and others does show, in this study, that triple therapy is quite effective. So, this was a study looking at people with very early rheumatoid arthritis—about 3 to 4 months of disease—in 755 patients. They were seropositive, rheumatoid factor or CCP antibody, or they had at least 2 erosions on x-rays. And, they had very active disease: baseline disease activity scores were 5.7 or 5.8. And there were 4 treatment groups. We initially had etanercept/methotrexate, sulfasalazine/Plaquenil (hydroxychloroquine)/methotrexate, and then actually, a third group, which was methotrexate by itself.
At the end of 6 months, those patients who were not in low disease activity, as measured by a DAS score, had their therapy escalated. About 28% of patients on methotrexate alone—as we talked about, 30% of people on methotrexate do achieve low-disease activity—achieved low-disease activity. And, in the first 6 months, patients on etanercept/methotrexate or triple therapy did better than the patients on methotrexate alone. From month 6 to month 24, the patients who still had active disease on methotrexate alone were escalated, in a blinded fashion, to either etanercept/methotrexate or triple therapy. At the end of 24 months, there was no difference in the clinical outcome between the 4 groups.
The delayed starters at 6 months escalated to therapy. The disease activity scores had improved by the same degree. So, from a clinical standpoint, what this showed is that triple therapy was as effective as etanercept/methotrexate, and clearly less expensive—so that’s a real bonus for those people who can’t afford biologics. The delay of 6 months had no impact on quality of life, as measured by HAQ scores and SF-36s, which can measure disability, physical function, mental function, and also just the classical examinations: joint counts, acute phase reactants—ACR responses—and so forth. There were some subtle differences; there was slightly more x-ray progression in the triple therapy group compared to the biologic group. And the more robust responses at week 24, the ACR70 responses, favored the etanercept group.
The take-home message is that triple therapy is effective. In most patients, it will work as effectively as a biologic with methotrexate. Another study by the same group, the RACAT study, showed a similar phenomenon: that triple therapy was seen to be as effective as etanercept/methotrexate. Many of us believe that the retention on triple therapy is not as good as the retention on biologics, but we don’t have those objective data. So, I think these are 2 very good treatment options. It’s a very important study that’s showing there’s no harm to the patient if you delay therapy 6 months and just use methotrexate alone—not delay therapy, but delay more aggressive therapy—and that the triple therapy is as effective.