His larger question, though, was whether biologics perform better than synthetic disease-modifying agents.
In the IDEA study, patients were randomized to receive methotrexate plus the anti–tumor necrosis factor (TNF) drug infliximab (Remicade) or methotrexate plus IV methylprednisolone. After 26 weeks in both arms, if DAS 28 scores were 2.4 or lower, the therapy was continued at current doses; if higher, it was escalated.8 The study found that the two arms performed similarly.
“Treat to target is effective in early disease—rapid and sustained remission can be achieved by both ways, but obviously this [the nonbiologic approach] is the more affordable way,” said Dr. Smolen. But he also noted that 15% of patients, whose disease activity remained high after 26 weeks, were switched from nonbiologic therapy to biologic, and benefited.
In the SWEFOT trial, patients were started on methotrexate and, if they still had moderate to high disease activity after three months, were switched to either conventional triple therapy (sulfasalazine, hydroxychloroquine, and methotrexate) or infliximab.9 There were advantages in the infliximab arm after a year, but after two years, “these differences were not apparent,” Dr. Smolen said. “Neither clinical nor radiologic.”
The results aren’t easily interpreted, he said. One take-home message might be that traditional therapy can yield similar results to infliximab if it is sustained long enough. On the other hand, Dr. Smolen said, 24 of 130 patients had to withdraw from the conventional arm because of lack of efficacy, while just 5 of 128 dropped out from the biologic arm due to lack of efficacy.
Dr. Smolen called the TEAR study “one of the most complex clinical trials he’s seen in recent years—or ever.” The study started with two pairs of arms. The first pair included a conventional triple-therapy arm and a methotrexate-plus-etanercept arm. The second pair included subjects who all started on methotrexate then, if their disease activity was moderate to high, were switched to either standard triple therapy or etanercept.
Those in the etanercept arms collectively were more likely to have profound effects, with a higher percentage of ACR70 response rates and better radiographic outcomes, but the overall performance was similar in both the biologic and nonbiologic arms. Dr. Smolen also had doubts about the power of this study, because the dropout rate was much higher than anticipated.
Dr. Smolen said a major question among rheumatologists is how biologics compare.
In the AMPLE trial, immunomodulator abatacept plus methotrexate was compared with TNF-inhibitor adalimumab plus methotrexate in patients with active disease, and there was overall a very close similarity in this analysis.10