For patients with an inadequate response to MTX, both triple therapy with MTX, sulfasalazine, and hydroxychloroquine and the addition of a targeted biologic agent to MTX are effective treatment options. The RACAT study, a 48-week, randomized, double-blind, noninferiority trial, compared triple therapy with treatment with etanercept and MTX in patients who were inadequately responsive to MTX monotherapy. Both treatment groups experienced significant improvement in clinical outcomes. Switching to the alternative treatment regimen was required in 27% of patients in each group at 24 weeks, and both groups achieved improvement in disease activity with the alternative therapy.

An advantage of triple therapy is that it is less costly than the addition of a targeted biologic agent to MTX; however, the number of pills that a patient must take on a daily basis for triple therapy presents a substantial inconvenience compared with the combination of weekly MTX and weekly to monthly tumor necrosis factor inhibitor (TNFi) dosing. This results in a higher rate of treatment discontinuation among those receiving triple therapy compared with those receiving a TNFi and MTX. In a retrospective analysis of patients with rheumatoid arthritis enrolled in the Corrona registry, 97% of patients were treated with the combination of a TNFi and MTX, whereas only 3% were taking triple therapy. Additionally, patients receiving triple therapy were significantly more likely to discontinue treatment compared with those receiving a TNFi and MTX. Thus, although the cost of treatment with triple therapy may be lower than that of the combination of a targeted biologic agent and MTX, the long-term benefits of triple therapy may be less. I believe that the most important consideration when choosing a treatment regimen should be its potential benefit to the patient.