Four randomised controlled trials, with 515 participants, were identified. Three trials were double-blind and placebo-controlled; one trial was single-blind. The loss to follow-up ranged from 5 to 28%, and the length of follow-up was from 24 to 52 weeks.
In the two trials of treatment of patients naive to sulfasalazine and methotrexate, the Disease Activity Score (DAS) effect sizes for the combination therapy compared with methotrexate alone were 0.2 (95% CI -0.3 to 0.7) and 0.3 (95% CI 0.1 to 0.8), and for the combination therapy compared with sulfasalazine alone were 0.3 (95% CI -0.2 to 0.8) and 0.1 (95% CI -0.2 to 0.4).
For the two trials that included sulfasalazine treatment-failure patients, the effect sizes for combination therapy were 1.8 (95% CI 1.0 to 2.5) and 0.5 (95% CI 0.1 to 0.9) compared to methotrexate alone, and 0.5 (95% CI 0.1 to 0.9) for sulfasalazine alone.
The proportion of patients fulfilling ACR 20, 50 and 70% responses were also reported in two trials. One trial was of treatment-naive patients and the other trial was of patients who failed to respond to sulfasalazine. In four of the six data sets from these two trials, the response rates were higher in the combination therapy group compared with either treatment alone.
Significantly more nausea was reported with the combination therapy in the two trials of patients naive to treatment.