Eighteen RCTs (n=2,148: 1,109 receiving treatment and 1,039 controls) were included in the review. The sample sizes ranged from 6 to 315 participants.
Three studies scored 5 on the Jadad scale, but the majority scored 3 (72%).
Participants receiving the intervention reported significantly greater benefit compared with controls (OR 0.35, 95% CI: 0.25, 0.49, p=0.00001). Tumour necrosis factor (TNF) inhibitors (4 RCTs) and gold salts (2 RCTs) were shown to have the greatest treatment effect, while sulfasalazine (4 RCTs) and leflunomide (1 RCT) reported moderate effect sizes. One RCT of methotrexate was terminated early and it was not possible to report on the remaining 6 studies as no events occurred.
The intervention group reported a significantly higher number of withdrawals compared with controls (OR 2.33, 95% CI: 1.61, 3.37, p=0.00001), with the most significant differences being reported for patients treated with leflunomide (1 RCT) and gold salts (2 RCTs), and a relatively high withdrawal rate with sulfasalazine (5 RCTs). The number of withdrawals in the TNF inhibitors group compared with controls was not significantly different (4 studies).
Sensitivity analyses did not significantly alter the results. There was no significant heterogeneity among studies for the overall pooled result for either outcome. Treatment with TNF inhibitors reported the most benefit when using the NNT:NNH ratio.