Tacrolimus for the treatment of active rheumatoid arthritis: a systematic review and meta-analysis of randomized controlled trials

The aim of this study was to assess the efficacy and safety of tacrolimus in patients with active rheumatoid arthritis (RA).

We surveyed randomized controlled trials (RCTs) and open-label studies that examined the efficacy and toxicity of tacrolimus in disease-modifying anti-rheumatic drug (DMARD)--and methotrexate (MTX)-resistant or -intolerant patients with active RA patients using Medline, the Cochrane Controlled Trials Register, and by performing manual searches. Meta-analysis of RCTs was performed to determine treatment efficacy and safety outcomes. The results are presented as risk ratios (RRs), weighted mean differences (WMDs), or standardized mean differences (SMDs). Open-label studies were included in the systematic review.

The four RCTs included 1014 DMARD-resistant or -intolerant patients with DMARD-resistant or -intolerant RA. Median follow-up duration was 6 (range 4-6) months. American College of Rheumatology 20, 50, and 70% (ACR20, ACR50, and ACR70) response rates were significantly higher in the tacrolimus 3 mg/day group (n = 390) than in the controls (n = 402) [primary efficacy outcome, ACR50; risk ratio (RR) 2.583, 95% confidence interval (CI) 1.095-6.092, p = 0.030], and efficacies in the tacrolimus 1.5-2 mg/day group showed a similar pattern. Patients treated with tacrolimus withdrew from treatment because of adverse events (n = 222) (primary safety outcome, withdrawals due to adverse events; RR 1.475, 95% CI 0.895-2.187, p = 0.053) more frequently than controls (n = 231), although this was not significant. All four open-label studies found that tacrolimus was safe, well-tolerated, and provided clinical benefits.

Tacrolimus, at dosages of 1.5-3 mg/day, was found to be effective in DMARD-resistant or -intolerant patients with active RA.