Aims This study aimed to evaluate the efficacy and safety of calcineurin inhibitors (CNIs), cyclosporine (CSA), and tacrolimus (TAC) in patients with active rheumatoid arthritis (RA) based on randomized controlled trials (RCTs). Methods A systematic literature search of PubMed, the Cochrane Library, and EMBASE was conducted to identify RCTs comparing CSA and TAC with placebo in RA. Outcomes included American College of Rheumatology (ACR) responses, assessments of tender and swollen joint counts, inflammatory markers, global assessments, and safety endpoints. The primary efficacy outcome was the ACR20 response rate, and the primary safety outcome was the mean increment in serum creatinine (s‐Cr). Subgroup analyses were performed to assess dose‐dependent effects. Results Eleven RCTs (7 CSA, 4 TAC) including 1793 patients were analyzed. Both CSA (RR 1.559, 95% CI 1.099; 2.213, p = 0.013) and TAC (RR 2.139, 95% CI 1.769; 2.586, p < 0.001) significantly improved ACR20 response rates compared to placebo. Secondary efficacy outcomes showing significant differences from placebo were more frequently observed in TAC than in CSA. TAC showed less dose‐dependence, whereas CSA showed a more dose‐dependent trend. Regarding safety, CSA was associated with dose‐dependent increases in s‐Cr and secondary safety outcomes. TAC showed a mild but consistent increase in s‐Cr regardless of dose, and no significant increase in secondary safety outcomes was observed at lower doses. At lower doses, both drugs maintained efficacy and were associated with fewer adverse events (AEs). Conclusions CSA and TAC were effective in patients with RA who had an inadequate response to disease‐modifying antirheumatic drugs. Both drugs maintained efficacy and were associated with fewer AEs at lower doses. These findings provide context for considering lower‐dose CNI regimens in selected patient populations. However, concerns about long‐term safety remain, and further long‐term studies are needed to clarify the role of CNIs in the treatment of RA.
Kim et al. (Thu,) studied this question.