Tacrolimus, a calcineurin inhibitor, appears to be an effective alternative to cyclophosphamide for initial treatment of lupus nephritis (LN) of any class, according to new study findings.
In a trial (ClinicalTrials.gov Identifier: NCT02457221), investigators randomly assigned 314 Chinese patients to receive oral tacrolimus (4 mg/d with dose adjustments) or intravenous cyclophosphamide (starting dose 0.75 g/m2 with dose adjustments) in addition to corticosteroids.
At 24 weeks, complete or partial response had occurred in 83.0% of the tacrolimus group compared with 75.0% of the cyclophosphamide group, a difference that was within the prespecified 15% noninferiority margin, Zhaohui Zheng, MD, of The First Affiliated Hospital of Zhengzhou University in China, and colleagues reported in JAMA Network Open. The investigators defined complete response as proteinuria of less than 0.5 g per 24 hours, serum albumin of 3.5 g/dL or greater, and serum creatinine in the reference range or within 15% of baseline value. They defined partial response as proteinuria of less than 3.5 g per 24 hours and decreased by more than 50% from baseline, serum albumin of 3.0 g/dL or greater, and stable kidney function.
Mean systemic lupus erythematosus disease activity index score (SLEDAI) also declined 8.6 and 6.4 points in the tacrolimus and cyclophosphamide group, respectively. No significant differences were observed between groups in serum complement 3 and 4 levels.
Mean 24-hour proteinuria improved significantly more with tacrolimus, the investigators reported. Least square mean change in 24-hour proteinuria from baseline was -4534.8 mg and -3632.5 mg in the tacrolimus and cyclophosphamide groups, respectively.
Serious treatment-emergent adverse events occurred in 18.5% of the tacrolimus group and 24.6% of the cyclophosphamide group. The most common serious drug-related adverse events were infections (mainly lung and upper respiratory tract infections): 8.9% vs 16.2%, respectively. Two patients died from a drug-related adverse event.
According to Dr Zheng’s team, “the findings from our study are encouraging for use of tacrolimus as LN initial therapy in clinical practice.”
Disclosure: This research was supported by Astellas Pharma China, Inc. Please see the original reference for a full list of disclosures.
Zheng Z, Zhang H, Peng X, et al. Effect of tacrolimus vs intravenous cyclophosphamide on complete or partial response in patients with lupus nephritis: a randomized clinical trial. JAMA Netw Open. Published online March 30, 2022. doi:10.1001/jamanetworkopen.2022.4492