TAC-TIC use of tacrolimus-based regimens in lupus nephritis

Abstract

Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN.

Efficacy of Cyclosporine in the Induction and Maintenance of Remission in a Systemic Lupus Erythematosus Patient Presenting with Macrophage-Activating Syndrome

“…Our patient was treated with low-dose cyclosporine (3 mg/kg/day) for 12 months without adverse events. On the other hand, tacrolimus, which is another calcineurin inhibitor, is more widely used for SLE than cyclosporine, particularly for those complicated with lupus nephritis [ 24 , 25 ]. However, it is unknown if tacrolimus would also be helpful for SLE-associated MAS.…”

Changing paradigms in the treatment of systemic lupus erythematosus

“…Recent observational studies have suggested that calcineurin inhibitors (CNI, that is, CsA and, mainly, TAC) may have equal or better efficacy than the aforementioned ‘first-line’ drugs, either when administered alone or as part of a ‘multitarget’ therapy combined with MMF (see ref 47 for a relevant meta-analysis). Moreover, a recent large RCT, including both phases of LN treatment (n=362 and 206 in induction and maintenance phase, respectively), found the combination of TAC with MMF to be superior to CYC in the induction phase (overall response rate at 6 months: 83.5% vs 63.0%, respectively, p<0.001) and equal to AZA for maintenance (similar relapse rate at 18 months: 5.47% vs 7.62%, respectively, with fewer adverse events in the multitarget arm) 48 49.…”

Lupus nephritis: An update on treatments and pathogenesis

“…We did encounter in one patient with CNI nephrotoxicity, and the patient had significant chronic kidney disease at baseline. A meta‐analysis showed that TAC‐containing regimens were associated with a higher efficacy and less leucopenia, but an increased risk of renal impairment . Voclosporin is a novel CNI with improved pharmacological characteristics that could result in more predictable pharmacokinetics and less variation between patients.…”

“…A meta-analysis showed that TAC-containing regimens were associated with a higher efficacy and less leucopenia, but an increased risk of renal impairment. 22 Voclosporin is a novel CNI with improved pharmacological characteristics that could result in more predictable pharmacokinetics and less variation between patients. Results from the Phase 2b AURA-LV study (NCT02141672) showed higher response rates with voclosporin compared with placebo, in combination with corticosteroids and MMF, at 24 and 48 weeks.…”