Outcomes of maintenance therapy with tacrolimus versus azathioprine for active lupus nephritis: a multicenter randomized clinical trial

Abstract

Aim: The optimal maintenance therapy for active diffuse lupus nephritis remains to be established. In this study, we explored the efficacy and safety of tacrolimus for maintaining remission of active lupus nephritis compared to that of azathioprine. Methods: Seventy patients with biopsy-proven lupus nephritis who achieved remission were enrolled in nine nephrology centers in China from 2006 to 2008. Patients were randomized either to tacrolimus plus prednisone ( n = 34) or azathioprine plus prednisone ( n = 36) for six months. Tacrolimus was titrated to achieve a trough blood concentration of 4–6 ng/mL, and the dosage of azathioprine was 2 mg/kg/d. Prednisone was administered at a dose of 10 mg/d to both groups. The primary outcome was incidence of relapse. Response, clinical parameters and adverse effects were secondary endpoints. Results: After six months of therapy, two of the azathioprine-treated patients developed renal relapse compared to none of the tacrolimus-treated patients ( p = 0.49; odds ratio, 1.06; 95% CI (0.98, 1.15)). Leucopenia (defined as < 2000 cells per cubic millimeter) was significantly more frequent in the azathioprine group than the tacrolimus group (47% vs. 9%, p < .001). Conclusion: In conjunction with prednisone, maintenance therapy with tacrolimus and azathioprine has a similar low rate of renal relapse, and the tacrolimus regimen has a more favorable safety profile, with less leucopenia. However, since our study lacked sufficient power, longer follow-up is needed to draw final conclusions.

Mycophenolate as Maintenance Therapy for Lupus Nephritis with Impaired Renal Function

“…Finally, it is worth noting that renal relapses were recorded during therapy with MF in about 20% of the patients in most studies, as well as in ours. Therefore, other therapeutic schedules (based mainly on calcineurin inhibitors) have been tried, with promising results [14,17,27]. In fact, 4 patients in our study took other immunosuppressive drugs (3 calcineurin inhibitors and 1 rituximab) while taking MF; however, their low number prevented us from drawing solid conclusions about efficacy.…”

“…During the last decade, the results of at least 9 trials have been reported [8,9,11,12,13,14,15,16,17], and several retrospective studies [18,19,20] have focused on the best drug schedule in the maintenance phase of treatment of LN. The results allow us to conclude that short-term induction with intravenous CYC followed by maintenance therapy with MF or AZA was more efficacious than other treatment schedules [11,12,13,15].…”

Lupus Nephritis

“…Currently available clinical trials propound sequential therapy as an effective and safe alternative for treating severe LN in patients of white, Asian, African, or Hispanic ancestry (18)(19)(20)(21)(22)(23)(24)(25)(26). We have seen a comforting decline in CKD (7% or less) and mortality (10% or less) with the use of sequential therapies in the past two decades.…”

Steroid-sparing effect of tacrolimus in the maintenance phase of systemic lupus erythematosus: a single-center, prospective study

“…[17] Subsequently, several reports have noted the efficacy of TAC for nephritis. [18][19] [20] Maintenance therapy of SLE has been reported only in studies of patients with lupus nephritis or without lupus nephritis, [21][22] [23] and in a small group study and a short-duration study. [24][25] Thus, there have been no previous assessments of long-term TAC therapy in a larger group of SLE patients with/without nephropathy, as performed in this study.…”