MYCOPHENOLATE MOFETIL VS TACROLIMUS IN PURE CLASS V LUPUS NEPHRITIS – A RANDOMISED COMPARATIVE STUDY

Introduction:

The consequences of the not-so benign class V membranous lupus nephritis (MLN) can be sinister and this entity needs to be dealt with promptly so as to prevent progression to chronic kidney disease. Currently, the most beneficial drugs for MLN are Mycophenolate Mofetil (MMF) and Tacrolimus with potentially few side effects but there are no major head-to-head trials comparing their efficacy, our objective is to arm ourselves with the best possible therapy, MMF or Tacrolimus in treatment of MLN.

Methods:

The study was a single-centre, open-label prospective case study conducted at IPGMER, Kolkata The study population underwent 1:1 randomisation at the start of study to receive MMF or Tacrolimus along with oral steroids. All patients received concomitant angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers (ACEIs/ARBs), statins and hydroxychloroquine. Patients received Tacrolimus at 0.075 mg/kg/day for first 6 months and MMF at a dose of 35 mg/kg/day and subsequently up-titrated or down-titrated as per requirement. All patients were evaluated at 6 months for evidence of complete remission. Tacrolimus dosage was titrated to maintain T0 at 6-10 ng/ml during first 6 months and at 4-6 ng/ml in the next 6 months after attaining complete remission. Oral steroids were tapered to 5mg/day by the end of 3 months. In patients achieving complete remission at 6 months, MMF and Tacrolimus was tapered and maintained at lowest possible dose for next 3 years. Those achieving partial response were continued on same therapy and dose for the next 6 months. Those not achieving any response at 6 months were subjected to a switch over according to standard protocol. Patients who had initially responded and subsequently relapsed on a particular drug were subjected to a switch over. At 6 months, protocol biopsy was undertaken if patients gave consent.  

Results:

At the start of the study, 30 patients were included, 15 patients in each arm. The baseline characters in both MMF and Tacrolimus arms were comparable. The mean age of the study population was 28.76 ± 8.28 years. After 6 months of induction therapy on either MMF or Tacrolimus, 21 patients achieved either complete remission (CR) or partial remission (PR); 9/15 in MMF arm and 12/15 in Tacrolimus arm. 6 patients who had MMF failure were switched to 6 months of induction therapy with Tacrolimus and achieved remission. 3 patients with Tacrolimus failure were switched over to induction therapy with MMF and all achieved remission. With time, both MMF and Tacrolimus arms showed significant reduction in proteinuria, MMF arm 57.1% decrease in mean proteinuria (p value <0.001) and Tacrolimus arm 71.9% decrease in mean proteinuria (p value <0.001). There was, however, faster resolution of proteinuria in patients in the Tacrolimus arm at 6 months of induction (p value 0.04) as shown in Figure 1. At the end of 6 months of induction therapy, and till 18 months of study period, there was significant difference in both groups as compared to baseline in terms of improvement in eGFR and SLEDAI- R. There was no mortality in either of the arms and none of the patients progressed to chronic kidney disease.

Conclusions:

Our study found that Tacrolimus was non-inferior to MMF in achieving remission, either complete or partial. Significantly faster resolution of proteinuria was seen in patients in the Tacrolimus arm compared to MMF arm. 

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.