Low dose mycophenolate mofetil versus cyclophosphamide in the induction therapy of lupus nephritis in Nepalese population: a randomized control trial

Abstract

Background: The management of proliferative lupus nephritis (LN) comprises timely and coordinated immunosuppressive therapy. This study aimed to evaluate and compare the effectiveness and safety profile of low dose mycophenolate mofetil (MMF) and cyclophosphamide (CYC) in induction therapy of LN in Nepalese population.

Methods: We conducted a prospective, open-label, randomized trial over a period of one and half years. Forty-nine patients with class III to V lupus nephritis were enrolled, out of which 42 patients (21 in each group) could complete the study. CYC was given intravenously as a monthly pulse and MMF was administered orally in the tablet form in the maximum daily dose of 1.5 g in two divided doses.

Results: The mean age of the patients was 25.43 ± 10.17 years with female to male ratio of 7.3:1. Mean baseline serum creatinine was 1.58 ± 1.38 mg/dL and eGFR was 62.38 ± 26.76 ml/min/1.73m2. Mean 24-h urinary protein was 4.35 ± 3.71 g per 1.73 m2 body surface area. At 6 months, serum creatinine (mg/dL) decreased from 1.73 to 0.96 in CYC and from 1.24 to 0.91 in the MMF group with improvement in eGFR (ml/min/1.73 m2) from 60.33 to 88.52 in CYC and from 64.42 to 89.09 in MMF group. Twenty-four-hour urinary protein (gm/1.73m2) reduced from 4.47 to 0.94 in CYC and from 4.5 to 0.62 in the MMF group. Primary end point was achieved in higher percentage of patients with MMF than CYC (28.6% vs. 19%) while equal proportion of patients (67% in each group) achieved secondary end point in both groups. Number of non-responders was higher in CYC group than in the MMF group (14.3% vs. 4.8%). There was no difference in the rate of achievement of secondary end point in both CYC and MMF groups (3.16 vs. 3.05 months). The occurrence of adverse events was higher in the CYC than in MMF group (56 vs. 15 events).

Conclusion: Present study has concluded that MMF, used in relatively lower dose, is equally effective in inducing remission with reduction of proteinuria and improvement of kidney function with lesser adverse events than CYC in the induction therapy of proliferative lupus nephritis.

Trial registration: Retrospectively registered to ClinicalTrials.gov PRS. NCT03200002 (Registered date: June 28, 2017).

Keywords: Cyclophosphamide; Induction therapy; Lupus nephritis; Mycophenolate mofetil.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval was obtained from the Institutional Review Board of National Academy of Medical Sciences (NAMS), Kathmandu, Nepal. Patients gave informed written consent to participate in the study. Written informed consent was also obtained from the parents of the participants below 18 years of age.

Consent for publication

Not applicable.

Competing interests

AS is employed by Chitwan Medical College and does not have financial benefits in participating in the study.

RH, RKA and AB are employed by the Government of Nepal and currently posted at National Academy of Medical Sciences and have not received any financial benefits for getting involved in the study.

GRB is employed by UnitedHealth Group and also owns company stocks. No financial benefits are received in participating in this study.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1

Flowchart showing patient randomization and follow-up. SLE- Systemic lupus erythematosus, LN- Lupus Nephritis, ACR- American college of rheumatology, CYC- cyclophosphamide, MMF- mycophenolate mofetil

Fig. 2

Changes in serum creatinine, serum albumin and 24-h proteinuria and achievement of secondary end point over the 6-month induction period. Serum creatinine expressed in mg/dL, 24-h proteinuria expressed in gram/day, serum albumin expressed in gram per dL and achievement of secondary end point in numbers. CYC- cyclophosphamide, MMF- Mycophenolate mofetil. a Change in serum creatinine. b Change in 24-h proteinuria. c Change in serum albumin. d Achievement of secondary end point