Cyclophosphamide Versus Mycophenolate Mofetil in Lupus Nephritis
Cyclophosphamide Versus Mycophenolate Mofetil in Lupus Nephritis
This was a prospective open label randomized control trial, which was conducted for a period
 of one and half year from January 2014 to June 2015. Out of 52 patients screened, 49 patients
 meeting the international society of nephrology/ renal pathology society (ISN/RPS) criteria
 were enrolled in the study comprising of 25 and 24 patients in the cyclophosphamide (CYC) and
 mycophenolate mofetil (MMF) groups respectively. Forty two patients (21 in each group) could
 complete the study till the end of 6 months and were included in final analysis. Baseline
 clinical evaluation and investigations were done and recorded. CYC was given intravenously as
 a monthly pulse in the dose of 0.5 to 1 gram per m2 body surface area. MMF was administered
 in the tablet form with the starting dose of 500 mg twice daily, which was increased to 750
 mg twice daily after a month. Patients were assessed and monitored monthly and the details
 were recorded. Efficacy of treatment was measured as primary end point for those who achieved
 partial remission (reduction of 24 hour urinary protein to < 3.5gms/day if baseline
 proteinuria >3.5 gms/day or decrease by 50% if baseline proteinuria <3.5 gms/day) and
 secondary end point for those who achieved complete remission (normalization of serum
 creatinine and < 500 mg of 24 hour urinary protein). Adverse events experienced by the
 patients were also recorded during monthly visit.
Systemic lupus erythematosus (SLE) is an autoimmune disease associated with multiple organ
 involvement, among which kidney involvement, also known as lupus nephritis (LN), is quite
 common in SLE. LN is associated with a more than four-fold increase in mortality in patients
 with SLE. The management of SLE and LN comprises timely and coordinated management consisting
 of initial or induction phase of aggressive immunosuppression to bring the active disease
 under control followed by maintenance phase. The initial phase usually lasting for six months
 consists of treatment with steroid and cyclophosphamide or mycophenolate mofetil. So far
 there is no study published regarding the efficacy and adverse events of such treatments in
 Nepal. So, this study aimed to evaluate and compare the effectiveness and safety profile of
 mycophenolate mofetil and intravenous pulse cyclophosphamide in induction therapy of LN in
 Nepalese population.

 A total of 52 patients with international society of Nephrology/ renal pathology society
 (ISN/RPS) class III to V lupus nephritis were screened, 3 of which did not meet entry
 criteria and 49 patients were enrolled in the study comprising of 25 and 24 patients in the
 MMF and CYC group respectively. Twenty one patients in each groups could complete the study
 till the end of 6 months and were included for analysis.

 Patients in the CYC group received intravenous cyclophosphamide (CYC) in the dose of 0.5 to 1
 gram per m2 of body surface area. The medicine, which is available in the strength of 1 gram
 in powder form, was first dissolved in 20 ml of normal saline. Only15 ml of this preparation
 was mixed in 100 ml of normal saline and was infused over a period of one hour. CYC was not
 given to those patients who had total leukocyte counts (TLC) less than 2500/mm3. Those
 patients were re-evaluated after one week and intravenous pulse CYC was reinstituted if the
 total leucocyte count (TLC) exceeds 2500/mm3. Pulse CYC was administered every month for a
 total of six infusions.Patients were monitored monthly and the details were recorded. During
 follow ups, any adverse events in between were noted and detailed physical evaluation was
 done and all baseline investigations (except USG abdomen, chest X-ray, serum anti nuclear
 antibody (ANA) and anti double strain deoxy-ribonuccleic acid (anti dsDNA), complement factor
 3 (C3) and complement facotr 4 (C4) level) was repeated. Fasting lipid profile was repeated
 at the end of third and sixth month of treatment.

 During the course of treatment, if a patient had interruption of medication for less than a
 10 days' period due to any reason, s/he was considered as a regularly included subject. If
 the interruption extended beyond 10 days, the patient was withdrawn from the study.

 Patients in the MMF group were administered tablet mycophenolate mofetil at a starting dose
 of 500 mg twice daily if the weight of the patient was less than 50 kilograms and 750 mg
 twice daily if the weight was more than 50 kilograms. After one month, the dose of MMF was
 increased to 750 mg twice daily. The clinical response was monitored in terms of reduction in
 serum creatinine and proteinuria. MMF dose was decreased or interrupted in patients
 experiencing an absolute neutrophil count <1300/mm3 at any study visit; MMF treatment was
 discontinued if a patient experienced an absolute neutrophil count <1000/mm3.

 All patients, irrespective of randomized group, received concomitant corticosteroid therapy
 with oral prednisolone and hydroxychloroquine. Angiotensin receptor inhibitors (ACEi)/
 angiotensin receptor blocker (ARBs) were given to all patients if the blood pressure remained
 above or equal to 120 mmHg of systolic blood pressure and 80 mmHg of diastolic blood
 pressure. If the blood pressure remained persistently high despite the use of ACEi/ARBs,
 other antihypertensives were added as required to achieve target blood pressure <130/80 mmHg.
 Oral prednisolone was given at an initial dose of 1 mg/kg with a maximum dose of 60 mg/day.
 The starting dose of prednisolone was continued for initial one month. Then, the dose of oral
 prednisolone was tapered at the rate of 10 mg/day every 2 weeks and was maintained at the
 baseline dose of 5 to 7.5 mg per day then after. Additional intravenous methylprednisolone
 was given at the beginning of treatment for patients who presented as rapidly progressive
 glomerulonephritis (RPGN) and who had activity index of more than 8 out of 24 on kidney
 biopsy irrespective of the randomized group (MMF or CYC) of the patient. The dose of
 methylprednisolone was 1 gram, which was given after mixing with 100 ml of normal saline and
 was infused intravenously over 1 hour for 3 days.
Inclusion Criteria:

 -  Newly diagnosed LN with ISN/RPS histopathology classes III to V

 Exclusion Criteria:

 -  Patients with biopsy had proven ISN / RPS classes I, II and VI LN

 -  Patients with previous history of treatment and relapse of lupus nephritis

 -  Patients who were receiving continuous dialysis for more than two weeks prior to
 randomization.

 -  Patients of less than 12 years of age

 -  Patients who had concurrent infection or illness at the time of enrollment

 -  Patients who were taking concurrent medications which are supposed to have
 interactions with MMF or CYC

 -  Female patients who were pregnant and breastfeeding.

 -  Patients who did not give consent for participation