Induction Therapy for Pediatric Focal Proliferative Lupus Nephritis: Cyclophosphamide Versus Mycophenolate Mofetil

Background: Intravenous cyclophosphamide (IVCY) concomitant with corticosteroids demonstrated better outcomes in therapy of proliferative lupus nephritis albeit adverse effects may occur. Mycophenolate mofetil (MMF) is a newer oral medication for treating lupus nephritis. Objective: To compare renal outcomes between IVCY and MMF in conjunction with corticosteroid for induction therapy of proliferative lupus nephritis. Materials and Methods: The authors reviewed the medical records from four university hospitals of children who received prednisolone with either MMF or IVCY for induction therapy of proliferative lupus nephritis between 2005 and 2014 in the present retrospective cohort study. Results: Twenty-eight and 85 patients were included in the MMF and IVCY group, respectively. The respective mean age at MMF and IVCY initiation was 12.36±2.87 and 11.84±3.04 years. Renal remission was not significantly different between the groups (p=0.690). Non-nephrotic range proteinuria (adjusted OR 2.93, 95% CI 1.23 to 6.94, p=0.015), and high initial GFR (adjusted OR 2.93, 95% CI 1.14 to 7.56, p=0.026) were significantly associated with achieving renal remission. Both infectious (82.1%) and non-infectious complications (96.9%) were more common in the IVCY group. Neither death nor end-stage renal disease (ESRD) occurred during the induction therapy. Conclusion: There was no significant difference in renal remission whether children received MMF or IVCY for induction therapy of lupus nephritis; however, adverse events occurred less frequently in the MMF group. Keywords: Children, Lupus nephritis, Systemic lupus erythematosus, Mycophenolate, Cyclophosphamide, Induction

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Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis

Nephrology ◽

10.1111/j.1440-1797.2005.00444.x ◽

2005 ◽

Vol 10 (5) ◽

pp. 504-510 ◽

Cited By ~ 160

Author(s):

LOKE MENG ONG ◽

LAI SEONG HOOI ◽

TECK ONN LIM ◽

BAK LEONG GOH ◽

GHAZALI AHMAD ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Induction Therapy ◽

Controlled Trial ◽

Intravenous Cyclophosphamide ◽

Randomized Controlled ◽

Proliferative Lupus Nephritis

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Lupus Nephritis: Induction Therapy

Lupus ◽

10.1191/0961203305lu2114oa ◽

2005 ◽

Vol 14 (3_suppl) ◽

pp. 27-32 ◽

Cited By ~ 3

Author(s):

TM Chan

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Adverse Effects ◽

Induction Therapy ◽

Chinese Patients ◽

Renal Outcome ◽

Induction Treatment ◽

Renal Survival ◽

Proliferative Lupus Nephritis

Effective induction therapy is of pivotal importance in minimizing renal parenchymal damage by the active immune-mediated inflammatory processes in severe proliferative lupus nephritis. Preservation of nephron mass is prerequisite to long-term renal survival. Data from US-based studies have shown improved efficacy with induction treatment comprising corticosteroid and cyclophosphamide, compared with corticosteroid treatment alone. Data from European studies have shown similar efficacy with a modified treatment regimen, in which smaller doses of cyclophosphamide were given at weekly or fortnightly intervals over a shortened treatment duration, and the treatment related adverse effects appeared less frequent with the reduced-dose regimen. We have also reported that sequential immunosuppression with prednisolone and oral cyclophosphamide as induction followed by azathioprine maintenance was associated with a high incidence of remission and relatively favourable long-term renal outcome in Chinese patients. However, cyclophosphamide treatment is associated with considerable adverse effects, which could be potentially fatal. Mycophenolate mofetil selectively inhibits lymphocyte proliferation, and thus targets an instrumental step in the pathogenesis of systemic lupus erythematosus. There is accumulating evidence that the combined use of mycophenolate mofetil and corticosteroid presents an effective treatment for severe proliferative lupus nephritis in different ethnic groups, and is associated with much fewer adverse effects compared with cyclophosphamide-based regimens. Recent data from our group also demonstrate the long-term efficacy of mycophenolate mofetil in preserving renal survival, when used continuously as both induction and maintenance therapy.

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Is mycophenolate mofetil superior to pulse intravenous cyclophosphamide for induction therapy of proliferative lupus nephritis in Egyptian patients?

Clinical and Experimental Nephrology ◽

10.1007/s10157-010-0270-7 ◽

2010 ◽

Vol 14 (3) ◽

pp. 214-221 ◽

Cited By ~ 25

Author(s):

Eid M. El-Shafey ◽

Said H. Abdou ◽

Mohamed M. Shareef

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Induction Therapy ◽

Intravenous Cyclophosphamide ◽

Proliferative Lupus Nephritis ◽

Egyptian Patients

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Long-term follow-up of the MAINTAIN Nephritis Trial, comparing azathioprine and mycophenolate mofetil as maintenance therapy of lupus nephritis

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2014-206897 ◽

2015 ◽

Vol 75 (3) ◽

pp. 526-531 ◽

Cited By ~ 68

Author(s):

Farah Tamirou ◽

David D'Cruz ◽

Shirish Sangle ◽

Philippe Remy ◽

Carlos Vasconcelos ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Positive Predictive Value ◽

Maintenance Therapy ◽

Early Response ◽

Renal Outcome ◽

Proliferative Lupus Nephritis ◽

Long Term Follow Up

ObjectiveTo report the 10-year follow-up of the MAINTAIN Nephritis Trial comparing azathioprine (AZA) and mycophenolate mofetil (MMF) as maintenance therapy of proliferative lupus nephritis, and to test different definitions of early response as predictors of long-term renal outcome.MethodsIn 2014, data on survival, kidney function, 24 h proteinuria, renal flares and other outcomes were collected for the 105 patients randomised between 2002 and 2006, except in 13 lost to follow-up.ResultsDeath (2 and 3 in the AZA and MMF groups, respectively) and end-stage renal disease (1 and 3, respectively) were rare events. Time to renal flare (22 and 19 flares in AZA and MMF groups, respectively) did not differ between AZA and MMF patients. Patients with good long-term renal outcome had a much more stringent early decrease of 24 h proteinuria compared with patients with poor outcome. The positive predictive value of a 24 h proteinuria <0.5 g/day at 3 months, 6 months and 12 months for a good long-term renal outcome was excellent (between 89% and 92%). Inclusion of renal function and urinalysis in the early response criteria did not impact the value of early proteinuria decrease as long-term prognostic marker.ConclusionsThe long-term follow-up data of the MAINTAIN Nephritis Trial do not indicate that MMF is superior to AZA as maintenance therapy in a Caucasian population suffering from proliferative lupus nephritis. Moreover, we confirm the excellent positive predictive value of an early proteinuria decrease for long-term renal outcome.Trial registration numberNCT00204022.

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EFFECT OF MYCOPHENOLATE MOFETIL THERAPY COMBINED WITH PREDNISONE FOR THE TREATMENT OF PROLIFERATIVE LUPUS NEPHRITIS

JCR Journal of Clinical Rheumatology ◽

10.1097/01.rhu.0000226660.59688.86 ◽

2006 ◽

Vol 12 (Supplement) ◽

pp. S64

Author(s):

H Esteva-Spinetti ◽

Mar??a Camargo-Duque ◽

Eylen M. Serrano Casas ◽

C Juan ◽

Sandra Romero-Aguaida

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Proliferative Lupus Nephritis

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Comparing the Efficacy and Safety of Induction Therapies for the Treatment of Patients with Proliferative Lupus Nephritis in South Africa

International Journal of Nephrology ◽

10.1155/2020/2412396 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Phelisa Sogayise ◽

Udeme Ekrikpo ◽

Ayanda Gcelu ◽

Bianca Davidson ◽

Nicola Wearne ◽

...

Keyword(s):

South Africa ◽

Lupus Nephritis ◽

Induction Therapy ◽

Randomized Study ◽

Induction Treatment ◽

Limited Data ◽

Proliferative Lupus Nephritis ◽

Significant Difference ◽

Kidney Replacement Therapy

Background. Lupus nephritis (LN) can be complicated with requirement for kidney replacement therapy and death. Efficacy of induction therapies using mycophenolate mofetil (MMF) or intravenous cyclophosphamide (IVCYC) has been reported from studies, but there is limited data in Africans comparing both treatments in patients with proliferative LN. Methods. This was a retrospective study of patients with biopsy-proven proliferative LN diagnosed and treated with either MMF or IVCYC in a single centre in Cape Town, South Africa, over a 5-year period. The primary outcome was attaining complete remission after completion of induction therapy. Results. Of the 84 patients included, mean age was 29.6 ± 10.4 years and there was a female preponderance (88.1%). At baseline, there were significant differences in estimated glomerular filtration rate (eGFR) and presence of glomerular crescents between both groups ( p ≤ 0.05 ). After completion of induction therapy, there was no significant difference in remission status (76.0% versus 87.5%; p = 0.33 ) or relapse status (8.1% versus 10.3%; p = 0.22 ) for the IVCYC and MMF groups, respectively. Mortality rate for the IVCYC group was 5.5 per 10,000 person-days of follow-up compared to 1.5 per 10,000 person-days of follow-up for the MMF group ( p = 0.11 ), and there was no significant difference in infection-related adverse events between both groups. Estimated GFR at baseline was the only predictor of death (OR: 1.0 [0.9–1.0]; p = 0.001 ). Conclusion. This study shows similar outcomes following induction treatment with MMF or IVCYC in patients with biopsy-proven proliferative LN in South Africa. However, a prospective and randomized study is needed to adequately assess these outcomes.

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