Addition of cyclosporine/tacrolimus for pediatric relapsed lupus nephritis during mycophenolate mofetil maintenance therapy

Objective We aimed to evaluate the efficacy of low-dose cyclosporine (CsA) or tacrolimus (Tac) in children with proliferative lupus nephritis (PLN) during maintenance therapy. Methods A low dose of CsA or Tac was added to 11 children who relapsed during mycophenolate mofetil (MMF) maintenance therapy. Renal remission was analyzed at 3 and 6 months, and at 1, 2, and 3 years after CsA/Tac addition. Adverse effects were recorded. Results The clinical response rates were 81.9%, 100%, 90.0%, 100%, and 100% at 3 months, 6 months, 1 year, 2 years, and 3 years after CsA/Tac addition, respectively. Complete renal remission rates were 45.5%, 45.5%, 40.0%, 44.4%, and 71.4% at 3 months, 6 months, 1 year, 2 years, and 3 years after CsA/Tac addition, respectively. None of the patients had severe adverse events. Conclusion Low-dose CsA/Tac combined with MMF shows a promising effect in renal remission with acceptable safety in children with PLN. Therefore, this combination would be a good choice for children with lupus nephritis who relapse or have suboptimal MMF maintenance therapy.

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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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Comparison between high-dose, low-dose cyclophosphamide and mycophenolate mofetil in treatment of proliferative lupus nephritis (an Egyptian multicenter retrospective study)

Journal of The Egyptian Society of Nephrology and Transplantation ◽

10.4103/jesnt.jesnt_13_21 ◽

2021 ◽

Vol 21 (4) ◽

pp. 174

Author(s):

RashaA. Abdel Noor ◽

Mervat Eissa ◽

HanaaI Okda ◽

HendH Abdelnabi ◽

SaharA Ahmed ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Retrospective Study ◽

Lupus Nephritis ◽

Low Dose ◽

High Dose ◽

Proliferative Lupus Nephritis

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Maintenance Therapies for Proliferative Lupus Nephritis: Mycophenolate Mofetil, Azathioprine and Intravenous Cyclophosphamide

Lupus ◽

10.1191/0961203305lu2115oa ◽

2005 ◽

Vol 14 (3_suppl) ◽

pp. 33-38 ◽

Cited By ~ 26

Author(s):

G Contreras ◽

E Tozman ◽

Nilay Nahar ◽

David Metz

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Treatment Failure ◽

Low Dose ◽

Cumulative Probability ◽

High Dose ◽

Short Term ◽

Proliferative Lupus Nephritis ◽

Severe Infections

For the treatment of proliferative lupus nephritis, long-term cyclophosphamide (CY) regimens are efficacious, however, at the expense of substantial toxicity. In the last decade, sequential regimens of short-term CY induction followed by either mycophenolate mofetil (MMF) or azathioprine (AZA) maintenance have shown to be efficacious and safe reducing the long-term exposure to CY. In a maintenance study including predominantly Hispanics and African-Americans, the patients who received MMF and AZA maintenance had a higher cumulative probability of remaining free of the composite of death or chronic renal failure (CRF) compared to quarterly intravenous CY (IVCY) maintenance (89% in MMF, 80%, in AZA and 45% in IVCY). Likewise, MMF and AZA maintenance were associated with significantly lower incidence of severe infections (2% in each MMF or AZA, and 25% in IVCY), sustained amenorrhea (6% in MMF, 8% in AZA, and 32% in IVCY), and hospitalizations (one hospital-days per patient-year in each MMF or AZA, and 10 in IVCY). In a European induction study including predominantly Caucasians, patients who received any of two sequential regimens, low dose versus high dose IVCY induction both followed by AZA maintenance, had a high cumulative probability of remaining free of treatment failure (84% in low dose IVCY and 80% in high dose IVCY; treatment failure defined as a composite of free of corticosteroid resistant flare, nephrotic syndrome, doubling creatinine, and persistent elevated creatinine). Low dose IVCY and high dose IVCY induction were associated with low incidence of sustained amenorrhea (4% in each group) and severe infections (11% in low dose and 22% in high dose IVCY induction). Of interest, most of the severe infection episodes occurred while patients were receiving IVCY induction. Finally an Asian study demonstrated that patients with proliferative lupus nephritis could be effectively treated with short-term oral CY induction followed by AZA maintenance. The cumulative probability of complete remission was 76%. The relapse rate was only 11%. The incidence of permanent amenorrhea and infection were 8% and 33%, respectively. None of the Asian patients had an increase in serum creatinine level to double the baseline value. Maintenance therapies with MMF or AZA following short-term CY induction in a sequential regimen are efficacious and safe for the treatment of high-risk patients with proliferative lupus nephritis.

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Mycophenolate mofetil as maintenance therapy for proliferative lupus nephritis: a long-term observational prospective study

Arthritis Research & Therapy ◽

10.1186/ar3184 ◽

2010 ◽

Vol 12 (6) ◽

Cited By ~ 12

Author(s):

Katerina Laskari ◽

Clio P Mavragani ◽

Athanasios G Tzioufas ◽

Haralampos M Moutsopoulos

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Maintenance Therapy ◽

Prospective Study ◽

Observational Prospective Study ◽

Proliferative Lupus Nephritis

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Maintenance therapy with mycophenolate mofetil for children with severe lupus nephritis after low-dose intravenous cyclophosphamide regimen

Pediatric Nephrology ◽

10.1007/s00467-008-0800-7 ◽

2008 ◽

Vol 23 (10) ◽

pp. 1877-1882 ◽

Cited By ~ 19

Author(s):

Shuichiro Fujinaga ◽

Yoshiyuki Ohtomo ◽

Satoshi Hara ◽

Daisuke Umino ◽

Tomonosuke Someya ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Maintenance Therapy ◽

Low Dose ◽

Intravenous Cyclophosphamide ◽

Severe 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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