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

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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Rituximab and mycophenolate mofetil for relapsing proliferative lupus nephritis: a long-term prospective study

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfp002 ◽

2009 ◽

Vol 24 (7) ◽

pp. 2157-2160 ◽

Cited By ~ 45

Author(s):

John N. Boletis ◽

Smaragde Marinaki ◽

Chryssanthe Skalioti ◽

Sofia S. Lionaki ◽

Aliki Iniotaki ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Prospective Study ◽

Proliferative Lupus Nephritis

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Efficacy of long-term maintenance therapy with mycophenolate mofetil in lupus nephritis

SpringerPlus ◽

10.1186/2193-1801-3-638 ◽

2014 ◽

Vol 3 (1) ◽

Cited By ~ 2

Author(s):

Zahra Rezaieyazdi ◽

Tahmine Tavakoli ◽

Mohammad Khajehdaluee ◽

Shahram Honarmand

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Maintenance Therapy ◽

Term Maintenance

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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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Long-Term Study of Mycophenolate Mofetil as Continuous Induction and Maintenance Treatment for Diffuse Proliferative Lupus Nephritis

Journal of the American Society of Nephrology ◽

10.1681/asn.2004080686 ◽

2005 ◽

Vol 16 (4) ◽

pp. 1076-1084 ◽

Cited By ~ 343

Author(s):

Tak-Mao Chan ◽

Kai-Chung Tse ◽

Colin Siu-On Tang ◽

Mo-Yin Mok ◽

Fu-Keung Li

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Maintenance Treatment ◽

Term Study ◽

Long Term Study ◽

Proliferative Lupus Nephritis ◽

Continuous Induction

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A Prospective Study on Long-Term Clinical Outcomes of Patients with Lupus Nephritis treated with an Intensified B-Cell Depletion Protocol without Maintenance Therapy

Kidney International Reports ◽

10.1016/j.ekir.2021.01.027 ◽

2021 ◽

Author(s):

Dario Roccatello ◽

Savino Sciascia ◽

Carla Naretto ◽

Mirella Alpa ◽

Roberta Fenoglio ◽

...

Keyword(s):

Lupus Nephritis ◽

Maintenance Therapy ◽

Prospective Study ◽

B Cell ◽

Clinical Outcomes ◽

Cell Depletion ◽

B Cell Depletion ◽

A Prospective Study

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Long-term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil

Lupus ◽

10.1177/0961203320926256 ◽

2020 ◽

Vol 29 (8) ◽

pp. 845-853

Author(s):

Narayan Prasad ◽

Jithu Kurian ◽

Vikas Agarwal ◽

Dharmendra Bhadauria ◽

Manas Behera ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Maintenance Therapy ◽

Patient Survival ◽

Survival Rates ◽

Class Iii ◽

Renal Survival ◽

Long Term Outcomes ◽

Class Iv

Introduction Lupus nephritis (LN) has a considerable impact on the morbidity and mortality of systemic lupus erythematosus (SLE) patients. Long-term comparative outcome data from the Indian subcontinent on treatment regimens with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) are sparse. We assessed renal and patient survival for these patients in terms of the types of induction – CYP or MMF – and the two maintenance therapies – MMF or azathioprine (AZA). Methods We retrospectively analysed outcomes of 100 LN patients, 67 treated with CYP (26 class III, 25 class IV, 6 class III + V and 10 class IV + V; 40 Euro lupus regimen and 27 National Institutes of Health regimen) and 33 treated with a MMF-based regimen with steroids between July 2008 and June 2018. Data regarding demographic, clinical and histopathological features and the treatment given to all patients were extracted. Outcomes between the two regimens CYP and MMF were compared in terms of remission, dialysis and patient survival. Results The clinical characteristics were similar in both groups, except that the activity index was higher in CYP patients (6.13 ± 4.48 vs. 4.61 ± 2.80). However, the chronicity index was similar. The overall remission rate was 70% at the end of induction. The rates of complete remission, partial remission and non-responders in the CYP group were 46.2%, 23.9% and 29.9%, respectively. However, in the MMF group, the corresponding rates were 57.6%, 12.1% and 30.3%, respectively. The 1-, 2-, 3-, 4-, 5- and 10-year patient survival rates in the CYP group were 89.5%, 86.2%, 86.2%, 83.8%, 83.8% and 83.8%, respectively. In the MMF induction group, the corresponding rates were 93.9%, 93.9%, 89%, 89%, 89% and 89%, respectively. At the end of the study, rates of end-stage renal disease in the MMF group and CYP group were 7.5% and 12.1%, respectively. The death-censored and non-censored renal survival rates were also similar in the long term. With regard to maintenance therapy, 3/56 (5.3%) in the MMF group and 7/34 (20.5%) in the AZA group experienced doubling of serum creatinine ( p = 0.03). Conclusions Long-term outcomes in terms of patient and renal survival of LN patients treated with CYP and MMF induction are similar. Doubling of serum creatinine occurred more with AZA-based maintenance therapy than with MMF-based maintenance therapy. Most deaths occurred during induction, and sepsis was the most common cause of death.

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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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A randomised controlled trial evaluating the effects of long-term low-dose corticosteroid therapy compared to placebo on flare rates during maintenance therapy for proliferative lupus nephritis: a pilot study

http://isrctn.org/> ◽

10.1186/isrctn31327267 ◽

2012 ◽

Author(s):

Braden Manns

Keyword(s):

Pilot Study ◽

Randomised Controlled Trial ◽

Lupus Nephritis ◽

Maintenance Therapy ◽

Low Dose ◽

Controlled Trial ◽

Proliferative Lupus Nephritis ◽

Dose Corticosteroid ◽

Randomised Controlled

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

Journal of International Medical Research ◽

10.1177/0300060518796751 ◽

2018 ◽

Vol 47 (1) ◽

pp. 105-113 ◽

Cited By ~ 2

Author(s):

Youying Mao ◽

Lei Yin ◽

Hua Huang ◽

Zhengyu Zhou ◽

Tongxin Chen ◽

...

Keyword(s):

Mycophenolate Mofetil ◽

Lupus Nephritis ◽

Adverse Effects ◽

Adverse Events ◽

Maintenance Therapy ◽

Clinical Response ◽

Low Dose ◽

Good Choice ◽

Proliferative Lupus Nephritis ◽

Remission Rates

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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