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

Lupus ◽  
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.

P0451TEN-YEAR OUTCOME DIFFERENCES IN LUPUS NEPHRITIS PATIENTS TREATED WITH CYCLOPHOSHAMIDE AND MYCOPHENOLATE- BASED TREATMENT REGIMEN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Narayan Prasad ◽  
Jithu Kurian ◽  
Vikas Agarwal ◽  
Dharmendra Bhadauria ◽  
Amit Gupta
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Cause Of Death ◽  
Patient Survival ◽  
Class Iii ◽  
Renal Survival ◽  
Common Cause ◽  
Class Iv

Abstract Background and Aims Lupus nephritis (LN) poses a considerable impact on the morbidity and mortality of SLE patients. Long term comparative outcome data with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) based regimen from the Indian subcontinent is sparse. We assessed the renal and patient survival of these patients for the types of induction CYP or MMF and the two maintenance therapies – MMF or Azathioprine. We determined the predictors of death and dialysis dependency in the study population. Method In this retrospective study, we analysed outcomes of 100 LN patients, total 67 (26 class III, 25 class IV, 6 class III+V, and 10 class IV+V)) treated with CYP (euro lupus-40 and NIH- Dharmendra Bhadauria 27), and 33 with MMF based regimen with the steroid between July 2008 to June 2018. The class distribution of the patients in the two groups was similar. The data were archived regarding demography, clinical, histopathological features, and the treatment given of all 100 biopsy-proven LN patients. Outcomes between two regimens CYP and MMF in terms of remission, dialysis dependency, and patient survival were compared. The renal survival and patient survival at the end of follow-up between two groups were also analysed. Results The clinical characteristics were similar in both groups, except the activity index was high in CYP patients (6.13 ±4.48 Vs. 4.61 ± 2.80); however, the chronicity index was similar. The overall remission was 70% at the end of induction. The CR, PR, and NR in the CYP group was 46.2%, 23.9 %, 29.9% respectively; however, in the MMF group was 57.6%, 12.1%, and 30.3%, respectively. More patients died in CYP (14.9%) than those in MMF (9.1 %) patients. The 1-, 2-, 3-, 4-, 5- and 10-years patient survival in the CYP induction was 89.5%, 86.2%, 86.2%,83.8%, 83.8% and 83.8% however in MMF was 93.9%, 93.9%, 89%, 89%, 89% and 89% respectively. The most common cause of death was sepsis 9/13(69.2%), followed by uremia. The high serum creatinine, low Hb, male, thrombocytopenia, microscopic haematuria, leukocyturia, nephrotic proteinuria, lack of remission in 12 months, dialysis, doubling of creatinine on follow-up were significant predictors of mortality. The 1-, 2- 3-, 4-, 5- and 10- years renal survival (event death-censored, but dialysis dependency) in CP group was 98.5%, 96.7%, 94.7%, 92.4%, 92.4% and 84 % respectively however in the MMF was 96.8 %, 96.8%, 91.9%, 91.9%, 91.9%, and 78.8% respectively. (Figure 1)At the end of the study, dialysis dependency in the MMF group and CYP group was 7.5% and 12.1 %, respectively (NS). In the maintenance therapy, 3/56(5.3%) had to double of creatinine in MMF, and 7/34 (20.5%) in the AZA group (p=0.03). Conclusion Long term outcomes in terms of patient and renal survival of LN patients treated with CP and MMF based induction is similar. Serum creatinine doubling was more with MMF than AZA based maintenance. The majority of death occurred during induction, and sepsis was the most common cause of death.

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

2015 ◽  
Vol 75 (3) ◽  
pp. 526-531 ◽  
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.

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

SpringerPlus ◽  
2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Zahra Rezaieyazdi ◽  
Tahmine Tavakoli ◽  
Mohammad Khajehdaluee ◽  
Shahram Honarmand
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Maintenance Therapy ◽  
Term Maintenance

Long-term outcomes--mycophenolate mofetil treatment for lupus nephritis with addition of tacrolimus for resistant cases

2010 ◽  
Vol 25 (12) ◽  
pp. 3939-3948 ◽  
Author(s):  
J. Cortes-Hernandez ◽  
M. T. Torres-Salido ◽  
A. S. Medrano ◽  
M. V. Tarres ◽  
J. Ordi-Ros
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Long Term Outcomes

Antiphospholipid antibodies in patients with lupus nephritis: clinical correlations and associations with long-term outcomes

Lupus ◽  
2019 ◽  
Vol 28 (12) ◽  
pp. 1460-1467 ◽  
Author(s):  
D Y H Yap ◽  
K M Thong ◽  
S Yung ◽  
C Tang ◽  
B M Y Ma ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Antiphospholipid Antibodies ◽  
Bleeding Complications ◽  
Rapid Decline ◽  
Renal Survival ◽  
Long Term Outcomes ◽  
Glycoprotein I ◽  
Clinical Correlations

Whether the presence or absence of antiphospholipid antibodies (aPL) in patients with lupus nephritis (LN) is associated with differences in clinical outcomes remains unclear. We reviewed LN patients at a single centre during 2000–2017, and compared the clinical features and long-term outcomes between patients who were seropositive or seronegative for aPL. aPL was detected in 53/149 (35.6%) patients with biopsy-proven LN, and anticardiolipin IgM, anticardiolipin IgG, anti-β2 glycoprotein I and lupus anticoagulant was detected in 18.8%, 18.1%, 10.7% and 8.1%, respectively. Follow-up was 155.8 ± 61.0 months, and was similar between aPL-seropositive and -seronegative patients. aPL seropositivity persisted in 94.3% of patients during remission. aPL-seropositive patients showed inferior patient survival (91% and 85% at 10 and 15 years, respectively, compared to 99% and 95% in aPL-seronegative patients; p = 0.043). Nine (6.0%) patients died during follow-up, including six aPL-seropositive (four thrombotic events and two bleeding complications related to anticoagulation) and three aPL-seronegative patients. aPL seropositivity was associated with more rapid decline in estimated glomerular filtration rate (–1.44 mL/min/year compared to –0.38 mL/min/year in aPL-seronegative patients; p = 0.027) and inferior long-term renal survival (82% and 74% at 10 and 15 years, respectively, compared to 91% and 87% in aPL-seronegative patients; p = 0.034). aPL-seropositive patients also had a higher incidence of thrombotic events and miscarriage (32.1% and 13.2%, respectively, compared to 16.7% and 2.1% in the aPL-seronegative group; p = 0.030 and 0.006). We concluded that aPL seropositivity was associated with inferior long-term patient and renal survival and more frequent thrombotic events and miscarriage in LN patients.

Lupus Nephritis: Induction Therapy

Lupus ◽  
2005 ◽  
Vol 14 (3_suppl) ◽  
pp. 27-32 ◽  
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.

Comparing the Effect of rATG Dosing on Long-Term Outcomes in Young (40-59) and Elderly (≥60) Kidney Transplant Recipients

2021 ◽  
Author(s):  
Iman Bajjoka ◽  
Salvatore Serra ◽  
Jade Mourad ◽  
Catherine Crombez ◽  
Mohamed Safwan ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Graft Survival ◽  
Patient Survival ◽  
Statistical Tests ◽  
Survival Rates ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Long Term Outcomes ◽  
Long Term Outcome

Abstract BackgroundAs the number of elderly kidney transplant recipients increases, long-term outcome differences between this population and younger kidney transplant recipients are not well documented. The purpose of the study is to evaluate the effect of rATG dosing on long-term outcomes between elderly and young kidney transplant recipients.MethodsA single-center retrospective analysis of medical records of 688 first-time kidney transplant recipients (KTR) from 2003 to 2014 on a regimen of mycophenolate mofetil, tacrolimus, and steroids was performed. During the 11-year period there were no immunosuppresion protocol changes. Baseline characteristics, first biopsy-proven acute rejection (BPAR), estimated glomerular filtration rates (eGFR), graft survival, and patient survival at discharge and annually up to 5 years post-transplant were analyzed. Various statistical tests including Chi-square test, two-sample t-test, and Mann-Whitney U test were used to compare data obtained from this study.ResultsThe study population was divided into two cohorts: elderly (E-KTR) (≥60 years; n=277) and younger (Y-KTR) (40-59 years; n=411). E-KTR received more expanded criteria donor kidneys (p<0.001) and older donor kidneys (p<0.001). Y-KTR experienced more BPAR in incidence (p<0.001) than E-KTR, however, the severity of BPAR was similar. A difference in eGFR was observed at discharge, where Y-KTR had better eGFR rates than E-KTR (p<0.05). At 5-years, a trend was observed indicating that E-KTR have better eGFR rates than Y-KTR. Despite similar long-term graft survival, patient survival was significantly lower among the elderly patients (p<0.01). An indication for higher mortality rates in E-KTR is due to rATG dosing for which we found that mortality increased with patients who received high rATG doses in comparison to low doses (p<0.05).ConclusionE-KTR had lower patient survival rates yet similar graft survival rates when compared to Y-KTR. Lower survival rates in E-KTR was associated with higher rATG dosing. Larger validation studies need to be performed to assess the benefit of using less harmful immunosuppressants to improve long-term outcomes for E-KTR.

Remission and long-term outcomes of proliferative lupus nephritis: retrospective study of 96 patients from Saudi Arabia

Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1082-1090 ◽  
Author(s):  
A H Almalki ◽  
F A Alrowaie ◽  
H M Alhozali ◽  
N K Almalki ◽  
A I Alsubei ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Lupus Erythematosus ◽  
Severe Disease ◽  
Induction Agent ◽  
Renal Survival ◽  
Long Term Outcomes ◽  
Proliferative Lupus Nephritis ◽  
Cumulative Rate

Background Few data are available about the rate of short-term remission and its impact on the long-term outcomes of proliferative lupus nephritis in the Middle East. Methods An observational study was carried out involving 96 adult patients with biopsy-proven focal or diffuse proliferative lupus nephritis (PLN) from four different hospitals. Data on induction, remission and long-term outcomes were collected and analyzed. Results Among the 96 patients with biopsy-proven PLN (median age 27 (IQR: 21,34) years, 85% women and median duration of systemic lupus erythematosus (SLE) prior to diagnosis 27 (IQR: 11, 55) months), 67% developed remission at 6 months (proportion 0.67; 95% CI 0.57, 0.76). Mycophenolate mofetil (MMF) was used in 45/96 (47%), CYC in 41/95 (43%) and other agents in 10/96 (10%). The choice of MMF as induction agent has increased in recent years. Among baseline characteristics, only histologic activity was found to have a significant association with remission, with active lesions more likely to remit than active/chronic and chronic lesions (AOR 6.5, 95% CI 1.44–29.39, p = 0.015). Based on Kaplan–Meier analysis, the 5-year renal survival rate without doubling serum creatinine was 73.8%. Compared to patients with complete remission, lower long-term renal survival rates were observed in patients with no remission (89.7 versus 43%, p = 0.001) and partial remission (89.7 versus 77.6%, p = 0.256). The cumulative rate of doubling serum creatinine, dialysis, relapse and death was 23%, 11%, 10% and 5%, respectively, at 48-month median follow up. Conclusion Approximately two-thirds of patients with PLN develop remission in response to standard induction therapy. Remission was negatively associated with the presence of chronic changes in renal biopsy. Overall, MMF is the most commonly used agent to induce remission; however, with more severe disease CYC, is used more frequently. PLN is associated with significant long-term renal outcomes including a 26% cumulative rate of doubling of serum creatinine at 5 years. Initial remission predicts this long-term renal survival.

scholarly journals Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis

Leukemia ◽  
2021 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Timothy P. Hughes ◽  
Richard A. Larson ◽  
Dong-Wook Kim ◽  
Surapol Issaragrisil ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Chronic Phase ◽  
Individual Treatment ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Long Term Outcomes ◽  
Treatment Free Remission

AbstractIn the ENESTnd study, with ≥10 years follow-up in patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase, nilotinib demonstrated higher cumulative molecular response rates, lower rates of disease progression and CML-related death, and increased eligibility for treatment-free remission (TFR). Cumulative 10-year rates of MMR and MR4.5 were higher with nilotinib (300 mg twice daily [BID], 77.7% and 61.0%, respectively; 400 mg BID, 79.7% and 61.2%, respectively) than with imatinib (400 mg once daily [QD], 62.5% and 39.2%, respectively). Cumulative rates of TFR eligibility at 10 years were higher with nilotinib (300 mg BID, 48.6%; 400 mg BID, 47.3%) vs imatinib (29.7%). Estimated 10-year overall survival rates in nilotinib and imatinib arms were 87.6%, 90.3%, and 88.3%, respectively. Overall frequency of adverse events was similar with nilotinib and imatinib. By 10 years, higher cumulative rates of cardiovascular events were reported with nilotinib (300 mg BID, 16.5%; 400 mg BID, 23.5%) vs imatinib (3.6%), including in Framingham low-risk patients. Overall efficacy and safety results support the use of nilotinib 300 mg BID as frontline therapy for optimal long-term outcomes, especially in patients aiming for TFR. The benefit-risk profile in context of individual treatment goals should be carefully assessed.

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