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Original article
peer-reviewed

Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy



Abstract

Background and objective

The rate of end-stage renal disease from lupus nephritis has not declined, in spite of recent advances in therapeutics, such as mycophenolate mofetil (MMF). To provide insight into rates of the clinical outcomes in current practice after biopsy-proven lupus nephritis, we used a prospective cohort of the patients with newly diagnosed lupus nephritis, treated with MMF and observed their outcomes.

Method

Twenty systemic lupus erythematosus (SLE) patients who began mycophenolate mofetil shortly after a biopsy-confirmed diagnosis of lupus nephritis were included in the analysis. There were five patients with class III, nine with class IV, four with class III-V, one with class IV-V and two with class V lupus nephritis. The initial dose of mycophenolate mofetil was 1000 mg twice daily. If no improvement was observed, the dose was increased to 1500 mg twice daily after one month. We estimated the survival function for the time until the urine protein/creatinine reached 0.50 grams or less, after starting MMF by using an approach that accommodated interval-censored data. We also evaluated the treatment response using five different sets of criteria for the response that have previously been used in the clinical trials. These included the Bristol Myers-Squibb (BMS), the American College of Rheumatology (ACR), the lupus nephritis assessment with rituximab (LUNAR ), the Aspreva Lupus Management Study (ALMS), and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS).

Result

We estimated that 52% of the SLE patients reached 0.50 grams of proteinuria within 51 days of starting mycophenolate mofetil (95% confidence interval 29%-74%) and 77% reached 0.50 grams or less within 260 days (95% confidence interval 57%-97%). The probability of response at 90 and 180 days was 5% and 33% (the Bristol Myers-Squibb), 26% and 57% (the American College of Rheumatology), and 11% and 28% (the lupus nephritis assessment with rituximab, the Aspreva Lupus Management Study and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study).

Conclusion

The complete renal response ranged from 28% to 57% at six months in the routine clinical practice, mirroring the results in randomized clinical trials. Regardless of the response measures, the complete renal response was slow and, by most indices, reached in only a minority of the patients by the end of six months of the induction therapy. This indicates the urgent need for the faster and more effective lupus nephritis treatments.



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Original article
peer-reviewed

Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy


Author Information

Homa Timlin Corresponding Author

Medicine, The Johns Hopkins University School of Medicine

Laurence Magder

Epidemiology and Public Health, University of Maryland School of Medicine

Michelle Petri

Rheumatology, The Johns Hopkins University School of Medicine


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. John Hopkins IRB issued approval NA-00039294. The Hopkins Lupus Cohort was approved annually by the Johns Hopkins University School of Medicine. The written consent was obtained from all the patients. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: I have communicated with all of my co-authors and obtained their full disclosure.
The authors declare that they have no competing interests:
Homa Timlin, MSc. MRCP: None
Laurence S Magder Ph.D. M.P.H: None

The study was supported by NIH AR 043727 and 069572
Recipient of both grants: Michelle Petri M.D. M.P.H. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.


Original article
peer-reviewed

Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy


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Original article
peer-reviewed

Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy

Homa Timlin">Homa Timlin , Laurence Magder">Laurence Magder, Michelle Petri">Michelle Petri

  • Author Information
    Homa Timlin Corresponding Author

    Medicine, The Johns Hopkins University School of Medicine

    Laurence Magder

    Epidemiology and Public Health, University of Maryland School of Medicine

    Michelle Petri

    Rheumatology, The Johns Hopkins University School of Medicine


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: Consent was obtained by all participants in this study. John Hopkins IRB issued approval NA-00039294. The Hopkins Lupus Cohort was approved annually by the Johns Hopkins University School of Medicine. The written consent was obtained from all the patients. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: I have communicated with all of my co-authors and obtained their full disclosure.
    The authors declare that they have no competing interests:
    Homa Timlin, MSc. MRCP: None
    Laurence S Magder Ph.D. M.P.H: None

    The study was supported by NIH AR 043727 and 069572
    Recipient of both grants: Michelle Petri M.D. M.P.H. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements


    Article Information

    Published: December 04, 2017

    DOI

    10.7759/cureus.1907

    Cite this article as:

    Timlin H, Magder L, Petri M (December 04, 2017) Clinical Outcomes Observed among Biopsy Proven Lupus Nephritis Patients Treated with Mycophenolate Mofetil as First-line Therapy. Cureus 9(12): e1907. doi:10.7759/cureus.1907

    Publication history

    Received by Cureus: November 10, 2017
    Peer review began: November 15, 2017
    Peer review concluded: November 30, 2017
    Published: December 04, 2017

    Copyright

    © Copyright 2017
    Timlin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background and objective

The rate of end-stage renal disease from lupus nephritis has not declined, in spite of recent advances in therapeutics, such as mycophenolate mofetil (MMF). To provide insight into rates of the clinical outcomes in current practice after biopsy-proven lupus nephritis, we used a prospective cohort of the patients with newly diagnosed lupus nephritis, treated with MMF and observed their outcomes.

Method

Twenty systemic lupus erythematosus (SLE) patients who began mycophenolate mofetil shortly after a biopsy-confirmed diagnosis of lupus nephritis were included in the analysis. There were five patients with class III, nine with class IV, four with class III-V, one with class IV-V and two with class V lupus nephritis. The initial dose of mycophenolate mofetil was 1000 mg twice daily. If no improvement was observed, the dose was increased to 1500 mg twice daily after one month. We estimated the survival function for the time until the urine protein/creatinine reached 0.50 grams or less, after starting MMF by using an approach that accommodated interval-censored data. We also evaluated the treatment response using five different sets of criteria for the response that have previously been used in the clinical trials. These included the Bristol Myers-Squibb (BMS), the American College of Rheumatology (ACR), the lupus nephritis assessment with rituximab (LUNAR ), the Aspreva Lupus Management Study (ALMS), and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study (ACCESS).

Result

We estimated that 52% of the SLE patients reached 0.50 grams of proteinuria within 51 days of starting mycophenolate mofetil (95% confidence interval 29%-74%) and 77% reached 0.50 grams or less within 260 days (95% confidence interval 57%-97%). The probability of response at 90 and 180 days was 5% and 33% (the Bristol Myers-Squibb), 26% and 57% (the American College of Rheumatology), and 11% and 28% (the lupus nephritis assessment with rituximab, the Aspreva Lupus Management Study and the Abatacept and Cyclophosphamide Combination Efficacy and Safety Study).

Conclusion

The complete renal response ranged from 28% to 57% at six months in the routine clinical practice, mirroring the results in randomized clinical trials. Regardless of the response measures, the complete renal response was slow and, by most indices, reached in only a minority of the patients by the end of six months of the induction therapy. This indicates the urgent need for the faster and more effective lupus nephritis treatments.



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Create a free account to continue reading this article.

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Homa Timlin

Medicine, The Johns Hopkins University School of Medicine

For correspondence:
htimlin1@jhmi.edu

Laurence Magder

Epidemiology and Public Health, University of Maryland School of Medicine

Michelle Petri

Rheumatology, The Johns Hopkins University School of Medicine

Homa Timlin

Medicine, The Johns Hopkins University School of Medicine

For correspondence:
htimlin1@jhmi.edu

Laurence Magder

Epidemiology and Public Health, University of Maryland School of Medicine

Michelle Petri

Rheumatology, The Johns Hopkins University School of Medicine