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Outcomes following mycophenolate mofetil versus cyclophosphamide induction treatment for proliferative juvenile-onset lupus nephritis

Author

Smith E1,2, Al-Abadi E3, Armon K4, Bailey K5, Ciurtin C6, Davidson J7, Gardner-Medwin J8, Haslam K9, Hawley D10, Leahy A11, Leone V12, McErlane F13, Mewar D14, Modgil G15, Moots R16, Pilkington C17, Ramanan A18, Rangaraj S19, Riley P20, Sridhar A21, Wilkinson N22, Beresford MW1,2, Hedrich CM1,2. Lupus. 2019 Mar 14:961203319836712. doi: 10.1177/0961203319836712. [Epub ahead of print]

Author Information

1 Department of Women and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.

2 Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust, Liverpool, UK.

3 Department of Rheumatology, Birmingham Children's Hospital, Birmingham, UK.

4 Department of Paediatric Rheumatology, Cambridge University Hospitals, Cambridge, UK.

5 Department of Paediatric Rheumatology, Oxford University Hospitals, Oxford, UK.

6 Department of Rheumatology, University College London Hospitals NHS Foundation Trust, London, UK.

7 Department of Paediatric Rheumatology, Royal Hospital for Sick Children, Edinburgh, UK.

8 Department of Paediatric Rheumatology, NHS Greater Glasgow and Clyde (Yorkhill Division), Glasgow, UK.

9 Department of Paediatrics, Bradford Royal Infirmary, Bradford, UK.

10 Department of Paediatric Rheumatology, Sheffield Children's Hospital, Sheffield, UK.

11 Department of Paediatric Rheumatology, Southampton General Hospital, Southampton, UK.

12 Department of Paediatric Rheumatology, Leeds General Infirmary, Leeds, UK.

13 Department of Paediatric Rheumatology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.

14 Department of Rheumatology, Royal Liverpool University Hospital, Liverpool, UK.

15 Department of Paediatrics, Musgrove Park Hospital, Taunton, UK.

16 Department of Rheumatology, University Hospital Aintree, Liverpool, UK.

17 Department of Paediatric Rheumatology, Great Ormond Street Hospital, London, UK.

18 Department of Paediatric Rheumatology, Bristol Royal Hospital for Children, Bristol, UK.

19 Department of Paediatric Rheumatology, Nottingham University Hospitals, Nottingham, UK.

20 Department of Paediatric Rheumatology, Royal Manchester Children's Hospital, Manchester, UK.

21 Department of Paediatrics, Leicester Royal Infirmary, Leicester, UK.

22 Guy's and St Thomas's NHS Foundation Trust, Evelina Children's Hospital, London, UK.

Abstract

BACKGROUND: 

Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC).

METHODS: 

UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann-Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis.

RESULTS: 

Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4-8 and 10-14 months post-renal biopsy and last follow-up, in terms of renal British Isles LupusAssessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141-390) days after MMF treatment, and 151 (117-305) days following IVCYC ( p = 0.17). Time to renal flare was 451 (157-1266) days for MMF, and 343 (198-635) days for IVCYC ( p = 0.47).

CONCLUSION: 

This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.