Comparing the efficacy of low-dose vs high-dose cyclophosphamide regimen as induction therapy in the treatment of proliferative lupus nephritis: a single center study

  • Sonal Mehra
  • Jignesh B. Usdadiya
  • Vikramraj K. Jain
  • Durga Prasanna Misra
  • Vir Singh Negi
Clinical Trials
  • 8 Downloads

Abstract

Cyclophosphamide (CYC) has been the backbone immunosuppressive drug to achieve sustained remission in lupus nephritis (LN). The aim was to evaluate the efficacy and compare adverse effects of low and high dose intravenous CYC therapy in Indian patients with proliferative lupus nephritis. An open-label, parallel group, randomized controlled trial involving 75 patients with class III/IV LN was conducted after obtaining informed consent. The low dose group (n = 38) received 6 × 500 mg CYC fortnightly and high dose group (n = 37) received 6 × 750 mg/m2 CYC four-weekly followed by azathioprine. The primary outcome was complete/partial/no response at 52 weeks. The secondary outcomes were renal and non-renal flares and adverse events. Intention-to-treat analyses were performed. At 52 weeks, 27 (73%) in high dose group achieved complete/partial response (CR/PR) vs 19 (50%) in low dose (p = 0.04). CR was higher in the high dose vs low dose [24 (65%) vs 17 (44%)], although not statistically significant. Non-responders (NR) in the high dose group were also significantly lower 10 (27%) vs low dose 19 (50%) (p = 0.04). The change in the SLEDAI (Median, IQR) was also higher in the high dose 16 (7–20) in contrast to the low dose 10 (5.5–14) (p = 0.04). There was significant alopecia and CYC-induced leucopenia in high dose group. Renal relapses were significantly higher in the low dose group vs high dose [9 (24%) vs 1(3%), (p = 0.01)]. At 52 weeks, high dose CYC was more effective in inducing remission with decreased renal relapses in our population.

Trial Registration: The study was registered at http://www.clintrials.gov. NCT02645565.

Keywords

Systemic lupus erythematosus Lupus nephritis Cyclophosphamide Adverse effect Efficacy 

Abbreviations

ACR

American College of Rheumatology

ALMS

The Aspreva Lupus Management Study

CBC

Complete blood count

CYC

Cyclophosphamide

CR

Complete response

C3, C4

Complement component 3 and 4

dsDNA

Double-stranded deoxyribonucleic acid

eGFR

Estimated glomerular filtration rate

ELISA

Enzyme-linked immunosorbent assay

ELNT

Euro Lupus Nephritis Trial

HPF

High power field

IV

Intravenous

ISN/RPS

International Society of Nephrology/Renal Pathology Society

ITT

Intention to treat

IQR

Interquartile range

LN

Lupus nephritis

LDL-C

Low-density lipoprotein cholesterol

MDRD

Modification of Diet in Renal Disease

MMF

Mycophenolate mofetil

NR

No response

NIH

National Institutes of Health

PR

Partial response

RBC

Red Blood cell

SD

Standard deviation

SLEDAI

Systemic Lupus Erythematosus Disease Activity Index

WBC

White blood cell

Notes

Acknowledgements

We thank the Indian rheumatology association for providing us funding for this project on lupus nephritis.

Compliance with ethical standards

Conflict of interest

Sonal Mehra declares that she has no conflict of interest. Jignesh Usdadiya declares that he has no conflict of interest. Vikramraj Jain declares that he has no conflict of interest. Durga Prasanna Misra declares that he has no conflict of interest. Vir Singh Negi declares that he has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Jawaharlal Institute of post graduate medical education and research committee Number : JIP/IEC/SC/2013/5/435 dated 4.3.2014 and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

296_2018_3995_MOESM1_ESM.docx (184 kb)
Supplementary material 1 (DOCX 184 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Clinical ImmunologyJawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)PuducherryIndia
  2. 2.Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia

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