WITHDRAWN: Long-term data on sirolimus treatment in patients with lupus nephritis

Desmond Y.H Yap,Tak Mao Chan,Colin Tang,Maggie K.M Ma,Maggie M.Y Mok,Gary C.W Chan,Lorraine P.Y Kwan

doi:10.18632/oncotarget.24200

Abstract

// Desmond Y.H. YAP 1 , Colin Tang 1 , Gary C.W. Chan 1 , Lorraine P.Y. Kwan 1 , Maggie K.M. Ma 1 , Maggie M.Y. Mok 1 and Tak Mao Chan 1 1 Division of Nephrology, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong Correspondence to: Tak Mao Chan, email: dtmchan@hku.hk Keywords: sirolimus; mTOR; malignancy; lupus nephritis; long-term Received: October 11, 2017      Accepted: December 05, 2017      Published: January 12, 2018 ABSTRACT Our pilot short-term data suggested efficacy of sirolimus treatment in lupus nephritis (LN) patients, but its long-term data remains limited. We retrospectively reviewed 16 Class III/IV/V LN patients who have received prednisolone and sirolimus either as initial or maintenance treatment. Sixteen patients received sirolimus treatment (9 due to intolerance to standard immunosuppressants and 7 due to a history of malignancy) for 45.3 ± 36.5 months. In five patients sirolimus and prednisolone was given as induction for active nephritis, and they showed improvements in proteinuria (2.8 ± 1.9 g/day at baseline, 0.1 ± 0.1 g/day after 36 months, p = 0.011), anti-dsDNA (107.7 ± 91.9 IU/mL and 37.0 ± 55.4 IU/mL respectively, p = 0.178) and C3 (54.8 ± 26.1 mg/dL and 86.3 ± 18.6 mg/dL respectively, p = 0.081). Eleven patients received sirolimus and low-dose prednisolone as long-term maintenance, and they showed continued improvement in C3 (90.4 ± 18.1 mg/dL and 117.7±25.1 mg/dL at commencement and after 36 months respectively, p = 0.025) and stable renal function (eGFR 58.6 ± 25.8 ml/min and 63.0 ± 29.6 mL/min respectively, p = 0.239) and proteinuria (0.8 ± 0.7 g/day and 0.7 ± 0.7 g/day respectively, p = 0.252). Renal flare occurred in one patient and another patient with Stage 4 chronic kidney disease when sirolimus was started developed endstage renal failure after 27 months. Sirolimus was discontinued in five patients, in four cases related to drug side-effects. Deterioration of dyslipidaemia occurred in four patients, but was adequately controlled with statin therapy. The preliminary evidence suggests that sirolimus may serve as an alternative treatment for LN who do not tolerate standard treatment or had history of malignancy, and with acceptable long-term safety profile.

Highlights

Lupus nephritis (LN) is a serious organ involvement in patients with systemic lupus erythematosus (SLE), and is associated with excessive patient mortality [1, 2]
We retrospectively reviewed 16 Class III/IV/V lupus nephritis (LN) patients who have received prednisolone and sirolimus either as initial or maintenance treatment
The preliminary evidence suggests that sirolimus may serve as an alternative treatment for LN who do not tolerate standard treatment or had history of malignancy, and with acceptable long-term safety profile

Summary

Introduction

Lupus nephritis (LN) is a serious organ involvement in patients with systemic lupus erythematosus (SLE), and is associated with excessive patient mortality [1, 2]. The current standardof-care induction treatments for active severe LN are corticosteroids combined with either cyclophosphamide (CYC) or mycophenolate mofetil (MMF), followed by low-dose corticosteroids plus either MMF or azathioprine (AZA) maintenance to prevent relapse [4,5,6,7,8] While these immunosuppressive regimens have established short- and long-term efficacy for the treatment of LN, each agent is associated with its potential toxicities and there is always a keen demand for novel therapeutic agents to www.impactjournals.com/oncotarget facilitate tailoring treatment according to the distinct needs of individual patients [9,10,11,12]

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