Outcomes of multitarget therapy using mycophenolate mofetil and tacrolimus for refractory or relapsing lupus nephritis

Abstract

Objectives

Outcomes of systemic lupus erythematosus (SLE) have significantly improved over the years. However, when there is major organ involvement, the outcomes can still be unfavorable. Outcomes of multitarget therapy using mycophenolate mofetil (MMF) and tacrolimus in patients with SLE who were refractory to standard therapy were assessed.

Methods

We retrospectively reviewed the Hanyang BAE lupus cohort to identify patients with biopsy-confirmed lupus nephritis (classes III, IV, or V) who failed to either achieve complete response with standard induction therapy or those who had a lupus flare after achieving a complete response with conventional induction therapy and subsequently were switched to multitarget combination therapy with MMF and tacrolimus. Outcomes, including renal response, proteinuria, glomerular filtration rate, serum albumin, anti-dsDNA antibody level, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and complements, were assessed at six and 12 months.

Results

Twenty-nine patients, including 12 who failed to achieve a complete response at 12 months after initial conventional induction therapy and 17 with lupus flare after achieving a complete response at 12 months and treated with multitarget therapy, were included in the analysis. At six months, 53.9% of the patients showed a response, with 15.4% of patients showing a complete response and 38.5% of patients showing a partial response. At 12 months, 55.5% of patients exhibited a response (with complete and partial response in 25.9% and 29.6%, respectively). The dosage of steroids was significantly decreased at six months compared with baseline and was maintained at 12 months. Proteinuria, anti-double-stranded DNA antibody positivity, as well as C3 and C4 levels improved after treatment and persisted until 12 months, but were not significant. SLEDAI also improved. Outcomes were significantly better in patients who had a complete response but later had a flare, resulting in the use of multitarget therapy and achieving a subsequent complete response.

Conclusions

Multitarget therapy with MMF and tacrolimus can be a reasonable option in refractory lupus nephritis patients who failed to show adequate response to conventional induction therapy or who had flares during maintenance therapy. This treatment can help patients achieve a renal response and reduce the use of steroids.

Keywords

Systemic lupus erythematosus nephritis mycophenolate mofetil tactolimus multitarget therapy

Get full access to this article

View all access options for this article.

References

Kaul

Gordon

Crow

et al.

Systemic lupus erythematosus. Nat Rev Dis Prim 2016; 2: 16039–16039.

Mok

. Towards new avenues in the management of lupus glomerulonephritis. Nat Rev Rheumatol 2016; 12: 221–234.

Bao

Liu

Xie

Zhang

. Successful treatment of class V + IV lupus nephritis with multitarget therapy. J Am Soc Nephrol 2008; 19: 2001–2010.

Liu

Zhang

Liu

et al.

Multitarget therapy for induction treatment of lupus nephritis: A randomized trial. Ann Intern Med 2015; 162: 18–26.

Ikeuchi

Hiromura

Takahashi

et al.

Efficacy and safety of multi-target therapy using a combination of tacrolimus, mycophenolate mofetil and a steroid in patients with active lupus nephritis. Mod Rheumatol 2014; 24: 618–625.

Mok

. Combined low-dose mycophenolate mofetil and tacrolimus for lupus nephritis with suboptimal response to standard therapy: A 12-month prospective study. Lupus 2013; 22: 1135–1141.

Joo

Bae

. Assessment of clinical manifestations, disease activity and organ damage in 996 Korean patients with systemic lupus erythematosus: Comparison with other Asian populations. Int J Rheum Dis 2015; 18: 117–128.

Weening

D’Agati

Schwartz

et al.

The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004; 15: 241–250. Erratum in J Am Soc Nephrol 2004; 15: 835–836.

Hui

Garner

Rees

et al.

Lupus nephritis: A 15-year multi-centre experience in the UK. Lupus 2013; 22: 328–332.

10.

Xiong

Lahita

. Pragmatic approaches to therapy for systemic lupus erythematosus. Nat Rev Rheumatol 2014; 10: 97–107.

11.

Nomura

Shimizu

Kishimoto

et al.

Efficacy and safety of multitarget therapy with mizoribine and tacrolimus for systemic lupus erythematosus with or without active nephritis. Lupus 2012; 21: 1444–1449.

12.

Simonetta

Allali

Roux-Lombard

Chizzolini

. Successful treatment of refractory lupus nephritis by the sequential use of rituximab and belimumab. Joint Bone Spine 2016; 84: 235–236.

13.

Sjöwall

Hjorth

Eriksson

. Successful treatment of refractory systemic lupus erythematosus using proteasome inhibitor bortezomib followed by belimumab: Description of two cases. Lupus 2017; 26: 1333–1338.

14.

Mok

. Calcineurin inhibitors in systemic lupus erythematosus. Best Pract Res Clin Rheumatol 2017; 31: 429–438.

15.

Ekberg

Tedesco-Silva

Demirbas

et al.

Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007; 357: 2562–2575.

16.

Kajawo

Botha

FCJ

Okpechi

. Clinico-pathological features of repeat renal biopsies in patients with lupus nephritis at Groote Schuur Hospital, Cape Town. Lupus 2017; 26: 1339–1346.

17.

Medina-Rosas

Yap

Anderson

Touma

. Utility of urinary protein-creatinine ratio and protein content in a 24-hour urine collection in systemic lupus erythematosus: A systematic review and meta-analysis. Arthritis Care Res (Hoboken) 2016; 68: 1310–1319.