Elsevier

Autoimmunity Reviews

Volume 13, Issue 2, February 2014, Pages 206-214
Autoimmunity Reviews

Review
Prednisone in lupus nephritis: How much is enough?

https://doi.org/10.1016/j.autrev.2013.10.013Get rights and content

Abstract

Objective

To assess the effectiveness and safety of a protocol using medium doses of prednisone to treat lupus nephritis.

Methods

Patients receiving the ‘Cruces-protocol cohort’ (CPC) were paired 1:2 with patients from the ‘historic cohort’ (HC). The CPC received medium doses of prednisone combined with methyl-prednisolone pulses, hydroxychloroquine and immunosuppressive drugs, usually cyclophosphamide. The HC received cyclophosphamide and high-dose prednisone. Partial and complete remission rates and glucocorticoid-related toxicity were assessed.

Results

15 CPC and 30 HC patients were analysed. The mean (SD) initial dose of prednisone was 22 (8) mg/d in the CPC vs. 49 (19) mg/d in the HC (p < 0.001). The 6-month mean (SD) cumulative dose of prednisone was 1.7 (0.5) g (average daily dose 9 mg) vs. 4.5 (2.1) g (average daily dose 25 mg), respectively (p < 0.001). The median cumulative dose of cyclophosphamide at six months was 3 (0–4.5) g in the CPC vs. 5 (0–16.8) in the HC (p < 0.001). 15/15 (100%) vs. 10/30 (33%) patients were treated with hydroxychloroquine (p < 0.001). At six months, 12/15 (80%) patients in the CPC achieved partial or complete remission vs. 14/30 (47%) in the HC (p = 0.015). At 12 months, 13/15 (87%) vs. 19/30 (63%) patients, respectively, were in complete or partial remission (p = 0.055). Toxicity attributable to glucocorticoids was observed in 1/15 (7%) vs. 20/30 (67%) patients, respectively (p < 0.0001).

Conclusion

A combination of medium-dose prednisone, methylprednisolone pulses, cyclophosphamide and hydroxychloroquine is at least as effective in achieving remission of lupus nephritis as regimes containing high-dose prednisone and causes less toxicity.

Introduction

Lupus nephritis (LN) is present in 35 to 40% of adults with systemic lupus erythematosus (SLE), being a well recognized factor of morbidity and mortality [1]. Several consensus guidelines focusing on the management of LN have been recently developed [2], [3], [4]. All agree in recommending a 3 to 6-month induction phase, followed by a maintenance phase of variable duration [2], [3], [4], [5]. The induction phase usually includes the combination of glucocorticoids with an immunosuppressive agent [6]. Different clinical trials have addressed the efficacy of immunosuppressive drugs, such as cyclophosphamide, azathioprine and mycophenolate mofetil [7], [8], [9], [10], [11], [12], [13]. Concomitant therapy with glucocorticoids, usually at high doses, is the rule; however the impact of steroids in both response and toxicity has been insufficiently analysed. Glucocorticoid schedules are only partially explained in most studies and dosages are frequently modified during the follow up [14].

Due to the lack of solid evidence supporting the use of high dose glucocorticoids and given our concern for adverse effects, our group has been using reduced doses of prednisone in the treatment of lupus, on the assumption that they can be as effective as and safer than higher doses. Our aim in this study is to address the effectiveness and safety of our therapeutic scheme in patients with LN.

Section snippets

Study design and patients

We designed a comparison study between two groups of patients with LN from the Lupus-Cruces observational cohort: those patients treated with a defined protocol using medium doses of prednisone at induction, the ‘Cruces-protocol cohort’ (CPC), and with at least one year of follow-up, were compared with those from the ‘historic cohort’ (HC), treated with a protocol similar to the National Institute of Health (NIH) scheme. Each of the 15 patients of the CPC was matched with two patients from the

Demographic and SLE-related variables

Forty-five patients were included in the analysis. The demographic and baseline clinical characteristics of the patients are shown in Table 2. At the time of the diagnosis of LN, the GFR, serum albumin levels, C3 values and the proportion of patients with anti-dsDNA antibodies were similar in both cohorts. Hematuria was almost universal. The mean 24 hour proteinuria was significantly higher in the HC. Three of 15 patients (20%) had hypertension in the CPC vs. 12/30 patients (40%) in the HC. The

Discussion

High-dose glucocorticoids, usually 1 mg/kg/d of prednisone for periods not shorter than 2 to 4 weeks with variable tapering schedules, have been the rule to treat severe manifestations of SLE whatever the accompanying immunosuppressive regime [13], [18], [19]. However, the basis for using such doses, the duration of therapy and the tapering schedule are essentially empirical [20], [21].

The anti-inflammatory properties of glucocorticoids mediated by transrepression at the genomic level [22] are

Competing interests

The authors declare that they have no competing interests.

Take-home messages

  • Although empirical, schemes containing high-dose prednisone are almost universally used for the induction therapy of lupus nephritis.

  • This study shows that combination therapy using medium-dose prednisone is associated with less glucocorticoid-related toxicity.

  • Our results also point to a quicker and sustained response in patients treated with medium-dose prednisone regimes.

Acknowledgements

Dr. Álvaro Danza was supported by a grant from the Universidad de la República (Uruguay).

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