Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis

Arends, Suzanne; Grootscholten, Cecile; Derksen, R. H. W. M.; Berger, Stefan P.; Sévaux, R.G.L. de; Voskuyl, Alexandre E.; Bijl, Marc; Berden, Jo H. M.

doi:10.1136/annrheumdis-2011-200384

Cited by 63 publications

(33 citation statements)

References 26 publications

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“…Based on the results of controlled trials and their extended follow-up,21 35 91 it is recommended that the duration of maintenance treatment in lupus nephritis should be at least 3 years. This is also supported by observational studies showing that early (before 18–24 months after achieving response) tapering or discontinuation of immunosuppressive treatment is associated with increased risk (RR 2.6) for renal flares 92 93.…”

Section: Resultsmentioning

confidence: 99%

Treat-to-target in systemic lupus erythematosus: recommendations from an international task force

et al. 2014

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The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet points were analysed for degree of agreement among the task force. The Oxford Centre level of evidence (LoE, corresponding to the research questions) and grade of recommendation (GoR) were determined for each recommendation. The 12 systematic literature searches and their summaries led to 11 recommendations. Prominent features of these recommendations are targeting remission, preventing damage and improving quality of life. LoE and GoR of the recommendations were variable but agreement was >0.9 in each case. An extensive research agenda was identified, and four overarching principles were also agreed upon. Treat-to-target-in-SLE (T2T/SLE) recommendations were developed by a large task force of multispecialty experts and a patient representative. It is anticipated that 'treating-to-target' can and will be applicable to the care of patients with SLE.

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Section: Resultsmentioning

confidence: 99%

Treat-to-target in systemic lupus erythematosus: recommendations from an international task force

et al. 2014

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“…However, cyclophosphamide has both instant and cumulative adverse effects, including marrow suppression, gonadal toxicity, hemorrhagic cystitis, and the increased risk of cancer as well as the possibility of no response or relapse in several patients (Houssiau et al 2002, 2010a). Therefore, other therapeutic agents, such as azathioprine and mycophenolate mofetile with few toxic effects, come prior to other alternatives (Grootscholten et al 2006; Arends et al 2012; Sahin et al 2008; Houssiau et al 2010b; Dooley et al 2011). …”

Section: Introductionmentioning

confidence: 99%

Efficacy of long-term maintenance therapy with mycophenolate mofetil in lupus nephritis

Rezaieyazdi

Tavakoli²,

Khajehdaluee

et al. 2014

SpringerPlus

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BackgroundMycophenolate mofetil (MMF) has long been used to manage lupus nephritis. Despite research on its long-term efficacy, it is still warranted to conduct further investigation regarding its indications, safety and outcome. This study was intended to evaluate our proposed protocol in maintenance therapy with MMF.Twenty-four lupus nephritis patients were registered prior to their receiving 3–6 month induction therapy with monthly iv pulses of cyclophosphamide (CYC), followed by 24 month maintenance therapy using MMF and steroid. We defined end points as achievement of complete and partial remission, relapse, refractory to therapy as well as end stage renal disease (ESRD) and death. Friedman and repeated measurement tests were used to assess the effect of treatment on parameters over time.Complete renal remission was achieved in 79.16% until the end of the last follow up with an average period of 12.45 ± 7.37 months since treatment commenced. Significant statistical differences were seen regarding proteinuria, hematuria, leukocyturia, plasma creatinine, C3, C4 before and after therapy (P < 0.05): plasma creatinine and proteinurea falling from 0.96 ± 0.65 to 0.75 ± 0.19 mg/dl (P < 0.14) and from 1.64 ± 1.12 to 0.27 ± 0.60 gr/24 h (P < 0.001). By the end of 24-month, 95.8% of patients had been in remission. Four episodes of relapse ended in remission followed by retreatment. No life-threatening side effects were observed in 66.6% of patients with fourteen cases of infection (58.3%). None of them developed ESRD.Maintenance therapy with MMF was shown to yield favorable outcome with minimal complications, in treating lupus nephritis (IRCT2012071710313N1).

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“…91 In spite of these findings, serum creatinine levels and proteinuria were similar in the two groups, and at long-term follow-up (median 9.6 years), no statistically significant differences were evident between the two groups with regard to the rate of doubling of serum crea tinine, ESRD or mortality. 93 However, rates of serum creatinin e d oubling (16% versus 8%) and death (16% versus 10%) were numerically higher in the azathioprine group than in the cyclophosphamide group. 93 These results suggest that azathioprine, even when combined with methylprednisolone pulses, might not be sufficient to ensure sustained remission and prevent renal scarring in patients with aggressive disease, but might have a role in patients with mild to moderate lupus nephritis.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 96%

“…93 However, rates of serum creatinin e d oubling (16% versus 8%) and death (16% versus 10%) were numerically higher in the azathioprine group than in the cyclophosphamide group. 93 These results suggest that azathioprine, even when combined with methylprednisolone pulses, might not be sufficient to ensure sustained remission and prevent renal scarring in patients with aggressive disease, but might have a role in patients with mild to moderate lupus nephritis.…”

Section: Calcineurin Inhibitorsmentioning

confidence: 96%

Treatment of severe lupus nephritis: the new horizon

Chan

2014

Nat Rev Nephrol

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Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

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Long-term follow-up of a randomised controlled trial of azathioprine/methylprednisolone versus cyclophosphamide in patients with proliferative lupus nephritis

Cited by 63 publications

References 26 publications

Treat-to-target in systemic lupus erythematosus: recommendations from an international task force

Treat-to-target in systemic lupus erythematosus: recommendations from an international task force

Efficacy of long-term maintenance therapy with mycophenolate mofetil in lupus nephritis

Treatment of severe lupus nephritis: the new horizon

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