Cyclophosphamide and Lupus Nephritis: When, How, For How Long?

Abstract

Ever since the introduction of cyclophosphamide (CY), the management of lupus nephritis has dramatically changed, and its prognosis has greatly improved. Based on randomized controlled trials and long-term observational studies, pulse therapy with CY in combination with methyl-prednisolone (MP) is the "gold standard" of therapy for severe lupus. The realization of the significant gonadal toxicity intensified the efforts for the development of alternative immunosuppressive agents. In a large, randomized controlled trial, newer agents such as mycophenolate mofetil (MMF) have demonstrated comparable efficacy and less toxicity for moderately severe disease. To date, combinations of monthly pulses of CY with MP remain the gold standard for the induction of remission in severe lupus. For maintenance, less toxic agents such as azathioprine or MMF are equally effective and are routinely used in the current therapy of lupus.

Cyclophosphamide in dermatology

“…4 Cumulative doses associated with pulmonary toxicity range from 30-250 g. 52 Table 3 summarises considerations and recommendations for monitoring and preventing side-effects of cyclophosphamide therapy, derived from rheumatological and dermatological papers. 30,31,54 CONTRAINDICATIONS Absolute contraindications include pregnancy and breastfeeding women, patients in whom conserving fertility is a concern, drug hypersensitivity, bone marrow depression and a previous history of bladder cancer. 8 Relative contraindications include active infection and impaired hepatic or renal function.…”

“…Monitoring and prevention recommendations/considerations (adapted from guidelines for ANCA-associated vasculitide, lupus nephritis and pemphigus vulgaris)30,31,54 …”

Neuropsychiatric Systemic Lupus Erythematosus

“…Severe NPSLE manifestations, mainly CNS involvement like cerebrovascular disease due to inflammation and transverse myelitis, has been treated with cyclophosphamide. There are different regimens of cyclophosphamide, which are mainly studied for treatment of lupus nephritis [ 97 ]. Cyclophosphamide can be given as monthly intravenous (500–1000 mg/m 2 ) doses for a 6-month induction period followed by quarterly maintenance doses for a period of 2 years [ 55 , 98 ]; however, studies have shown that immunosuppressives with less toxicity can be used for maintenance.…”

Extended follow-up of the CYCLOFA-LUNE trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide or on cyclosporine A

“…malignancy, infertility) that may manifest years after the initial exposure. 11,12 It is therefore essential to report outcomes from extended follow-up periods of the former clinical trial cohorts to assess the long-term risk-benefit ratio of the respective therapeutic regimens. In the investigator-initiated randomized controlled trial CYLOFA-LUNE 13 we tested the hypothesis that an immunosuppressive regimen based on cyclosporine A (CyA) may have similar efficacy, but greater safety, than that based on cyclophosphamide (CPH).…”