Update on the Treatment of Lupus Nephritis
Update on the Treatment of Lupus Nephritis
Purpose of review: Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities.
Recent findings: Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront.
Summary: Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.
The presence of renal involvement adversely affects the outcome of patients with systemic lupus erythematosus (SLE). Severe renal disease is associated with increased mortality, progression to end-stage renal disease (ESRD), and a higher risk of treatment-related complications and toxicities. Through elegant but small randomized trials at the National Institutes of Health (NIH) in the 1970s and 1980s, monthly intravenous pulses of cyclophosphamide along with low-dose corticosteroids led to decreased long-term progression to renal failure compared with high-dose steroids alone, and thus became the standard lupus nephritis therapy. Despite this progress, resistance to therapy, relapses, and treatment-related toxicities remained common.
The last decade has seen further progress in the treatment of lupus nephritis. Mycophenolate mofetil (MMF) has emerged as an effective induction and maintenance therapy in severe lupus nephritis. Rituximab (RTX), already approved by the US Food and Drug Administration for rheumatoid arthritis, has been evaluated in large randomized controlled trials (RCTs). Calcineurin inhibitors (CNIs), used widely in solid-organ transplant patients, have been studied in small RCTs as induction, maintenance, and add-on therapy. Physicians now have many therapeutic options based increasingly on the data generated from RCTs. This review will discuss the key studies that have contributed to this amazing progress in the treatment of lupus nephritis over the last decade.
Abstract and Introduction
Abstract
Purpose of review: Lupus nephritis occurs in as many as half of patients presenting with systemic lupus erythematosus and is a major predictor of morbidity and mortality in this patient population. Prior to the last decade, the treatment of lupus nephritis was largely limited to corticosteroids, high-dose alkylating agents, and azathioprine, and this therapy was broadly prescribed regardless of patient demographics, clinical presentation, or prior toxicities.
Recent findings: Over the last decade, new immunomodulatory agents have emerged as effective induction and maintenance therapies in lupus nephritis. With these options, physicians are able to individualize the treatment regimens in an attempt to maximize clinical benefit and minimize adverse events. Moreover, the influence of patient demographics on disease severity and response to treatment has come to the forefront.
Summary: Here, we review the recent progress made in the therapy of lupus nephritis with a focus on the randomized controlled trials which have demonstrated the efficacy of these new treatment regimens.
Introduction
The presence of renal involvement adversely affects the outcome of patients with systemic lupus erythematosus (SLE). Severe renal disease is associated with increased mortality, progression to end-stage renal disease (ESRD), and a higher risk of treatment-related complications and toxicities. Through elegant but small randomized trials at the National Institutes of Health (NIH) in the 1970s and 1980s, monthly intravenous pulses of cyclophosphamide along with low-dose corticosteroids led to decreased long-term progression to renal failure compared with high-dose steroids alone, and thus became the standard lupus nephritis therapy. Despite this progress, resistance to therapy, relapses, and treatment-related toxicities remained common.
The last decade has seen further progress in the treatment of lupus nephritis. Mycophenolate mofetil (MMF) has emerged as an effective induction and maintenance therapy in severe lupus nephritis. Rituximab (RTX), already approved by the US Food and Drug Administration for rheumatoid arthritis, has been evaluated in large randomized controlled trials (RCTs). Calcineurin inhibitors (CNIs), used widely in solid-organ transplant patients, have been studied in small RCTs as induction, maintenance, and add-on therapy. Physicians now have many therapeutic options based increasingly on the data generated from RCTs. This review will discuss the key studies that have contributed to this amazing progress in the treatment of lupus nephritis over the last decade.
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