The safety of pharmacological treatment options for lupus nephritis

ABSTRACT

Introduction: The management of lupus nephritis (LN) has changed significantly over the last 10 years due to emerging evidence from large randomised clinical trials that produced good quality data and guided the formulation of two key concepts: the induction of remission and the maintenance phase of immunosuppressive therapy.

Areas covered: Optimizing cyclophosphamide and glucocorticoid regimens and the introduction of mycophenolate mofetil for proliferative and membranous LN has been pivotal. Nevertheless, concerns remain about treatment toxicity especially long term glucocorticoid use and exposure to cumulative cyclophosphamide doses. Here we discuss the conventional and newer pharmacological options for managing LN focusing on drug safety and toxicity issues.

Expert opinion: The need for effective and less toxic treatments led to the development of the role of targeted biologic therapies in LN. However, evidence from the initial randomized controlled trials has been disappointing, although this reflects inadequate trial design rather than true lack of efficacy.

KEYWORDS:

• Safety
• treatment
• lupus nephritis
• cyclophosphamide
• biologics

Article highlights

• Lupus nephritis is one of the most common and severe manifestations of SLE and is associated with significant morbidity and mortality

• Treatment options are guided by the histologic classification of LN

• Induction immunosuppression with combination of CYC or MMF and steroids aims to minimize inflammation in the kidney, and should be followed by maintenance therapy usually MMF, AZA or Tacrolimus

• MMF is a viable alternative to CYC for induction therapy of both proliferative and membranous LN.

• Rituximab, abatacept, atacicept and ocrelizumab´s trials failed to reach their primary outcomes in LN.

• Rituximab may be used as add on therapy to induction regiments, for refractory disease or as steroid sparing agent.

• Data are now available to encourage the view that LN might be treated at diagnosis using B cell depletion and avoiding oral steroids.

This box summarizes key points contained in the article.

Declaration of interests

D Isenberg has consulted for a number of pharmaceutical companies in the past 5 years included Roche, Merck Serono, Eli Lilly and Glaxo Smith Kline. The honoraria offered are passed onto a local arthritis charity. D Isenberg is supported by the Biomedical Centre Award to University College Hospial/University College London. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.