Synthetic pharmacotherapy for lupus nephritis

ABSTRACT

Introduction: Lupus nephritis is a frequent complication and a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE).

Area covered: The main characteristics and mechanisms of action of the synthetic drugs more frequently used in lupus nephritis are described. Possible strategies aimed to reduce the potential adverse events without affecting efficacy are reported.

Expert opinion: Many synthetic immunosuppressive drugs used in lupus nephritis have a low therapeutic index. Good knowledge of their pharmacologic characteristics, mechanisms of action, and drug-to-drug interactions, coupled with a strategy aimed to increase immunosuppression in the active phases of SLE while reducing the dosage in quiescent periods can reduce the iatrogenic morbidity while maintaining efficacy. Biologic agent may allow to reduce the use or the dosage of synthetic immunosuppressive drugs.

KEYWORDS:

• Lupus nephritis
• glucocorticoids
• cyclophosphamide
• purine synthesis inhibitorscalcineurin inhibitors

Article highlights

• Corticosteroids and immunosuppressive drugs have significantly improved the patient and renal survival of lupus nephritis.

• The use of these agents is burdened by their toxicity, which cause frequent and severe side effects that may impair the quality of life of lupus patients.

• A policy based on the use of an aggressive treatment during the active phase of the disease, while reducing the drug dosage at achievement of remission, helps in reducing the toxicity.

• Careful attention to the pharmacokinetic and pharmacodynamic profiles of immunosuppressive agents can help to prevent adverse drug reactions.

• A number of new promising drugs, such as monoclonal antibodies, may further improve the efficacy and reduce the toxicity of the current treatments based on synthetic drugs.

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Declaration of interest

G Moroni has acted as consultant for/received advisor Fee from GlaxoSmithKline. 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.

Additional information

Funding

This paper was not funded