Therapeutic monitoring of the immuno-modulating drugs in systemic lupus erythematosus

Abstract

Despite the emergence of newer immunomodulating agents for systemic lupus erythematosus (SLE), a substantial proportion of patients still do not respond optimally. While the mechanisms for the differential responses to drug therapy are unclear, variation in drug exposure with the same dosing protocol related to pharmacogenetic and pharmacokinetic factors may contribute. This article discusses the use of therapeutic drug monitoring (TDM) to optimize therapies in SLE patients. Areas covered: Evidence on the relationship between blood levels and efficacy/toxicity of immuno-modulating drugs such as hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) and the calcineurin inhibitors that are often used in SLE. Expert commentary: Current data suggest a correlation between exposure and efficacy of HCQ and MMF in SLE. The relationship between HCQ or MMF blood concentrations and their adverse effects requires further elucidation. The serum trough level of tacrolimus does not appear to correlate with clinical response in lupus nephritis but is associated with toxic effects. Owing to the paucity of data, the 'optimal' blood levels of these agents in SLE have yet to be determined by large population pharmacokinetic studies. Nevertheless, TDM enables early identification of non-adherence and over-exposure to these SLE medications so that dosing adjustment can be performed to minimize toxicities and wastage.

Keywords: Lupus; efficacy; immunosuppressive; pharmacogenetics; pharmacokinetic.