title: Optimizing the use of existing therapies in lupus.
abstract: The management of systemic lupus erythematosus (SLE) is complicated by heterogeneous clinical presentations, a lack of universally accepted tools for the measurement of disease activity and a lack of powerful, safe, specific targeted therapies. Current medical treatment of disease activity relies on glucocorticoids as well as agents including hydroxychloroquine (HCQ), mycophenolate mofetil (MMF) azathioprine (AZA), and less frequently cyclophosphamide. These agents are generally used in fixed, weight-based dosing regimens, and both incomplete response and adverse effects are common. An emerging literature in SLE and other inflammatory diseases in which these drugs are used suggests that improved patient outcomes could be achieved through a different approach to their use. Measurement of drug or metabolite concentrations has been shown in a number of studies to identify under- and over-dosing, predict efficacy and detect non-adherence to therapy, with positive associations between optimum drug or metabolite levels and improved outcomes. In this paper, we will review the literature regarding the measurement of HCQ, MMF, AZA and cyclophosphamide drug and metabolite levels in SLE and inflammatory disease, and make recommendations for future research that could facilitate improved outcomes for patients with SLE.
authors.affiliation: Centre for Inflammatory Diseases, Monash University School of Clinical Sciences, Melbourne, Victoria, Australia.
authors.forename: Lucy
authors.initials: L
authors.lastname: Croyle
authors.forename: Eric F
authors.initials: EF
authors.lastname: Morand
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006886:Hydroxychloroquine / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008134:Long-Term Care; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D007166:Immunosuppressive Agents; D006886:Hydroxychloroquine; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine
keywords: azathioprine; drug treatment; erythematous; hydroxychloroquine; mycophenolate; systemic lupus; systemic lupus erythematous