Therapeutic Drug Monitoring in Rheumatic Diseases
Rapid and effective suppression of inflammation is a primary goal in the treatment of rheumatic diseases. However, the therapeutic effect of most medications may be slow to manifest, in the order of weeks or months in the case of DMARDs. Monitoring of drug concentrations allows the possibility of appropriate dose adjustment or changes in medication to achieve more rapid or better outcomes. We review the evidence for drug concentration monitoring. Despite the theoretical utility for monitoring of MTX polyglutamate concentrations in red blood cells in patients with RA, studies have not shown a clear association between concentrations and either efficacy or toxicity and routine measurement is not yet recommended. Small studies associating disease control with concentrations of anti-TNF therapies and anti-drug antibodies suggest that routine monitoring may be useful in the future. However, the data are not yet sufficient for this recommendation. With the use of allopurinol in gout, there is a putative therapeutic range for the active metabolite oxypurinol; however, adjusting the allopurinol dose to achieve a target urate concentration is likely to be most effective, and measuring oxypurinol may be best suited to assessing drug adherence. Although measuring thiopurine metabolite concentrations with AZA therapy has been shown to be useful in IBD, studies in rheumatic diseases have so far failed to confirm a useful association between concentrations and disease control or drug toxicity. Whole blood concentrations of HCQ have been associated with disease control in SLE and future studies may be able to determine a therapeutic range.
Rapid and effective suppression of inflammatory disease activity in order to prevent irreversible joint or organ damage is a primary goal in the management of many rheumatic diseases. However, most DMARDs take some months to become effective and not all patients will respond to an individual DMARD. In RA, early introduction of DMARDs, early use of combination therapy, frequent disease activity assessment and therapeutic changes if necessary are all recommended with the aim of rapid disease control. However, these approaches still require the passage of time before a response can be determined, and even if the desired therapeutic effect is achieved, the patient may discontinue therapy due to the occurrence of adverse effects.
Pharmacogenomics and therapeutic drug monitoring (TDM) are two methods that may help determine whether an individual patient will respond to or have adverse effects associated with a particular drug. Within the field of rheumatic diseases only two pharmacogenetic tests have reached clinical practice. The thiopurine methyltransferase genotype has been associated with adverse effects to AZA and HLA-B*5801 has been associated with allopurinol hypersensitivity syndrome (AHS), particularly in Asian populations. TDM has received less attention and is the subject of this review.
Abstract and Introduction
Abstract
Rapid and effective suppression of inflammation is a primary goal in the treatment of rheumatic diseases. However, the therapeutic effect of most medications may be slow to manifest, in the order of weeks or months in the case of DMARDs. Monitoring of drug concentrations allows the possibility of appropriate dose adjustment or changes in medication to achieve more rapid or better outcomes. We review the evidence for drug concentration monitoring. Despite the theoretical utility for monitoring of MTX polyglutamate concentrations in red blood cells in patients with RA, studies have not shown a clear association between concentrations and either efficacy or toxicity and routine measurement is not yet recommended. Small studies associating disease control with concentrations of anti-TNF therapies and anti-drug antibodies suggest that routine monitoring may be useful in the future. However, the data are not yet sufficient for this recommendation. With the use of allopurinol in gout, there is a putative therapeutic range for the active metabolite oxypurinol; however, adjusting the allopurinol dose to achieve a target urate concentration is likely to be most effective, and measuring oxypurinol may be best suited to assessing drug adherence. Although measuring thiopurine metabolite concentrations with AZA therapy has been shown to be useful in IBD, studies in rheumatic diseases have so far failed to confirm a useful association between concentrations and disease control or drug toxicity. Whole blood concentrations of HCQ have been associated with disease control in SLE and future studies may be able to determine a therapeutic range.
Introduction
Rapid and effective suppression of inflammatory disease activity in order to prevent irreversible joint or organ damage is a primary goal in the management of many rheumatic diseases. However, most DMARDs take some months to become effective and not all patients will respond to an individual DMARD. In RA, early introduction of DMARDs, early use of combination therapy, frequent disease activity assessment and therapeutic changes if necessary are all recommended with the aim of rapid disease control. However, these approaches still require the passage of time before a response can be determined, and even if the desired therapeutic effect is achieved, the patient may discontinue therapy due to the occurrence of adverse effects.
Pharmacogenomics and therapeutic drug monitoring (TDM) are two methods that may help determine whether an individual patient will respond to or have adverse effects associated with a particular drug. Within the field of rheumatic diseases only two pharmacogenetic tests have reached clinical practice. The thiopurine methyltransferase genotype has been associated with adverse effects to AZA and HLA-B*5801 has been associated with allopurinol hypersensitivity syndrome (AHS), particularly in Asian populations. TDM has received less attention and is the subject of this review.