Clinical utility of therapeutic drug monitoring in biological disease modifying anti-rheumatic drug treatment of rheumatic disorders: a systematic narrative review

ABSTRACT

Introduction: Biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs) have improved the treatment outcomes of inflammatory rheumatic diseases including Rheumatoid Arthritis and spondyloarthropathies. Inter-individual variation exists in (maintenance of) response to bDMARDs. Therapeutic Drug Monitoring (TDM) of bDMARDs could potentially help in optimizing treatment for the individual patient.

Areas covered: Evidence of clinical utility of TDM in bDMARD treatment is reviewed. Different clinical scenarios will be discussed, including: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity.

Expert opinion: The limited available evidence does often not report important outcomes for diagnostic studies, such as sensitivity and specificity. In most clinical relevant scenarios, predictive value of serum (anti-) drug levels is absent, therefore the use of TDM of bDMARDs cannot be advocated. Well-designed prospective studies should be done to further investigate the promising scenarios to determine the place of TDM in clinical practice.

KEYWORDS:

• Inflammatory rheumatic diseases
• rheumatoid arthritis
• spondyloarthropathies
• biologicals
• biological disease modifying anti-rheumatic drugs
• therapeutic drug monitoring

Article highlights

• Therapeutic Drug Monitoring (TDM) of biological Disease Modifying Anti-Rheumatic Drugs (bDMARDs), using serum (trough) drug levels and anti-drug antibodies (ADA) has been suggested as tool to optimize the treatment of an individual patient with an inflammatory rheumatic disorder.

• Available evidence in different clinical scenarios in which TDM could be useful in patients with rheumatoid arthritis (RA) and spondyloarthropathies are reviewed in this article.

• Investigated clinical scenarios include: prediction of response after start of treatment, prediction of response to a next bDMARD in case of treatment failure of the first, prediction of successful dose reduction or discontinuation in case of low disease activity, prediction of response to dose-escalation in case of active disease and prediction of response to bDMARD in case of flare in disease activity.

• Existing evidence on the utility of TDM of bDMARDS was scarce and often of low quality. In most scenarios, serum (anti) drug levels are not predictive for clinical outcome and TDM has therefore no clinical utility thus far in bDMARD treated rheumatic diseases.

• A few clinical scenarios are worth investigating further using well-designed prospective studies.

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Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded