The potential value of blood monitoring of biologic drugs used in the treatment of rheumatoid arthritis

Abstract

The advent of biological therapies has been a major therapeutic advance in rheumatology. Many patients now enjoy improved quality of life through better disease control. The number of therapies continues to grow both within drug class (including biosimilar drugs) and via new mechanisms. For the first time, nonbiological drugs such as small-molecule inhibitors (Janus kinase inhibitors) have shown clinical equivalence. However, clinical unmet need remains with up to a third of patients commenced on a biologic therapy having minimal or no response: (a) Generally, the first biologic used secures the best response, with likelihood of remission falling thereafter with successive therapies; (b) the success of strategy trials using biological therapies can be difficult to replicate in clinical practice due to a combination of patient factors and service limitations. Accordingly, ensuring optimization of initial treatment is an important consideration before switching to alternatives. Therapeutic drug monitoring (TDM) is the measurement of serum levels of a biologic drug with the aim of improving patient care. It is usually combined with detection of any antidrug antibodies that could neutralize the effect of the therapy. This technology has the potential to be a form of ‘personalized medicine’ by individualizing therapy, in particular, dosing and likelihood of sustained treatment response. It requires a clear relationship between drug dose, blood concentration and therapeutic effect. This paper will outline the technology behind TDM and unpack what we can learn from our colleagues in gastroenterology, where the adoption of TDM is at a more advanced stage than in rheumatology. It will explore and set out a number of clinical scenarios where rheumatologists might find TDM helpful in day-to-day practice. Finally, an outline is given of international developments, including regulatory body appraisals and guideline development.

The First WHO International Standard for Adalimumab: Dual Role in Bioactivity and Therapeutic Drug Monitoring

“…A similar stance has been adopted by the British Rheumatology association but paradoxically, in Scotland, a national TDM service for adalimumab and infliximab has been introduced. In another development, the European League Against Rheumatism have set up a taskforce to review the evidence on TDM in RA with support from a recently launched clinical trial with the aim of providing recommendations or advice to clinicians (76).…”

Impact of immunogenicity on clinical efficacy and toxicity profile of biologic agents used for treatment of inflammatory arthritis in children compared to adults

“…In addition, the large variability of ADA levels against biologic agents detected in various adult and paediatric studies of inflammatory arthritis is very likely influenced by the sensitivity of the assay used, concomitant MTX dose, time point of sample collection, as well as patients’ characteristics (genetic background, smoking, age). The overall impact of ADAs on drug efficacy, as well as therapeutic drug monitoring, are particularly relevant in guiding future therapeutic strategies of tapering biologic treatments in inflammatory arthritis patients, 102 , 104 although further research related to their impact on clinical decision making is required. 16 , 84 …”

The Evolving Role of Microsampling in Therapeutic Drug Monitoring of Monoclonal Antibodies in Inflammatory Diseases

“…The optimal concentration is specific for each mAb, disease indication, dosing regimen and treatment time-point. To date, several reviews have summarized the studies assessing the exposure-response relationships and optimal concentration thresholds for mAbs in inflammatory diseases [ 22 , 23 , 24 , 25 , 26 ]. It seems the consensus and guidelines for TDM and target mAb concentrations are best established in the field of Gastroenterology, but the advances are continuously made in the management of rheumatic and dermatologic conditions, as well ( Table 1 ) [ 23 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ].…”

“…The presence of ADAs indicates an immune-mediated nonresponse due to drug immunogenicity, which might be avoided by switching the therapy to another mAb from the same class. In contrast, the absence of ADAs together with suboptimal drug concentration indicate a non-immune mediated pharmacokinetic nonresponse, which might be overcome by dose adjustment, to achieve higher exposure and drug concentration, at which the patient is more likely to respond to treatment [ 19 , 23 , 26 , 27 , 28 , 37 ].…”