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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.

SUBMITTER: Perry M

PROVIDER: S-EPMC7011331 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Perry Martin M Abdullah Azhar A Frleta Marina M MacDonald Jonathan J McGucken Andrew A

Therapeutic advances in musculoskeletal disease 20200207

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 <i>via</i> 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 comm ...[more]

PMID: 32095163

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Project description:Objective: use comprehensive molecular profiling to understand the molecular mechanisms that affect clinical response to anti-TNF therapy in rheumatoid arthritis (RA) and to identify predictive markers to differentiate good responders and non-responders. Methods: two independent cohorts of 40 and 36 biologic-naïve RA patients were selected from the Corrona (Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory coNditions) CERTAIN registry and categorized by EULAR response criteria. Whole-blood RNA and plasma samples from baseline and after 3 months of anti-TNF treatment were profiled using RNA-seq, shotgun proteomics and glycopeptide analysis. A cell type-specific transcriptional data analysis was applied to RNA-seq data to evaluate the impact of the most common immune cell sub-populations. Results: a treatment-related molecular signature was identified that showed a high level of correlation (ρ=0.62; permutation p<0.01) between cohorts. Treatment led to a reduction of neutrophils, independent of the status of response. Gene expression differences between good responders and non-responders at baseline did not manifest statistically significant concordance genome-wide between the two cohorts. However, a cell type-specific analysis indicated increased representation of innate cell type signatures in good responders and, conversely, increased expression of adaptive cell type signatures in non-responders at baseline in both cohorts. This result was confirmed by applying the cell-type specific analysis to other publicly available RA datasets. Evaluation of the neutrophil to lymphocyte ratio (NLR) at baseline in the remaining patients (n=1962) from the CERTAIN database using a logistic regression model further confirmed the observation (odds ratio of good/moderate response = 1.20 [95% CI = 1.03 – 1.41; p = 0.02]). Conclusion: differences in innate/adaptive immune cell type composition at baseline may be a major contributor to response to anti-TNF treatment within the first 3 months of therapy.

Dataset Information

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

Publications

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

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