Monitoring Biologic Agents in Rheumatoid Arthritis


Biologics dose individualization should be used more often in clinical practice due to its direct benefit for patients with rheumatoid arthritis, researchers recommend.

In a new review article, researchers suggest that biologics dose individualization should be used more often in clinical practice due to its direct benefit for patients with rheumatoid arthritis. They also report that there are indirect benefits of using biologic agents until more cost-efficient approaches are established.

This study appears in the January 18 online issue of British Journal of Clinical Pharmacology.

Biologic agents are the newest class of drugs for treating rheumatoid arthritis and are genetically engineered to respond like natural proteins in the immune system. “Therapeutic drug monitoring” is a technique that analyzes the concentration of a drug in the blood and reports its value. A drug’s value is determined by using mathematical and pharmacokinetic principles to make conclusions about the best ways to optimize treatment for patients.

Led by Carla Bastida, Pharm.D., of Hospital Clinic Barcelona in Spain, an extensive literature review was conducted to explore two areas related to therapeutic drug monitoring of biologic agents for rheumatoid arthritis:  1) concentration-effect relationships and 2) pharmacokinetic-pharmacodynamic modeling to optimize drug regimens.

The following drugs were included in the review:  etanercept, infliximab, adalimumab, certolizumab, golimumab, rituximab, abatacept and tocilizumab. To quantify the importance of the relationship between a drug and its effect on pharmacokinetic behavior, various pharmacokinetic parameters were assessed including mAbs absorption, distribution, and clearance.  Covariates such as age, gender, weight, concomitant pathologies, and concomitant treatment were also evaluated for their impact on drug pharmacokinetic parameters.

The researchers found that clearance was the most important pharmacokinetic parameter and was moderated by age, weight, or gender for etanercept, rituximab, and adalimumab. Abatacept clearance was also affected by weight, while tocilizumab clearance was impacted by rheumatoid factor, HDL-cholesterol, gender, and body surface area.

Another key finding regarding pharmacokinetic parameters was that etanercept, infliximab and golimumab, and tocilizumab’s central volume were shown to be affected by race, weight, and total protein and albumin, respectively.

Other evidence suggested an impact of immunosuppressive agents on mAb pharmacokinetics and in particular, infliximab and adalimumab. However, the mechanisms for decreased mAb clearance could not be fully explained.

To date, there are approximately 10 biologic agents for rheumatoid arthritis. These agents work through four different mechanisms: 1) anti-TNF- agents, 2) B-cell depletion, 3) CTLA-4 – IgG fusion protein to inhibit interaction between T and antigen-presenting cells, and 4) IL-6-directed therapy, as IL-6 is overexpressed in many inflammatory diseases.

Despite the promise of biologic agents, some limitations should be noted. For example, there can be increased risk for infections like tuberculosis because biologics can inhibit certain cytokines, which in turn interfere with normal immune response. As such, pre-screening of latent tuberculosis should be conducted before biologics are prescribed and careful monitoring should continue throughout the course of therapy.  Other concerns about biologic agents are related to their high cost compared to other therapeutic options and insufficient clinical response to certain drugs in some patients.

“There is an obvious need to improve the risk to benefit ratio of these therapies. Due to the fact that safety and efficacy concerns have in part been related to serum drug concentrations and biologics present a high PK variability, drug monitoring is proposed as a favorable tool to optimize this ratio,” wrote Dr. Bastida and colleagues.



No external funding was received to carry out this research. A post-residency award from the Hospital Clinic Barcelona supported the lead author’s research.



Carla Bastida, Virginia Ruíz, Mariona Pascal, et al. “Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthritis,” British Journal of Clinical Pharmacology. Published online January 18, 2017. DOI: 10.1111/bcp.13192.


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