Concentration-Based Tapering of Adalimumab Could Reduce Cost in Treating RA

An editorial, recently published in Annals of the Rheumatic Diseases, discussed the results of a study that found that an adalimumab (Humira) concentration-based tapering strategy was not inferior to the conservative strategy, conducted over 26 weeks.

Therapeutic drug monitoring (TDM) aims to improve patient care through drug concentration measurement in order to adjust dose or dosing time intervals individually. The study being reported on was an open-label, randomized trial that compared an increasing dosing interval of adalimumab from 2 to 3 weeks with a standard-dose strategy in patients with rheumatoid arthritis (RA) with an adalimumab trough concentration more than 8 mg/L. The results showed that the tapering strategy performed as well as the conservative strategy over the course of the study.

Prior to this study, the same researchers found that a drug concentration between 5 and 8 mg/L was associated with a good clinical response, and strongly suggested that no additional improvement could be expected by increasing the dose by reducing the time interval in patients with trough concentration greater than 8 mg/L. These results could be seen as a step toward implementation of TDM in clinical practice, which may in turn provide cost-savings to patients with RA.

However, it is important to note that the target sample size was not reached in this study. The authors surmise that this could be due to some patients fearing a flare up, or because researchers were looking to taper the dose, patients did not want to be allocated to the conservative strategy arm.

The article cites 3 principle arguments in support of TDM of an anti—tumor necrosis factor treatment in rheumatic diseases: the first is the variability in drug concentration among patients; the second is the observation of a relationship between drug concentration and clinical response in responding patients; and third is the fact that a low dosage/concentration may result in decreased efficacy and increased risk of immunogenicity, while a high dosage/concentration may increase the risk of side effects.

The authors argue that rheumatologists have been primarily concerned with patients with refractory disease or adverse events, which requires a rapid therapeutic decision. With this study, it is the authors’ hope that rheumatologists now realize that some of their patients have high serum drug concentration when receiving the recommended dose, and that dose reduction is feasible. This result could have a major implication for rheumatologists and society, because TDM could lead to reduced costs for patients while maintaining clinical responses.

In order to provide a more cohesive argument with larger amounts of clinical data that proves dosing reduction could be possible in patients with RA, the authors advise that more studies should be done to reconfirm these findings before implementing TDM of biopharmaceuticals in clinical practice.