Therapeutic drug monitoring that includes the measurement of trough concentrations and anti-drug antibodies, along with clinical response, is a tool for clinical decision making.
TDM can assist with making targeted dose adjustments in patients with low drug concentrations, monitoring of adherence, and assessment of patients who lose response, or who do not respond at all. The interest in TDM is spurred by the need for evidence-based and cost-effective use of biologics, given the high prevalence of psoriasis, the impact on patients’ lives, and the cost of the therapy, the authors wrote.
The precise underpinnings of how psoriasis develops is not fully understood, but other studies have shown there is a complex relationship between the innate and adaptive immune system as the disease progresses in response to an unidentified trigger; the trigger can be genetic, environmental, or immunologic.
Despite the development of medications targeting tumor necrosis factor as well as interleukin (IL)-23, IL-22 and IL-17, not all patients respond to therapy, or they may stop responding over time.
The researchers conducted a literature review on the TDM of TNF alpha antagonists (adalimumab, infliximab, and etanercept), IL12/23 antagonists (usekinumab, guselkumab, and tildrakizumab) and IL-17 inhibitors (secukinumab, ikekizumab) as well as biosimilars. While target therapeutic ranges for biologics are preferred, so far this has only been explored in adalimumab, the researchers said.
For adalimumab, the incidence rates of anti-adalimumab antibodies in psoriasis have ranged from 6.5% to 45%. The most recent report of a therapeutic range for adalimumab trough levels range from 3.51-7.00 mg/L.
For etanercept, the researchers wrote that it appears to exhibit immunogenicity less often than other biologics, with anti-etanercept antibodies observed in 0%-18.3% of patients.
For ustekinumab, anti-ustekinumab antibodies (AUA) have been reported in 3.8%-6.0% of patients. In addition, serum ustekinumab concentrations are affected by weight, with lower serum concentrations observed in heavier patients.
The researchers said additional research is needed, especially for newer biologics, to evaluate target therapeutic ranges. For instance, little is known about the TDM of secukinumab and ixekizumab; both selectively bind and neutralize interleukin-17A, the primary effector of Th17 cells. The same is true of guselkumab and tildrakizumab, which target interleukin-23.
While the researchers said they recommend the measurement of biologic serum trial concentrations and anti-drug antibody levels in routine clinical practice when possible, they noted that can be challenging, especially if patients take medication in the office but may skip doses in between visits.
Liau MM, Oon HH. Therapeutic drug monitoring of biologics and psoriasis (published online July 5, 2019). Biologics. doi: 10.2147/BTT.S188286.