D1.131 - TRough levels In plasma of dUpilumab and Mepolizumab in Patients with severe astHma (TRIUMPH)
Background
Mepolizumab and dupilumab are biologics widely used to treat severe asthma and have been proven to be very effective. Their dosing is fixed, based on findings from phase 3 clinical trials. However, data on drug levels in well-controlled asthma patients remain scarce. Investigating these trough levels may have the potential to initiate personalized dosing intervals in patients with severe asthma thus optimizing both treatment outcomes and healthcare costs.
Objective
To evaluate plasma trough levels of mepolizumab and dupilumab in adults with stable, severe asthma, both at the registered dosing frequency and during extended dosing intervals, and to identify associated co-variables.
Method
We included adult patients with stable severe asthma receiving mepolizumab or dupilumab who participated in the BIRDIE trial (February–December 2024). Plasma trough levels were the primary outcome measure. Secondary outcome was the association of trough levels with co-variables. Statistical analyses included univariable and multivariable regression.
Design
A retrospective, observational study based on data from the BIRDIE trial, a randomized intervention study on biomarker-driven dosing interval extension of dupilumab and mepolizumab.
Results
37 patients were included (15 mepolizumab; 22 dupilumab). Average trough levels were 14.6 mg/L (mepolizumab 100mg/4wk), 31.4 mg/L (dupilumab 200mg/2wk), and 73.3 mg/L (dupilumab 300mg/2wk). Trough levels were lower in patients on extended dosing intervals. The results are shown in table 1. Comorbidities diabetes type II (n=1) and sleep apnea (n=1) were associated with higher resp. lower mepolizumab trough levels. FEV1 with higher dupilumab 200 mg levels. BMI and age were associated with higher resp. lower dupilumab 300 mg levels.
Conclusion
The TRIUMPH study is, to the best of our knowledge, the first to provide data on mepolizumab and dupilumab plasma trough levels in adults with severe asthma with registered and extended dose intervals. Our findings reveal a wide range of trough levels, mainly in dupilumab groups, in clinically stable asthma patients, which may suggest its potential clinical applicability. Our results contribute to a better understanding of the therapeutic window and may pave the way for more efficient biologic therapy for severe asthma patients. Further research is required to confirm and expand these findings and assess long-term impacts.
