Therapeutic drug monitoring in dermatology: the way towards dose optimization of secukinumab in chronic plaque psoriasis

Background: Despite the favorable efficacy profile of secukinumab, clinicians encounter varying clinical responses amongst patients potentially associated with under- and overexposure. As biologics are expensive, rational use is crucial and evident. Therapeutic drug monitoring could guide clinicians in their decision-making regarding treatment modifications. Objectives: In this multicentric, prospective study, we aimed to develop and validate a secukinumab immunoassay and searched for the therapeutic window in psoriasis patients. Methods: Secukinumab concentrations in sera from 78 patients with psoriasis at multiple timepoints at trough during maintenance phase were determined. At each hospital visit, the disease severity was assessed through the Psoriasis Area and Severity Index (PASI). Results: The combination of MA-SEC66A2 as capture antibody and MA-SEC67A9, conjugated to horseradish peroxidase (HRP), as detecting antibody, resulted in an in-house secukinumab immunoassay. After quantification, 121 serum samples were included for exposure-response analysis. Based on a linear mixed-effects model, secukinumab trough concentrations decreased with increasing body mass index (BMI). Based on receiver operating characteristic (ROC) analysis, a minimal effective secukinumab threshold of 39.1 mg/L in steady state could be deduced and was associated with a 92.7% probability of having an optimal clinical response (PASI≤2 or ∆PASI≥90%). Conclusions: Monitoring and targeting a secukinumab trough concentration of 39.1 mg/L may be a viable treatment option in suboptimal responders. In patients with higher BMI, weight-based dosing may be needed in order to prevent underexposure.

Jaar van publicatie:2022

Toegankelijkheid:Open