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

Abstract

Background: Despite the favourable efficacy profile of secukinumab, clinicians encounter varying clinical responses among patients potentially associated with under- and overdosing. As biologics are expensive, their rational use is crucial and evident. Therapeutic drug monitoring could guide clinicians in making decisions about treatment modifications. Aim: In this multicentre, prospective study, we aimed to develop and validate a secukinumab immunoassay and searched for the therapeutic window in patients with psoriasis. Methods: We determined secukinumab concentrations at trough in sera from 78 patients with psoriasis at multiple timepoints (Weeks 12, 24, 36, 48 and 52; after Week 52, measurements could be taken at an additional three timepoints) during maintenance phase, using an in-house secukinumab immunoassay consisting of a combination of MA-SEC66A2 as capture antibody and MA-SEC67A9, conjugated to horseradish peroxidase, as detecting antibody. At each hospital visit, disease severity was assessed using the Psoriasis Area and Severity Index (PASI). Results: After quantification, 121 serum samples were included for dose–response analysis. Based on a linear mixed-effects model, secukinumab trough concentrations were found to decrease with increasing body mass index (BMI). Based on receiver operating characteristic (ROC) analysis, we concluded that the minimal effective secukinumab threshold was 39.1 mg/L in steady state, and that this was associated with a 92.7% probability of having an optimal clinical response (PASI ≤ 2 or reduction in PASI of ≥ 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 underdosing.