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

Abstract

Summary 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.

Weighing in on weight‐based secukinumab dosing for psoriasis

“…Aiming to develop a TDM strategy for secukinumab in psoriasis, Soenen et al . confirmed the secukinumab underexposure in real‐world overweight patients and determined a minimal effective secukinumab threshold of 39·1 mg L –1 associated with achieving PASI ≤ 2 or ΔPASI ≥ 90% 9 …”

“…8 Aiming to develop a TDM strategy for secukinumab in psoriasis, Soenen et al confirmed the secukinumab underexposure in real-world overweight patients and determined a minimal effective secukinumab threshold of 39Á1 mg L -1 associated with achieving PASI ≤ 2 or DPASI ≥ 90%. 9 This trial provides high-quality evidence to support above-label dosing of secukinumab to improve treatment outcomes in an otherwise difficult-to-treat patient population. Notwithstanding the importance of these findings in optimizing dosing in overweight patients, the need for interventions for sustainable weight-reduction-directed lifestyle behaviour in this patient group should be emphasizednot merely to improve treatment outcomes, but rather as an opportunity to optimize psoriasis-related comorbidities and patients' overall health status.…”

Blocking interleukin‐17 in psoriasis: Real‐world experience from the PsoPlus cohort

“…Serum was prepared and stored at a minimum of 20°C until C t analysis in the Laboratory of Diagnostic and Therapeutic Antibodies, KU Leuven. C t s for SEC were measured as described previously 40 . C t s for IXE were determined by use of an in‐house‐developed, sandwich‐type enzyme‐linked immunosorbent assay.…”

“…C t s for SEC were measured as described previously. 40 C t s for IXE were determined by use of an in-housedeveloped, sandwich-type enzyme-linked immunosorbent assay. In the assay, IXE is captured between MA-IXE117E12 as coating antibody and biotinylated MA-IXE100F5 as detecting antibody, allowing quantification of IXE concentrations ranging from 0.5 to 80.0 μg/ml.…”

Exposure–response relationship of guselkumab and the potential of serum proteomics in identifying predictive biomarker candidates in psoriasis

“…10 Evidence favouring TDM of biologics in psoriasis is rising. [11][12][13][14][15] In order to implement TDM, a well-defined exposure-response relationship must be present.…”