Ixekizumab trough concentrations in psoriasis: Paving the way towards personalised therapy: A cohort study

Abstract

Background

Biologics for psoriasis demonstrate varying clinical outcome in real-world practice, implying potential under- and overexposure.

Objectives

In this prospective cohort study we aimed to develop and validate an in-house sandwich-type enzyme-linked immunosorbent assay (ELISA) for ixekizumab (IXE), and to explore whether there is an exposure-response relationship in standard maintenance dose for IXE, and whether patient factors influence IXE exposure and clinical outcome.

Methods

This was a prospective, multicentric, cohort study in psoriasis patients treated with IXE according to standard dosing regimen (BIOLOPTIM-IXE). IXE trough concentrations (TCs) in sera collected at multiple timepoints were measured using an in-house immunoassay.

Results

Using MA-IXE117E12 and MA-IXE100F5-biotin as the capture and detection antibodies, respectively, an ELISA was developed with an exposure-response curve ranging from 10 to 0.16525 ng/mL. One hundred-fifteen steady-state serum samples from 48 patients (17 [35.4%] bio-experienced; median body weight, 81.5 kg) were measured. Optimal responders (Psoriasis Area and Severity Index [PASI] ≤ 2) had significantly higher TCs than suboptimal responders (PASI > 2) (median TCs, 4.4 and 3.0 μg/mL, respectively; p = 0.026). Median cohort IXE TC was 4.1 µg/mL [2.8−6.1]. An optimal steady-state IXE TC of 3.4 µg/mL was identified for clinical outcome defined by absolute PASI. Median TCs and absolute PASI were significantly lower and worse, respectively, in patients ≥ 90 kg (p < 0.001 and p = 0.013, respectively) and in bio-experienced subjects (p < 0.001 and p = 0.029, respectively).

Conclusions

This study identified an IXE exposure-response relationship and an optimal effective steady-state TC of 3.4 µg/mL in real-world psoriasis patients, revealing the potential of therapeutic drug monitoring in optimising IXE use.