Anti-Adalimumab Antibodies Purified from Juvenile Idiopathic Arthritis Patients: Kinetic Characterization Among Biosimilars

Abstract

The use of adalimumab biosimilars has become increasingly common in clinical practice, reflecting their growing acceptance and efficacy as therapeutic alternatives to reference biologics. However, studies investigating the molecular interactions between anti-adalimumab antibodies (AAA) elicited in patients and different adalimumab biosimilars remain limited. This study aims to characterize the kinetic interactions between purified AAA from pediatric patients with Juvenile Idiopathic Arthritis and three adalimumab formulations: the originator Humira^®, and the biosimilars GP2017 (Hyrimoz^®) and SB5 (Imraldi^®). For this purpose, adalimumab formulations were immobilized on a gold chip, and purified AAA were flowed to perform further kinetic analysis using the surface plasmon resonance (SPR) technology. Results showed that the K_D values for purified AAA from patients treated with biosimilars GP2017 (Hyrimoz^®) or SB5 (Imraldi^®) were comparable across all formulations tested, including the originator Humira^®. AAA interacted with Humira^®, Hyrimoz^®, and Imraldi^® with similar apparent affinity (10^-9 M > K_D > 10^-10 M); slight variations have been observed among patients, less among biosimilars. The similarity in K_D values across biosimilars and the originator supports the notion that, at the level of immunogenicity, biosimilars can be considered clinically comparable to the originator.

Keywords: adalimumab; anti-drug antibodies; biosimilars; juvenile idiopathic arthritis; surface plasmon resonance.

Figure 1

Scheme of anti-adalimumab antibodies (AAA) purification. Firstly, the resin is functionalized. Then, the serum is loaded, and a washing step allows to remove all the undesired and unbounded proteins. Lastly, the AAA are eluted.

Figure 2

Scheme of the study with anti-adalimumab antibodies (AAA) purification and kinetic characterization.

Figure 3

(A) Fitting with binding 1:1 model; (B) fitting with two state reaction model; (C) residuals for fitting A; (D) residuals for fitting B.

Figure 4

ka/kd graph for the 1:1 binding model summarizing the interactions between purified anti-adalimumab antibody fractions and the drugs Humira^® (red), Imraldi^® (black), and Hyrimoz^® (blue) in duplicate. K_D affinity constants (calculated as kd/ka ratio) are displayed on the diagonal lines.