Longitudinal monitoring of adalimumab levels and anti-adalimumab antibodies in Chinese patients with ankylosing spondylitis: a prospective cohort study

Abstract

This study aimed to clarify the association between longitudinal adalimumab concentrations, anti-adalimumab antibodies (AAA) levels, and clinical response in Chinese patients with ankylosing spondylitis (AS). A prospective multi-center, observational cohort study of AS patients receiving adalimumab therapy was conducted. Disease activity was assessed with the AS Disease Activity Score (ASDAS), and clinical responders were defined based on ASDAS improvement together with C-reactive protein normalization. Adalimumab concentrations were measured using a validated sandwich immunoassay. Measurement of AAA levels was performed with a laboratory-developed immunoassay system integrating electrochemiluminescence technology with specific immunomagnetic separation, with result reported as signal-to-noise ratio (S/N). A total of 140 patients receiving adalimumab monotherapy were included. The median follow-up period was 169 days, and 711 plasma samples were available for adalimumab concentrations and AAA levels measurements. Seven patients had pre-existing AAA, and 120 (90.2%) of the remaining 133 patients tested positive for AAA during follow-up. A total of 48 patients were excluded from the exposure–response relationship dataset owing to pre-existing AAA (n=7), lack of active disease (n=26), incomplete follow-up (n=8), and prolonged dosing intervals (n=7). Among the remaining 92 patients, a total of 58 (63%) achieved clinical response. Adalimumab concentrations were higher, and AAA levels were significantly lower, in responders compared with non-responders at multiple time points. Exposure–response relationship models also revealed a steady-state adalimumab concentration target of 5.1 μg/mL and a week-4 concentration target of 3.3 μg/mL, corresponding to an 80% probability of clinical response. Thirty-six of 92 patients (39.1%) exhibited AAA-S/N values exceeding the putative clinically meaningful threshold (AAA-S/N=10). Patients in the high-AAA group (AAA-S/N≥10) had lower drug levels (median: 1.5 μg/mL vs. 6.9 μg/mL, P< 0.0001) and poorer response rates (38.8% vs. 78.6%, P  = 0.0002), relative to those in the low-AAA group (AAA-S/N<10). Furthermore, patients who were week-4 AAA-positive exhibited a 1.8-fold increased risk of non-response (relative risk, 95% confidence interval, 1.1–2.8). Our results demonstrate that longitudinal profiles of adalimumab concentrations and AAA levels show a strong association with clinical responses in this Chinese AS cohort, which may inform therapeutic drug monitoring–guided adalimumab treatment strategies that remain to be further validated. ClinicalTrials.gov (NCT04875299).