Immunogenicity of adalimumab in patients with noninfectious uveitis based on therapeutic drug monitoring.

BACKGROUND

To evaluate the utility of therapeutic drug monitoring (TDM) in adalimumab-treated noninfectious uveitis (NIU) patients and determine the prevalence, incidence, and risk factors for anti-adalimumab antibody (AAA) development.

METHODS

In this retrospective cohort study, the frequency of AAA development, the association between serum drug concentrations and clinical efficacy, and the clinical utility of TDM were evaluated in NIU patients treated with adalimumab (ADA). Eligible patients were divided into a TDM group, in which serum ADA and AAA levels were measured prior to dosing and the treatment regimens were adjusted accordingly, and a control group, in which management was based on clinical judgement. Treatment responses were systematically assessed in both groups throughout the follow-up.

RESULTS

We established a therapeutic trough concentration window of 2.9–5.8 µg/mL for ADA in NIU patients, with serum trough levels exceeding 8 µg/mL suggesting a potential “ceiling effect.” Overall, patients managed with TDM achieved significantly better clinical outcomes than those without TDM: the median time to inflammation remission was shorter (28 days vs. 42 days), the recurrence rate was lower (15% vs. 42%), and the incidence of adverse events was reduced (10% vs. 31%). TDM guidance was implemented for 20 patients (51.3%), with the remaining 19 (48.7%) serving as controls without TDM guidance. Among the 20 patients managed with TDM guidance, six patients (30.0%) who demonstrated inadequate clinical response to adalimumab after at least six months of therapy were classified as nonresponders. Anti-adalimumab antibodies (AAAs) were detected in 3 patients among the nonresponders, with a median concentration of 1041 ng/mL (range: 578.1–1844.3 ng/mL). These patients presented significantly lower adalimumab trough concentrations (median: 0.55 µg/mL) than AAA-negative patients (median: 3.43 µg/mL; p < 0.001). After TDM guidance, the median adalimumab concentration in nonresponders increased to 1.22 µg/mL, whereas the AAA concentration decreased to 894 ng/mL (range: 0–1197.8 ng/mL). Concurrently, nonresponders demonstrated measurable improvements in key clinical outcomes, including best-corrected visual acuity, central macular thickness, and standardized ocular inflammation grading scores.

CONCLUSION

TDM of adalimumab using practical serum sampling protocols is clinically feasible and has potential benefits for patient management. AAAs were detected in 50% of nonresponders and were associated with lower concentrations of adalimumab. This study provides the first protocolized evidence for TDM implementation for NIU, addressing a critical gap in current uveitis management guidelines.