Adalimumab Drug Monitoring and Treatment Adjustment to Drug Antibodies in Noninfectious Uveitis

• Published in: American journal of ophthalmology Vol. 268; pp. 306 - 311
• Main Authors: Pichi, Francesco, Smith, Scott D., AlAli, Sahar H., Neri, Piergiorgio
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-12-2024
• ISSN: 0002-9394; 1879-1891; 1879-1891
• DOI: 10.1016/j.ajo.2024.09.008

To explore the incidence of antibodies against adalimumab (AAA) development in noninfectious uveitis (NIU) and to examine the impact of treatment adjustment in nonresponders.
Retrospective case series.
In this single-center study of patients with NIU treated with adalimumab, blood samples for adalimumab and AAA were collected and therapeutic adjustments post-monitoring in non-responders were analyzed including changes in injection intervals, addition of conventional disease-modifying antirheumatic drugs (cDMARD), and treatment alterations to biologic DMARD. The main outcome measures were the proportion of patients with positive AAA and active uveitis, decrease of AAA at final follow-up by different therapeutic interventions.
Of 42 patients who underwent laboratory investigations at 17.9 months after adalimumab initiation, 22 (52.4%) patients who were nonresponders demonstrated AAA (1243 ng/mL) with a mean adalimumab trough level of 3.0 µg/mL, significantly lower than the mean drug levels of patients without AAA (11.8 µg/mL). Fifteen (35.7%) patients were receiving concurrent treatment with a second immunosuppressive agent, but the mean antibody level and the mean adalimumab level were not statistically significantly different from the monotherapy group (P = .13 and P = .34). Reduction in AAA levels and relapse management was greatest among nonresponders who were treated by increasing the adalimumab dose and adding an additional immunosuppressive drug (−3565 ng/mL), followed by patients who were shifted to a different biologic (−1153 ug/mL).
The presence of AAA was detected in 88% of nonresponder patients and was associated with undetectable adalimumab drug levels. This underscores immunogenicity as a major cause of loss of response in uveitis patients receiving biotherapies. Increasing the dose of adalimumab injections together with the addition of low-dose cDMARDs was the most effective adjustment in immunized nonresponders for whom the adalimumab drug concentration was low.