Antidrug Antibody Level Associated with TNFi Therapy Failure in Noninfectious Uveitis

The retrospective study reported the presence of ADAs was associated with lower drug levels, and higher ADA levels were associated with increased risk of TNFi therapy failure.

The formation of antidrug antibodies (ADAs) and its association with tumor necrosis factor α inhibitor (TNFi) therapy in patients with noninfectious uveitis was highlighted in new research.

The findings suggest the presence of ADAs was associated with lower drug levels, but higher ADA levels may be associated with an increased risk of TNFi treatment failure, making the rate of ADA formation an important therapeutic consideration when using the therapy in patients with noninfectious uveitis.

“These findings support consideration of drug and antibody level testing in patients receiving adalimumab who are experiencing therapy failure,” wrote corresponding author Shilpa Kodati, MD, National Eye Institute, National Institutes of Health. “Failure due to ADA formation is suggested if serum drug level is low or undetectable and ADA levels are elevated, in which case intraclass or interclass switching can be considered.”

Infliximab and adalimumab have both been shown to be effective in treating noninfectious uveitis, but despite the effectiveness of TNFis, few studies have investigated ADAs in patients with noninfectious uveitis. The aim of the current study was to investigate the frequency of ADAs and their association with circulating drug levels, clinical response, and concurrent treatment with antimetabolites in patients receiving either agent.

The retrospective, cross-sectional study included patients diagnosed with noninfectious uveitis who underwent testing from September 2017 to July 2021 at the National Eye Institute. Investigators performed serum drug level testing with reflex testing for ADA levels using an enzyme-linked immunosorbent assay-based platform.

Comparisons of drug and ADA levels between groups were performed using the nonparametric Kruskal-Wallis test. Multivariable analyses for patients receiving adalimumab were done using parametric analysis of variance models to assess the association of ADA with mean drug level.

A total of 54 patients were included in the study, of which 42 received adalimumab (mean age, 43.6 years; 25 female [59.5%]) and 12 received infliximab (mean age, 42.7 years; 7 male [58.3%]).

The adalimumab group had a mean drug level of 9.72 μg/mL and mean antibody level was 84.2 AU/mL. The ADA frequency was 35.7%, or 15 of 42 patients. They additionally found the mean drug level was lower in patients with ADAs compared with those without ADAs (mean, 2.8 μg/mL vs. 13.6 μg/mL; difference, 10.8 μg/mL; 95% CI, 8.3 - 13.2 μg/mL; P <.001). Meanwhile, the infliximab cohort had a mean drug level of 27.02 μg/mL and investigators detected no ADAs.

Investigators further analyzed the association of concurrent antimetabolite use with mean drug level and mean antibody level in the adalimumab cohort. When comparing mean drug level and mean antibody level in patients with concurrent antimetabolite use (n = 29) with those receiving adalimumab monotherapy (n = 13), there was a higher mean drug level with concurrent antimetabolite use (mean, 11.0 μg/mL vs. 6.8 μg/mL; difference, –4.2 μg/mL; 95% CI, –8.7 to 0.2 μg/mL; P = .06).

Multivariable models suggested that the presence of ADAs in patients receiving adalimumab was associated with a reduction in the mean drug level of -11.0 μg/mL (95% CI, -14.0 to -8.06 μg/mL; P <.001). For each 1-arbitrary unit increase in ADAs was associated with a -0.02 μg/mL (95% CI, -0.01 to -0.34 μg/mL) difference in mean drug level (P <.001).

A further analysis of a receiver operating characteristic (ROC) curve in the adalimumab group revealed that a drug level above the threshold of 2.7 μg/mL was associated with any positive (partial or complete) response to therapy. In comparison, a threshold antibody level less than 15.2 AU/mL was associated with any positive response, according to investigators.

The study, “Antidrug Antibodies to Tumor Necrosis Factor α Inhibitors in Patients with Noninfectious Uveitis,” was published in JAMA Ophthalmology.