Abstract
Purpose :
This study aimed to investigate the association between circulating drug levels and anti-drug antibodies (ADAs), clinical response, and concurrent immunomodulatory treatment (IMT) in patients with non-infectious uveitis treated with TNF-α inhibitors.
Methods :
A retrospective study was conducted at the National Eye Institute. Patients who underwent anti-adalimumab or anti-infliximab immunoassay testing for the presence of ADAs were included. Chart review was performed for demographic and laboratory data.
Results :
Forty-two adalimumab and 12 infliximab patients were included. In the adalimumab group, mean duration since diagnosis and duration of therapy of 84.2 and 30.6 months, respectively. In the infliximab group, mean duration since diagnosis and duration of therapy was 92.5 and 20.9 months, respectively. 35.8% of all adalimumab patients had ADAs with a mean antibody level (MAL) of 97.3 AU/mL. No infliximab patients developed ADAs.
When divided based on clinical response, 54.8% of adalimumab patients were complete responders with a mean drug level (MDL) of 11.4 mcg/mL, 14.3% were partial responders with MDL 9.7 mcg/mL, and 30.9% were non-responders with MDL 6.8 mcg/mL. ADAs were present in 21.7% of complete responders (MDL 4.1 mcg/mL and MAL 73.4 AU/mL), 50% of partial responders (MDL 2.1 mcg/ML and MAL 250.2 AU/mL), and 53.8% of non-responders (MDL 2.2 mcg/mL and MAL 35.3 AU/mL). In the infliximab group, MDL was 27.2 mcg/mL.
MDL and MAL were also analyzed based on use of concurrent IMTs. ADAs were present in 20.0% of patients on mycophenolate mofetil, 38.5% on methotrexate, and 53.8% on monotherapy. MDL and MAL were 12.57 mcg/mL and 50.33 AU/mL for the mycophenolate group, 9.02mcg/mL and 42.8 AU/mL for methotrexate, and 6.78mcg/mL and 147.34 AU/mL for monotherapy, respectively.
Conclusions :
ADAs were observed in 35.8% of adalimumab and 0% of infliximab patients. In the adalimumab cohort, complete responders had a higher MDL and lower ADA compared to partial and non-responders. Notably, when antibodies were present, MDL was lower regardless of clinical response, suggesting that a complete clinical response is associated with higher drug levels even when ADAs are present. Lastly, patients who used IMTs concurrently had a higher MDL and lower frequency of ADA in the adalimumab group, suggesting a benefit over monotherapy. Additional research is required to better understand the impact of ADAs in non-infectious uveitis.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.