In Noninfectious Uveitis, Antidrug Antibodies May Reduce Biologics’ Effect

If a patient presents low serum drug level and raised ADAs, intra- or inter-class switching may be needed.

Monoclonal antibodies have offered swift, effective treatment options for autoimmune disorders, including chronic uveitis, but biological agents may also be susceptible to reactions that involve production of anti-drug antibodies (ADAs). A cross-sectional study published in JAMA Ophthalmology demonstrates reduced serum medication levels in patients who develop ADAs.

In a cohort of 54 individuals with noninfectious uveitis (NIU), researchers found 15 of 42 (35.7%) treated with adalimumab displayed ADAs, and 0 of 12 who received infliximab developed the antibodies. Results also show lower drug levels in patients with ADAs — participants with complete response to therapy had mean (SD) medication intensity of 4.1(2.8) µg/mL, vs those with no ADAs at 13.4(5.1) µg/mL (P =.002). Patients who did not improve or worsened presented drug level only reaching 2.2(2.9) µg/mL compared with those having no ADAs, 12.2(5.5) µg/mL (P =.006).

Individuals in the infliximab group exhibited a mean serum drug intensity of 27.02(18.15) µg/mL.

Although ADAs were related to lower drug concentration, including in responders, the study cautions that a high degree of ADAs may cause therapy with tumor necrosis factor ɑ inhibitors (TNFis) to lose efficacy. “These findings support consideration of drug and antibody level testing in patients receiving adalimumab who are experiencing therapy failure,” the researchers explain. “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.”

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.

Reflex tests identified ADAs in 50% of partial responders, compared with 53.8% of patients who did not respond, and in 21.7% of the group with total resolution. Those who received an antimetabolite with a biologic exhibited higher mean drug level at 11.0(7.3) µg/mL compared with individuals in monotherapy 6.8(4.5), a significant difference (P =.06).

Multivariate analysis revealed a relationship between ADAs and lower average medication level, -11.0 µg/mL (95% CI, -14.0 to -8.06), as well as that each arbitrary unit (AU/mL) rise in ADA was linked to a -0.02 µg/mL loss for average medication level (P <.001). Further, receiver operating characteristic curve revealed complete or partial response was related to circulating medication more than a benchmark of 2.7 µg/mL, and ADA level less than 15.2 AU/mL.

In prior rheumatology studies, ADAs appeared as soon as 2 weeks to more than a year after starting a monoclonal antibody. Also, patients treated for rheumatoid arthritis who showed ADAs had a 68% decrease in response. In a meta-analysis representing 14,651 with systemic autoimmune illnesses, ADA incidence proportion using a TNFi was 12.7%. Regarding NIU, ADA rates with adalimumab were 2.7% to 5% in clinical trials, and 12.5% to 45% in smaller studies.

The current investigation was conducted from September 2017 to July 2021. Mean age in the adalimumab group was 43.6(19.6) years, and for infliximab, 42.7(20.4) years. Limitations comprised a retrospective design that encompassed variable testing intervals, and selection bias from including data for participants who did not respond to TNFis. Also, underestimation may have resulted from discontinuing a drug before testing when no initial response occurred. The infliximab group was small. However, there is scant research which examines ADA reaction in patients with NIU, and this analysis offers data with “one of the largest sample sizes” to date.

Disclosure: One study author declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Bellur S, McHarg M, Kongwattananon W, et al. Antidrug antibodies to tumor necrosis factor α inhibitors in patients with noninfectious uveitisJAMA Ophthalmol. Published online December 22, 2022. doi:10.1001/jamaophthalmol.2022.5584