Aqueous humor interleukin-6 levels in uveitic macular edema: baseline characteristics from the phase 1 DOVETAIL study

Abstract

Purpose : Interleukin-6 (IL-6) is a proinflammatory cytokine involved in ocular diseases such as uveitis and uveitic macular edema (UME). Dysregulated IL-6 secretion can lead to blood-retinal barrier breakdown, vascular leakage, and formation of macular edema. This exploratory analysis studied the relationship between baseline (BL) IL-6 levels in aqueous humor (AH) and disease characteristics in patients with UME.

Methods : DOVETAIL is a phase 1, multicenter, nonrandomized, open-label, multi-part study investigating the safety, tolerability, efficacy, and pharmacokinetic/pharmacodynamic profile of intravitreal vamikibart (RG6179, an anti–IL-6 monoclonal antibody) in patients with diabetic macular edema and UME. This analysis focused on BL data of patients ≥18 years with UME (n=37), noninfectious uveitis, and macular edema (central subfield thickness [CST] ≥325 µm). AH (study eye) and serum samples were collected at BL before study drug administration. BL levels of IL-6 were determined with a high-sensitivity immunoassay, and the relationship between BL AH IL-6 and functional/anatomical features was explored.

Results : Preliminary results showed a range of BL AH IL-6 levels (median 122 pg/mL, range 0.28-4360 pg/mL) that were high compared with the available literature for controls (median range 1.29–40.4 pg/mL).^1–3 IL-6 levels were approximately 100-fold higher in AH compared with serum, suggesting local production. BL AH IL-6 levels were independent of anatomical uveitis subtypes (anterior, intermediate, posterior, and panuveitis) and disease activity states (active, minimally active, inactive). A weak positive correlation was seen between higher IL-6 levels and higher BL CST, indicating a potential association between IL-6 and UME disease severity. Higher AH IL-6 levels were seen in patients with subretinal fluid (SRF) vs those without SRF.

Conclusions : Consistent with previous studies, BL levels of AH IL-6 were high in patients with UME. Trends were seen between higher levels of AH IL-6 at BL and higher CST and presence of SRF. However, the sample size was small, so these trends need to be investigated further in a larger population to determine the clinical relevance of the findings.
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This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.