Posterior segment inflammatory outcomes assessed using fluorescein angiography in the STOP-UVEITIS study

Mohammad Ali Sadiq, Muhammad Hassan, Rubbia Afridi, Muhammad Sohail Halim, Diana V Do, Yasir J Sepah, Quan Dong Nguyen, STOP-UVEITIS Investigators, Mohammad Ali Sadiq, Muhammad Hassan, Rubbia Afridi, Muhammad Sohail Halim, Diana V Do, Yasir J Sepah, Quan Dong Nguyen, STOP-UVEITIS Investigators

Abstract

Background: Although fluorescein angiography (FA) is a frequently used imaging modality in patients with non-infectious uveitis (NIU), it has not been reliably used for objective assessment of posterior segment inflammatory outcomes in these patients. In this index study we report the posterior segment inflammatory outcomes of two different doses of intravenous (IV) infusions of tocilizumab (TCZ), an IL-6 inhibitor, in eyes with NIU using a semi-quantitative FA scoring system.

Methods: STOP-Uveitis is a randomized, multi-center clinical trial conducted at 5 clinical centers across the United States. The study evaluated the role of TCZ in patients with NIU. Thirty-seven (37) patients with NIU were randomized into one of two treatment groups in a ratio of 1:1. Group 1 received IV infusions of 4 mg/kg TCZ and group 2 received IV infusions of 8 mg/kg TCZ. Infusions were given every 4 weeks in both groups until month 6 (primary endpoint). Posterior segment inflammatory outcomes were assessed by evaluating FA at baseline and month 6 by graders at a central reading center. A previously reported, semi-quantitative, scoring system for FA was used to assess signs that represent ongoing inflammatory processes in the posterior segment. These signs included optic disc hyperfluorescence, macular edema, retinal vascular staining and/or leakage, capillary leakage, retinal capillary nonperfusion, neovascularization of the optic disc, neovascularization elsewhere, pinpoint leaks, and retinal staining and/or subretinal pooling. Statistical significance was set at p < 0.05. Main outcome measures included change in posterior segment inflammation as assessed using FA at month 6.

Results: 37 eyes (37 patients) were randomized in the STOP-Uveitis study. 30 eyes were found to be eligible for this sub-study based on study criteria. Seven eyes had ungradable images at either baseline or month 6 and were therefore excluded from the analysis. The reduction in FA inflammatory scores at month 6 were statistically significant in both groups (p < 0.05). The difference between the two groups was not significant (p = 0.351).

Conclusions: IV infusions of tocilizumab (both 4 and 8 mg/kg) are effective in improving posterior segment inflammation in eyes with NIU. A semi-quantitative FA scoring system may be used as a reliable outcome measure for assessment of posterior segment inflammation.ClinicalTrials.gov Identifier: NCT01717170.

Keywords: Clinical trial; Fluorescein angiography; IL-6; Non-infectious; Tocilizumab; Uveitis.

Conflict of interest statement

Competing interestsYJS has received research support from Astellas, Genentech, and Optovue, and serves on the Scientific Advisory Board for Genentech/Roche, Optos, and Regeneron. QDN serves on the Scientific Advisory Board for AbbVie, Bayer, Genentech, Regeneron, and Santen, among others. QDN also chaired the Steering Committee for the STOP-Uveitis Study and was on the Steering Committee for other studies sponsored by Genentech and Regeneron. DVD serves on the Scientific Advisory Board for Allergan, Genentech, Kodiak, Regeneron, and Santen and she has received research support from Genentech and Regeneron. No other authors have received any financial funding or support.

© The Author(s) 2020.

Figures

Fig. 1
Fig. 1
Representative images from a study patient at: a Baseline, showing diffuse areas of capillary leakage and an area of disc hyperfluorescence (inflammatory score 8) and at; b Month 6, showing a significant improvement in capillary leakage and disc hyperfluorescence (inflammatory score 1)

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