The Efficacy and Safety of Adalimumab in Non-infectious Anterior Pediatric Uveitis With Peripheral Vascular Leakage

Summary

Children with anterior uveitis are prone to suffer from chronic recurrent course of intraocular inflammation and adverse effects of glucocorticosteroids (GCs) /immunomodulatory treatment (IMT) agents. The performance of adalimumab has been shown to be fairly favorable in treating refractory non-infectious uveitis. This study aims to assess the efficacy and safety of adalimumab for inflammatory flare prevention in non-infectious anterior pediatric uveitis with peripheral vascular leakage compared with methotrexate. Children weighed ≥ 30kg and aged between 4-16 years old with active chronic non-infectious anterior uveitis with peripheral retinal vascular leakage on ultra wildfield fluorescence fundus angiography (UWFFA) will be included. They will be treated with a predesigned inflammatory control regimen to reach inflammatory quiescence in 1 month. After that they will be treated with either MTX or adalimumab and regularly followed up for at least 6 months. The primary endpoint is treatment failure defined as any inflammatory fare with anterior chamber cell count grading increased from 0 to 1. Secondary endpoints are best corrected visual acuity (BCVA), inflammation parameters (keratic precipitates, vitreous haze grades), extent of vascular leakage, frequency of topical steroid eyedrops, systemic immunosuppressive drug load, and adverse events.

Timeline

Start

2021-08-19

Primary completion

2022-07

Completion

2023-07

Publications

• Background Agrawal R, Agarwal A, Jabs DA, Kee A, Testi I, Mahajan S, McCluskey PJ, Gupta A, Palestine A, Denniston A, Banker A, Invernizzi A, Fonollosa A, Sharma A, Kumar A, Curi A, Okada A, Schlaen A, Heiligenhaus A, Kumar A, Gurbaxani A, Bodaghi B, Islam Shah B, Lowder C, Tappeiner C, Muccioli C, Vasconcelos-Santos DV, Goldstein D, Behra D, Das D, Makhoul D, Baglivo E, Denisova E, Miserocchi E, Carreno E, Asyari F, Pichi F, Sen HN, Uy H, Nascimento H, Tugal-Tutkun I, Arevalo JF, Davis J, Thorne J, Hisae Yamamoto J, Smith J, Garweg JG, Biswas J, Babu K, Aggarwal K, Cimino L, Kuffova L, Agarwal M, Zierhut M, Agarwal M, De Smet M, Tognon MS, Errera MH, Munk M, Westcott M, Soheilian M, Accorinti M, Khairallah M, Nguyen M, Kon OM, Mahendradas P, Yang P, Neri P, Ozdal P, Amer R, Lee R, Distia Nora R, Chhabra R, Belfort R, Mehta S, Shoughy S, Luthra S, Mohamed SO, Chee SP, Basu S, Teoh S, Ganesh S, Barisani-Asenbauer T, Guex-Crosier Y, Ozyazgan Y, Akova Y, Habot-Wilner Z, Kempen J, Nguyen QD, Pavesio C, Gupta V; Collaborative Ocular Tuberculosis Study (COTS) Group. Standardization of Nomenclature for Ocular Tuberculosis - Results of Collaborative Ocular Tuberculosis Study (COTS) Workshop. Ocul Immunol Inflamm. 2020 Sep 30;28(sup1):74-84. doi: 10.1080/09273948.2019.1653933. Epub 2019 Dec 10.
• Background Nussenblatt RB, Peterson JS, Foster CS, Rao NA, See RF, Letko E, Buggage RR. Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis: a multicenter noncomparative interventional case series. Ophthalmology. 2005 May;112(5):764-70. doi: 10.1016/j.ophtha.2004.12.034.
• Background Tugal-Tutkun I, Herbort CP, Khairallah M; Angiography Scoring for Uveitis Working Group (ASUWOG). Scoring of dual fluorescein and ICG inflammatory angiographic signs for the grading of posterior segment inflammation (dual fluorescein and ICG angiographic scoring system for uveitis). Int Ophthalmol. 2010 Oct;30(5):539-52. doi: 10.1007/s10792-008-9263-x. Epub 2008 Sep 16.
• Results Ramanan AV, Dick AD, Jones AP, McKay A, Williamson PR, Compeyrot-Lacassagne S, Hardwick B, Hickey H, Hughes D, Woo P, Benton D, Edelsten C, Beresford MW; SYCAMORE Study Group. Adalimumab plus Methotrexate for Uveitis in Juvenile Idiopathic Arthritis. N Engl J Med. 2017 Apr 27;376(17):1637-1646. doi: 10.1056/NEJMoa1614160.
• Song H, Zhao C, Zhang Y, Li D, Qian Y, Gao F, Xiao J, Zhang M. Efficacy and safety of adalimumab for inflammatory flare prevention in paediatric non-infectious anterior uveitis with peripheral retinal vascular leakage: a study protocol for a single-centre, randomised controlled trial. BMJ Open. 2022 Dec 7;12(12):e062211. doi: 10.1136/bmjopen-2022-062211.

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