The goal of this proposal is to develop a clinical trials network capable of engaging in several clinical trials of the treatments of uveitis and its complications. The MUST Research Group (RG) structure already is in place, and processes have been developed for review, approval, and prioritization of clinical trials. Four clinical research studies are proposed as the initial activities of the proposed network, which represent the specific aims of the proposal. These are: 1) To continue the current MUST Trial follow-up past the original two-year determination of the primary outcome for an additional 6 years. This long-term follow-up will enable the MUST RG to evaluate the long-term consequences of the two treatment paradigms: regional corticosteroid treatment v. systemic therapy with corticosteroids and immunosuppression;2) To compare the relative effectiveness of adalimumab (Humira(R), Abbott Laboratories, Abbott Park, IL), a fully human monoclonal antibody to TNF-a v. conventional immunosuppression for patients with severe uveitis requiring immunosuppressive drug therapy. Adalimumab already is approved by the US Food and Drug Administration (FDA) for the treatment of several autoimmune or autoinflammatory diseases, such as rheumatoid arthritis, and preliminary data suggest that it is effective as a corticosteroid-sparing agent in patients with uveitis;3) To compare periocular v. intravitreal corticosteroids for the treatment of macular edema in patients with uveitis. Both periocular and intravitreal corticosteroids appear to be effective for the treatment of macular edema in patients with uveitis, but no comparative trials have been performed. Many clinicians believe that intravitreal corticosteroids are more effective than periocular corticosteroids for this indication, but that they also have higher rates of side effects;and 4) To compare intravitreal ranibizumab (Lucentis(R), Genentech Inc., San Francisco, CA), a monoclonal antibody to vascular endothelial growth factor, to intravitreal corticosteroids for the treatment of refractory macular edema in patients with uveitis. A pilot study suggested that ranibizumab was effective in the treatment of uveitic macular edema and that potentially it may have less ocular side effects than corticosteroids. However, the relative efficacy of the two treatments is unknown.

Public Health Relevance

Non-infectious uveitis is associated with high rates of visual loss and usually requires long-term therapy, often with oral corticosteroids, supplemented, when indicated, by immunosuppressive (corticosteroid- sparing) drugs. Visual loss often is caused by structural complications, e.g., macular edema. We propose to carry out a series of clinical studies to provide an evidence base for the management of these conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
2U10EY014655-06
Application #
8018319
Study Section
Special Emphasis Panel (ZEY1-VSN (11))
Program Officer
Wideroff, Louise
Project Start
2004-07-15
Project End
2017-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
6
Fiscal Year
2012
Total Cost
$336,204
Indirect Cost
$120,102
Name
Icahn School of Medicine at Mount Sinai
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Sugar, Elizabeth A; Holbrook, Janet T et al. (2014) Cost-effectiveness of fluocinolone acetonide implant versus systemic therapy for noninfectious intermediate, posterior, and panuveitis. Ophthalmology 121:1855-62
Drye, Lea T; Casper, Anne S; Sternberg, Alice L et al. (2014) The transitioning from trials to extended follow-up studies. Clin Trials 11:635-47
Hsieh, Jane; Honda, Andrea F; Suarez-Farinas, Mayte et al. (2013) Fundus image diagnostic agreement in uveitis utilizing free and open source software. Can J Ophthalmol 48:227-34
Friedman, David S; Holbrook, Janet T; Ansari, Husam et al. (2013) Risk of elevated intraocular pressure and glaucoma in patients with uveitis: results of the multicenter uveitis steroid treatment trial. Ophthalmology 120:1571-9
Kempen, John H; Sugar, Elizabeth A; Jaffe, Glenn J et al. (2013) Fluorescein angiography versus optical coherence tomography for diagnosis of uveitic macular edema. Ophthalmology 120:1852-9
Sen, H Nida; Drye, Lea T; Goldstein, Debra A et al. (2012) Hypotony in patients with uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial. Ocul Immunol Inflamm 20:104-12
Taylor, Simon R J; Lightman, Susan L; Sugar, Elizabeth A et al. (2012) The impact of macular edema on visual function in intermediate, posterior, and panuveitis. Ocul Immunol Inflamm 20:171-81
Madow, Brian; Galor, Anat; Feuer, William J et al. (2011) Validation of a photographic vitreous haze grading technique for clinical trials in uveitis. Am J Ophthalmol 152:170-176.e1
Kempen, John H (2011) The need for a revised approach to epidemiological monitoring of the prevalence of visual impairment. Ophthalmic Epidemiol 18:99-102
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen, John H; Altaweel, Michael M et al. (2011) Randomized comparison of systemic anti-inflammatory therapy versus fluocinolone acetonide implant for intermediate, posterior, and panuveitis: the multicenter uveitis steroid treatment trial. Ophthalmology 118:1916-26

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