The goal ofthis 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 ofthe proposed network, which represent the specific aims ofthe proposal. These are: 1) To continue the current MUST Trial follow-up past the original two-year determination ofthe primary outcome for an additional 6 years. This long-term follow-up will enable the MUST RG to evaluate the long-term consequences ofthe 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 ofthe 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 ofthese conditions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10EY014655-08
Application #
8655154
Study Section
Special Emphasis Panel (ZEY1)
Program Officer
Wideroff, Louise
Project Start
2004-07-15
Project End
2017-04-30
Budget Start
2014-05-01
Budget End
2015-04-30
Support Year
8
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10029
Holbrook, Janet T; Sugar, Elizabeth A; Burke, Alyce E et al. (2016) Dissociations of the Fluocinolone Acetonide Implant: The Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Study. Am J Ophthalmol 164:29-36
Altaweel, Michael M; Gangaputra, Sapna S; Thorne, Jennifer E et al. (2016) Morphological assessment of the retina in uveitis. J Ophthalmic Inflamm Infect 6:33
Sen, H Nida; Abreu, Francis M; Louis, Thomas A et al. (2016) Cataract Surgery Outcomes in Uveitis: The Multicenter Uveitis Steroid Treatment Trial. Ophthalmology 123:183-90
Yu, Tsung; Holbrook, Janet T; Thorne, Jennifer E et al. (2016) Using a patient-centered approach to benefit-harm assessment in treatment decision-making: a case study in uveitis. Pharmacoepidemiol Drug Saf 25:363-71
Yu, Tsung; Holbrook, Janet T; Thorne, Jennifer E et al. (2015) Outcome Preferences in Patients With Noninfectious Uveitis: Results of a Best-Worst Scaling Study. Invest Ophthalmol Vis Sci 56:6864-72
Tomkins-Netzer, Oren; Lightman, Susan; Drye, Lea et al. (2015) Outcome of Treatment of Uveitic Macular Edema: The Multicenter Uveitis Steroid Treatment Trial 2-Year Results. Ophthalmology 122:2351-9
Multicenter Uveitis Steroid Treatment (MUST) Trial Follow-up Study Research Group (2015) Quality of Life and Risks Associated with Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, or Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatmen Ophthalmology 122:1976-86
Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group; Kempen, John H; Altaweel, Michael M et al. (2015) Benefits of Systemic Anti-inflammatory Therapy versus Fluocinolone Acetonide Intraocular Implant for Intermediate Uveitis, Posterior Uveitis, and Panuveitis: Fifty-four-Month Results of the Multicenter Uveitis Steroid Treatment (MUST) Trial and Follow-up Ophthalmology 122:1967-75
Kempen, John H; Van Natta, Mark L; Altaweel, Michael M et al. (2015) Factors Predicting Visual Acuity Outcome in Intermediate, Posterior, and Panuveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial. Am J Ophthalmol 160:1133-1141.e9
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

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