Ocular inflammatory diseases are major causes of vision loss in the United States, at a relatively early age. Immunosuppression is a primary therapeutic approach for severe cases. In a, a multicenter retrospective cohort study, we linked 7,957 ocular inflammation patients seen by 2005 inclusive to the National Death Index (NDI), finding 936 deaths over 66,902 person-years of follow-up for mortality. Primary findings included: 1) a suggestion of substantially increased overall and cancer mortality with Tumor Necrosis Factor (TNF) inhibitor therapy;2) no increased risk of overall and cancer mortality with antimetabolite, T-cell inhibitor, or systemic corticosteroid therapy;and 3) overall and cancer mortality risk very similar the general population (suggesting that inflammatory eye diseases patients may be a group in which the indications-for- treatment will not bias study of the relationship between treatment use and mortality or cancer). Millions of individuals in the United States use TNF inhibitors for a range of inflammatory diseases. We propose to extend the study for five years in order to: 1) validate preliminary findings re: overall and cancer mortality risk with TNF inhibitor therapy;2) evaluate cancer incidence (fatal and non-fatal) for all four major classes of immunosuppressive agents;3) generalize statistical methodology accounting for time- dependent confounding to the paired organ setting, to allow more valid analyses of treatment effects using observational ophthalmic data;and, 4) apply these methods to evaluate the relative (cost-) effectiveness of alternative immunosuppressive drugs. We will increase the cohort size by ~35% at the five original centers;the follow-up time and number of deaths observed will nearly double. TNF inhibitor-focused enrollment at ancillary centers will enhance statistical power for aim #1. We will link the enlarged database to the NDI and state cancer registries, with a new co-investigator who successfully completed a similar multiple cancer registry study. A biostatistical methodologist will generalize methods for dealing with time-dependent confounding to the paired organ setting, applying these methods along with a seasoned health economist to directly compare the costs and effectiveness of alternative immunosuppresive drugs for ocular inflammation.
The drugs studied are used by millions;well-powered estimates of their impact on mortality and cancer will affect risk-benefit ratios profoundly, widely influencing management of eye and systemic diseases of immunity. Estimation of the relative (cost-) effectiveness of alternative immunosuppressants for ocular inflammation will greatly increase the quality of evidence available to guide rational clinical management.
|Daniel, Ebenezer; Pistilli, Maxwell; Kothari, Srishti et al. (2017) Risk of Ocular Hypertension in Adults with Noninfectious Uveitis. Ophthalmology 124:1196-1208|
|Kempen, John H; Gewaily, Dina Y; Newcomb, Craig W et al. (2016) Remission of Intermediate Uveitis: Incidence and Predictive Factors. Am J Ophthalmol 164:110-7.e2|
|Patel, Apurva K; Newcomb, Craig W; Liesegang, Teresa L et al. (2016) Risk of Retinal Neovascularization in Cases of Uveitis. Ophthalmology 123:646-54|
|Kothari, Srishti; Foster, C Stephen; Pistilli, Maxwell et al. (2015) The Risk of Intraocular Pressure Elevation in Pediatric Noninfectious Uveitis. Ophthalmology 122:1987-2001|
|Lerman, Melissa A; Lewen, Michael D; Kempen, John H et al. (2015) Uveitis Reactivation in Children Treated With Tumor Necrosis Factor Alpha Inhibitors. Am J Ophthalmol 160:193-200.e1|
|Levin, Marc H; Pistilli, Maxwell; Daniel, Ebenezer et al. (2014) Incidence of visual improvement in uveitis cases with visual impairment caused by macular edema. Ophthalmology 121:588-95.e1|
|Artornsombudh, Pichaporn; Pistilli, Maxwell; Foster, C Stephen et al. (2014) Factors predictive of remission of new-onset anterior uveitis. Ophthalmology 121:778-84|
|Sen, H Nida; Vitale, Susan; Gangaputra, Sapna S et al. (2014) Periocular corticosteroid injections in uveitis: effects and complications. Ophthalmology 121:2275-86|
|Gregory 2nd, Anthony C; Kempen, John H; Daniel, Ebenezer et al. (2013) Risk factors for loss of visual acuity among patients with uveitis associated with juvenile idiopathic arthritis: the Systemic Immunosuppressive Therapy for Eye Diseases Study. Ophthalmology 120:186-92|
|Lerman, Melissa A; Burnham, Jon M; Chang, Peter Y et al. (2013) Response of pediatric uveitis to tumor necrosis factor-? inhibitors. J Rheumatol 40:1394-403|
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