Skip to main content
Top
Published in: Journal of Ophthalmic Inflammation and Infection 1/2011

Open Access 01-03-2011 | Original Research

A retrospective review of oral low-dose sirolimus (rapamycin) for the treatment of active uveitis

Authors: Brandon N. Phillips, Keith J. Wroblewski

Published in: Journal of Ophthalmic Inflammation and Infection | Issue 1/2011

Login to get access

Abstract

Purpose

The purpose of this study is to elicit the role of oral low-dose sirolimus as a corticosteriod-sparing agent for active uveitis.

Methods

A retrospective, interventional case series was performed by reviewing the clinical records of all patients treated with oral, low-dose sirolimus (1–4 mg daily) for severe uveitis. Data reviewed included symptomatic improvement, Snellen best-corrected visual acuity, corticosteroid requirement, sirolimus levels, intraocular inflammation, spectral-domain optical coherence tomography, and fluorescein angiogram. Primary outcome measures were determined by the ability to decrease the intraocular inflammation, corticosteroid requirement, and frequency of flares.

Results

Eight patients with varied diagnoses were treated with oral low-dose sirolimus for severe, chronic uveitis between 2008 and 2010. In four of the eight patients, there was an improvement of all primary outcome measures. While sirolimus monotherapy was successful in only one patient, a sirolimus/methotrexate combination was successful in three patients. Although there was a good initial response in three patients, treatment was a failure after serious side effects forced the cessation of sirolimus therapy. One patient was lost to follow-up.

Conclusion

Sirolimus may have a limited role in severe uveitis as an adjunct corticosteroid-sparing agent in combination with more standard immunosuppressive agents. Oral low-dose sirolimus appeared to be better tolerated than higher doses, but there were a significant number of adverse events, requiring therapy to be stopped.
Literature
1.
go back to reference Gritz DC, Wong IG (2004) Incidence and prevalence of uveitis in Northern California: the Northern California epidemiology of uveitis study. Ophthalmology 111(3):491–500PubMedCrossRef Gritz DC, Wong IG (2004) Incidence and prevalence of uveitis in Northern California: the Northern California epidemiology of uveitis study. Ophthalmology 111(3):491–500PubMedCrossRef
2.
go back to reference Buhaescu I, Izzedine H, Covic A (2006) Sirolimus–challenging current perspectives. Ther Drug Monit 28:577–584PubMedCrossRef Buhaescu I, Izzedine H, Covic A (2006) Sirolimus–challenging current perspectives. Ther Drug Monit 28:577–584PubMedCrossRef
3.
go back to reference Sehgal SN (2003) Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc 35(Suppl 3A):7S–14SPubMedCrossRef Sehgal SN (2003) Sirolimus: its discovery, biological properties, and mechanism of action. Transplant Proc 35(Suppl 3A):7S–14SPubMedCrossRef
4.
go back to reference Dutcher JP (2004) Mammalian target of rapamycin inhibition. Clin Cancer Res 10:63282S–66387SCrossRef Dutcher JP (2004) Mammalian target of rapamycin inhibition. Clin Cancer Res 10:63282S–66387SCrossRef
5.
go back to reference Hudes GR, Berkenbilt A, Feingold J, Atkins MB, Rini BI, Dutcher J (2009) Clinical trial experience with temsirolimus in patients with advanced renal cell carcinoma. Semin Oncol 36(Suppl 3):S26–S36PubMedCrossRef Hudes GR, Berkenbilt A, Feingold J, Atkins MB, Rini BI, Dutcher J (2009) Clinical trial experience with temsirolimus in patients with advanced renal cell carcinoma. Semin Oncol 36(Suppl 3):S26–S36PubMedCrossRef
6.
go back to reference Greenhalgh J, Hockenhull J, Rao N, Dundar Y, Dickson RC, Bagust A (2010) Drug-eluting stents versus bare metal stents for angina or acute coronary syndromes. Cochrane Database Syst Rev 5:CD004587PubMed Greenhalgh J, Hockenhull J, Rao N, Dundar Y, Dickson RC, Bagust A (2010) Drug-eluting stents versus bare metal stents for angina or acute coronary syndromes. Cochrane Database Syst Rev 5:CD004587PubMed
7.
go back to reference Mousa SA, Mousa SS (2010) Current status of vascular endothelial growth factor inhibition in age-related macular degeneration. BioDrugs 24(3):183–194PubMedCrossRef Mousa SA, Mousa SS (2010) Current status of vascular endothelial growth factor inhibition in age-related macular degeneration. BioDrugs 24(3):183–194PubMedCrossRef
8.
go back to reference Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of Uveitis Nomenclature (SUN) working group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 140:509–516PubMedCrossRef Jabs DA, Nussenblatt RB, Rosenbaum JT (2005) Standardization of Uveitis Nomenclature (SUN) working group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol 140:509–516PubMedCrossRef
9.
go back to reference Barakat MR, Kaiser PK (2009) VEGF inhibitors for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs 18(5):637–646PubMedCrossRef Barakat MR, Kaiser PK (2009) VEGF inhibitors for the treatment of neovascular age-related macular degeneration. Expert Opin Investig Drugs 18(5):637–646PubMedCrossRef
10.
go back to reference Hudson CC, Liu M, Chiang GG et al (2002) Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol 22:7004–7014PubMedPubMedCentralCrossRef Hudson CC, Liu M, Chiang GG et al (2002) Regulation of hypoxia-inducible factor 1alpha expression and function by the mammalian target of rapamycin. Mol Cell Biol 22:7004–7014PubMedPubMedCentralCrossRef
11.
go back to reference Kleinman DM, Kim DD, Nivaggioli T et al (2007) Sirolimus Inhibits VEGF-Induced Microvascular Hyperpermeability. Invest Ophthalmol Vis Sci 48:1422 Kleinman DM, Kim DD, Nivaggioli T et al (2007) Sirolimus Inhibits VEGF-Induced Microvascular Hyperpermeability. Invest Ophthalmol Vis Sci 48:1422
12.
go back to reference Stahl A, Paschek L, Martin G et al (2008) Rapamycin reduces VEGF expression in retinal pigment epithelium (RPE) and inhibits RPE-induced sprouting angiogenesis in vitro. FEBS Lett 582(20):3097–3102, Epub 2008 Aug 12PubMedCrossRef Stahl A, Paschek L, Martin G et al (2008) Rapamycin reduces VEGF expression in retinal pigment epithelium (RPE) and inhibits RPE-induced sprouting angiogenesis in vitro. FEBS Lett 582(20):3097–3102, Epub 2008 Aug 12PubMedCrossRef
13.
go back to reference Martin DF, DeBarge LR, Nussenblatt RD et al (1995) Synergistic effect of rapamycin and cyclosporin A in the treatment of experimental autoimmune uveoretinitis. J Immunol 154:922–927PubMed Martin DF, DeBarge LR, Nussenblatt RD et al (1995) Synergistic effect of rapamycin and cyclosporin A in the treatment of experimental autoimmune uveoretinitis. J Immunol 154:922–927PubMed
14.
go back to reference Shanmuganathan VA, Casely EM, Powell RJ et al (2005) The efficacy of sirolimus in the treatment of patients with refractory uveitis. Br J Ophthalmol 89:666–669PubMedPubMedCentralCrossRef Shanmuganathan VA, Casely EM, Powell RJ et al (2005) The efficacy of sirolimus in the treatment of patients with refractory uveitis. Br J Ophthalmol 89:666–669PubMedPubMedCentralCrossRef
15.
go back to reference Benavides CA, Pollard VB, Mauiyyedi S, Podder H, Knight R, Kahan BD (2007) BK virus-associated nephropathy in sirolimus-treated renal transplant patients: incidence, course, and clinical outcomes. Transplantation 84(1):83–88PubMedCrossRef Benavides CA, Pollard VB, Mauiyyedi S, Podder H, Knight R, Kahan BD (2007) BK virus-associated nephropathy in sirolimus-treated renal transplant patients: incidence, course, and clinical outcomes. Transplantation 84(1):83–88PubMedCrossRef
16.
go back to reference Douglas LC, Yi NY, Davis JL, Salmon JH, Gilger BC (2008) Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses. J Vet Pharmacol Ther 31(6):511–516PubMedCrossRef Douglas LC, Yi NY, Davis JL, Salmon JH, Gilger BC (2008) Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses. J Vet Pharmacol Ther 31(6):511–516PubMedCrossRef
17.
go back to reference Manzano RP, Peyman GA, Khan P, Kivilcim M, Chevez-Barrios P, Takahashi W (2009) Testing intravitreal toxicity of rapamycin in rabbit eyes. Arq Bras Oftalmol 72(1):18–22PubMedCrossRef Manzano RP, Peyman GA, Khan P, Kivilcim M, Chevez-Barrios P, Takahashi W (2009) Testing intravitreal toxicity of rapamycin in rabbit eyes. Arq Bras Oftalmol 72(1):18–22PubMedCrossRef
Metadata
Title
A retrospective review of oral low-dose sirolimus (rapamycin) for the treatment of active uveitis
Authors
Brandon N. Phillips
Keith J. Wroblewski
Publication date
01-03-2011
Publisher
Springer Berlin Heidelberg
Published in
Journal of Ophthalmic Inflammation and Infection / Issue 1/2011
Electronic ISSN: 1869-5760
DOI
https://doi.org/10.1007/s12348-010-0015-5

Other articles of this Issue 1/2011

Journal of Ophthalmic Inflammation and Infection 1/2011 Go to the issue