A Comprehensive Review of mTOR-Inhibiting Pharmacotherapy for the Treatment of Non-Infectious Uveitis

作者：Blair Joshua; Barry Robert; Moore David J; Denniston Alastair K^*

来源：Current Pharmaceutical Design, 2017, 23(20): 3005-3014.

DOI：10.2174/1381612823666170111125550

• Uveitis
• mTOR inhibitors
• mammalian target of rapamycin
• immunosuppression
• Non-infectious uveitis
• corticosteroids

Background: Non-infectious uveitis is a sight-threatening inflammatory disease that often necessitates prolonged use of high-dose corticosteroids, resulting in significant systemic side effects. There is a need for efficacious steroid-sparing immunomodulatory therapy for these patients, and the mTOR inhibitors (sirolimus and everolimus) may be contenders for this role.
Methods: A comprehensive review of preclinical and clinical research on mTOR inhibitors for non-infectious uveitis was performed. Articles were identified by a search of MEDLINE (PubMed/OVID) and EMBASE (OVID) the terms (uveitis OR non-infectious uveitis) AND (mTOR inhibitor OR sirolimus OR everolimus). Assessment of study aims, methods, efficacy outcomes and adverse events was performed.
Results: Seven pre-clinical and nine clinical studies were identified. One study in each group was on everolimus, the rest sirolimus. Preclinical studies have been performed in rabbit, rat, mouse and in-vitro models. Clinical studies range from comparative open-label trials to case reports, with reported clinical efficacy ranging from 40% to 100% depending on endpoint assessed. The overall rate of drug-related adverse events (such as ocular irritation, visual floaters, nausea and vomiting) was 0.640 events per patient-year with sirolimus, and 0.111 events per patient-year with everolimus.
Conclusion: Published evidence suggests that sirolimus and everolimus may be useful in the management of noninfectious uveitis. Both appear to be well tolerated, especially when locally administered. Further high-quality RCTs adopting standardised end-points are required to definitively determine the efficacy of each agent.

• 出版日期2017