Small molecules as therapy for uveitis: a selected perspective of new and developing agents

ABSTRACT

Introduction: Intraocular inflammation (uveitis) remains a significant burden of legal blindness. Because of its immune mediated and chronic recurrent nature, common therapy includes corticosteroids, disease-modifying anti-rheumatic drugs and more recently biologics as immune modulatory agents. The purpose of this article is to identify the role of new treatment approaches focusing on small molecules as therapeutic option in uveitis.

Areas covered: A MEDLINE database search was conducted through February 2017 using the terms ‘uveitis’ and ‘small molecule’. To provide ongoing and future perspectives in treatment options, also clinical trials as registered at ClinicalTrials.gov were included. Both, results from experimental as well as clinical research in this field were included. Since this field is rapidly evolving, a selection of promising agents had to be made.

Expert opinion: Small molecules may interfere at different steps of the inflammatory cascade and appear as an interesting option in the treatment algorithm of uveitis. Because of their highly targeted molecular effects and their favorable bioavailability with the potential of topical application small molecules hold great promise. Nevertheless, a careful evaluation of these agents has to be made, since current experience is almost exclusively based on experimental uveitis models and few registered trials.

KEYWORDS:

• Adhesion molecules
• aldose reductase inhibitor
• alpha 4 integrin inhibitor
• dihydroorotate dehydrogenase inhibitor
• mTOR inhibitor
• phosphodiesterase inhibitor
• small molecule
• sphingosine-1 phosphate receptor 1 antagonist
• JAK/STAT inhibitor
• uveitis

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Article highlights

• Uveitis is an umbrella term that encompasses inflammation of the uvea and retina.

• It accounts for ~ 10–15% of preventable blindness in the Europe/US and can be idiopathic, infectious or associated with systemic disorders.

• Uveitis remains a treatment challenge, since only few agents are currently approved by regulatory agencies (EMA, FDA). Depending on the major site of inflammation (anterior vs. posterior segment) topical, local or systemic application of medication can be considered.

• Current standard of care includes steroids, disease-modifying anti-rheumatic drugs (DMARDs) and more recently biologics (bDMARDs) that are often used in a ‘step ladder’ fashion.

• Recently, ‘small molecules’ became a focus of interest as alternative treatment option. Because of their highly targeted molecular effects and their favorable bioavailability they appear as an interesting option in the treatment algorithm of uveitis and hold great promise.

This box summarizes key points contained in the article.

Declaration of interest

U Pleyer has served as principal investigator or consultant for: Abbvie, Alcon, Allergan, Dompé, Novartis, Santen, Shire and Thea. E Feist has served as principal investigator or consultant for Abbvie, Celgene, Lilly, Pfizer and Bayer. R Kreutz has received honoraria for consulting or research grants from Bayer Pharma, Berlin-Chemie Menarini, Bristol-Myers Squibb, Daiichi Sankyo, Lundbeck, Sanofi and Servier. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Additional information

Funding

This paper was not funded.