Janus Kinase Inhibitors as a Third-Line Therapy for Refractory Endogenous Noninfectious Uveitis

ABSTRACT

Purpose

Janus kinase (JAK) inhibitors have recently been used to treat patients with biologic refractory noninfectious uveitis (NIU). This narrative review updates the current evidence relevant for their application in patients with refractory NIU.

Methods

A literature search was performed for articles published until October 2023 in the PubMed, Scopus, and CENTRAL databases using the key terms “noninfectious uveitis” and “Janus kinase inhibitor” or “JAK inhibitor” without any exclusion criteria. Published articles were selected based on their clinical focus, relevance for ocular disease, time since publication and study design reflecting their scientific soundness with a critical appraisal of drug safety aspects.

Results

Janus kinases are transmembrane signaling proteins. Their inhibition has shown therapeutic potential experimentally and in patients with multiple immune-mediated diseases, including NIU. JAK inhibitors differ from biological agents in that they inhibit not one specific but multiple cytokines. These agents can be ingested orally and seem superior to adalimumab for most indications. While there is no doubt regarding their efficacy in treating immune-mediated inflammatory diseases, reports regarding their safety are increasing, and the findings are generally confusing and contradictory. Since substantiated information about their specific safety profiles in patients with inflammatory eye disease is lacking, their position in the therapeutic algorithm for uveitis has yet to be determined.

Conclusions

In the absence of evidence from controlled clinical trials, JAK inhibitor therapy is still rendered experimental and currently considered only for sight-threatening uveitis. JAK inhibitors may be considered for specific NIU entities for which there is insufficient response or secondary loss of response to conventional or biologic disease-modifying drugs.

KEYWORDS:

• Janus kinase inhibitor
• noninfectious uveitis
• safety
• small molecules
• TNF-α inhibitor

Disclosure statement

The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. JGG has received consultation fees/participation in international multicenter studies and from the company-sponsored speaker bureau of AbbVie, Bayer, Novartis, and Roche.

Précis

While there is no doubt about the efficacy of JAK inhibitors in the treatment of refractory uveitis, their safety profile in treating this disease has remained uncertain. Outside clinical studies, their use should therefore remain limited to third-line therapy for uveitis insufficiently responsive to classical and biological immunomodulation.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.