The current status of biological treatment for uveitis

ABSTRACT

Introduction

Noninfectious uveitis represents one of the leading causes of blindness in developed Countries, compromising patients’ quality of life and social functioning. The main treatment goals are the control of ocular inflammation, to avert and treat sight-threatening complications, thus preserving and/or restoring visual function.

Areas covered

This manuscript deals with systemic therapy with biologic drugs for noninfectious uveitis. An extensive literature search in the MEDLINE database (via PubMed) has been performed up to June 2020. The major classes of biologic molecules employed in ocular inflammatory diseases have been reviewed, focusing on TNF inhibitors, IL-1, IL-6, IL-17, IL-23 inhibitors, interferons, rituximab, and abatacept efficacy and safety. An overview of most recent developments in the field has been provided as well, with reference to the experience with JAK inhibitors and with biosimilar drugs.

Expert opinion

The development of the concept of targeted therapy and the subsequent introduction of biologic molecules in clinical practice have revolutionized the prognosis of uveitis. The target of a rapid and sustained steroid-free remission of ocular inflammation should be pursued for all patients early in the disease course, in order to have a better chance to improve the final visual outcome.

KEYWORDS:

• Abatacept
• biosimilar drugs
• biotechnological therapy
• immunosuppressive treatment
• interferon
• interleukin-1 inhibitors
• interleukin-6 inhibitors
• JAK-inhibitors
• noninfectious uveitis
• rituximab
• steroid-sparing agents
• tumor necrosis factor inhibitors
• uveitis biologic modifier agents

Article highlights

• Uveitis represents one of the main causes of blindness in western Countries, counting for about 15% of preventable loss of vision.

• Both immune and inflammatory dysregulation have been advocated as the driving mechanism leading to tissue damage.

• The target of a rapid and sustained steroid-free remission should be set and adequately pursued for all patients as early as possible during the course of the disease, in order to have a better chance to improve the final visual outcome.

• A multidisciplinary approach to the patient is warranted, especially when uveitis occurs in the context of a systemic disease.

• To date, only adalimumab has obtained EMA and FDA authorization for the treatment of uveitis, while other biologic drugs are employed off-label.

• The use of adalimumab, infliximab and interferon-α 2a is recommended after the failure of conventional DMARDs by the Fundamentals Of Care for UveitiS (FOCUS) Initiative; the American Academy of Ophthalmology strongly recommends infliximab and adalimumab as first- or second-line glucocorticoid-sparing therapy for patients with BD-related uveitis.

• Further agents, including golimumab, certolizumab pegol, rituximab, anakinra, canakinumab, tocilizumab, and sarilumab, should be taken into account when switching nonresponder patients to second- or third-line biologic therapies.

• Less favorable results have been achieved with etanercept, abatacept, IL-17, and IL-23 inhibitors.

• Interfering with JAK/STAT intracellular pathway through JAK inhibitor small molecules is thought to be a promising therapeutic strategy.

• Observational studies suggest that biosimilar molecules are a safe and effective therapeutic option for the treatment of uveitis.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.