What are the recent developments in uveitis (inflammation of the uvea)?

From the Guidelines

Recent advances in uveitis include the approval of adalimumab (Humira) as the first FDA-approved biologic for non-infectious uveitis, typically administered as 40mg subcutaneously every other week, as recommended by the 2019 American College of Rheumatology/American Academy of Ophthalmology guidelines 1.

Key Developments in Uveitis Treatment

• Local steroid implants like the fluocinolone acetonide implant (Retisert) and dexamethasone implant (Ozurdex) now provide sustained drug delivery for up to 30 months and 3-6 months respectively, reducing the need for systemic steroids.
• Diagnostic techniques have improved with enhanced OCT imaging, allowing better visualization of inflammatory changes and choroidal thickness.
• The JAK inhibitor tofacitinib has shown promise in treating refractory uveitis cases at doses of 5-10mg twice daily.
• Treatment approaches are becoming more personalized, with earlier introduction of steroid-sparing immunomodulatory therapy to prevent complications.
• Researchers have identified new biomarkers like IL-6 and IL-17 that may help predict disease course and treatment response, as noted in the Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans for juvenile idiopathic arthritis-associated and idiopathic chronic anterior uveitis 1.

Recommendations for Uveitis Management

• The American College of Rheumatology (ACR) and the Arthritis Foundation (AF) recommend regular ophthalmology screening of children with JIA due to the risk of uveitis, with frequency based on individual risk factors 1.
• Initial treatment of children with JIA-associated uveitis typically includes topical glucocorticoids, with methotrexate and tumor necrosis factor inhibitor (TNFi) biologics, such as adalimumab and infliximab, recommended for systemic treatment 1.
• The SHARE initiative provides consensus-based recommendations for the management of uveitis associated with juvenile idiopathic arthritis, including the use of anti-TNF treatment strategies and the potential options of tocilizumab, rituximab, and abatacept for cases refractory to previous anti-TNF therapy 1.

From the FDA Drug Label

In both studies, subjects received placebo or HUMIRA at an initial dose of 80 mg followed by 40 mg every other week starting one week after the initial dose. The primary efficacy endpoint in both studies was ´time to treatment failure´ Treatment failure was a multi-component outcome defined as the development of new inflammatory chorioretinal and/or inflammatory retinal vascular lesions, an increase in anterior chamber (AC) cell grade or vitreous haze (VH) grade or a decrease in best corrected visual acuity (BCVA) Clinical Response Results from both studies demonstrated statistically significant reduction of the risk of treatment failure in patients treated with HUMIRA versus patients receiving placebo. The safety and efficacy of HUMIRA were assessed in adult patients with non-infectious intermediate, posterior and panuveitis excluding patients with isolated anterior uveitis, in two randomized, double-masked, placebo-controlled studies (UV I and II)

The new development in uveitis is the use of HUMIRA (adalimumab), which has been shown to significantly reduce the risk of treatment failure in patients with non-infectious intermediate, posterior, and panuveitis.

• Key findings include:
  • A statistically significant reduction in the risk of treatment failure in patients treated with HUMIRA versus placebo.
  • HUMIRA decreased the risk of treatment failure by reducing the development of new inflammatory lesions, increasing anterior chamber cell grade or vitreous haze grade, or decreasing best corrected visual acuity.
  • The safety and efficacy of HUMIRA were assessed in two randomized, double-masked, placebo-controlled studies (UV I and II) 2.

From the Research

Current Treatment Options for Uveitis

• Corticosteroids are the first line of therapy for patients with noninfectious ocular inflammatory disease, including uveitis 3, 4.
• The treatment approach for uveitis depends on the location and severity of the inflammation, with topical corticosteroids used for anterior uveitis and periocular or intravitreal agents used for intermediate or posterior intraocular inflammation 3.
• Noncorticosteroid immunosuppressive agents, such as methotrexate and mycophenolate mofetil, play an important role in limiting the toxic effects of long-term corticosteroid use 3, 5.

Comparison of Treatment Options

• A randomized clinical trial compared the effect of methotrexate and mycophenolate mofetil on inflammation in patients with uveitis, and found that treatment success occurred in 66.7% of patients in the methotrexate group vs 57.1% in the mycophenolate group 5.
• The study suggested that methotrexate may be more effective than mycophenolate mofetil in achieving corticosteroid-sparing control of noninfectious posterior uveitis or panuveitis, but further research is needed to confirm this finding 5.

Evidence-Based Treatment Guidelines

• A review of evidence-based treatments for non-infectious uveitis highlighted the importance of a prompt diagnosis and assessment of an appropriate treatment, with a stepladder approach starting with the least aggressive treatments to induce remission of inflammation 6.
• The review noted that biologic response modifier treatment options, such as adalimumab, have been shown to be effective in adults and children with non-infectious uveitis 6.
• Another review emphasized the need for a stepladder approach to treatment, with corticosteroids used to treat acute flares and steroid-free remission achieved with the use of chemotherapeutic agents 7.