In the POINT trial, intraocular pressure increased by more than 10 mm Hg in 39% of patients receiving intravitreal dexamethasone. In contrast, no sustained intraocular pressure elevations or new cataracts were reported with vamikibart across dose groups in the phase 1 DOVETAIL trial, although the studies were not designed for direct comparison.
In a JAMA Ophthalmology Viewpoint, Stephanie M. Llop, MD, of Bascom Palmer Eye Institute and the University of Miami Miller School of Medicine, and Swati L. Narayan, BA, of Rutgers Robert Wood Johnson Medical School, summarized findings from the phase 1 DOVETAIL nonrandomized clinical trial of vamikibart, an intravitreal anti–interleukin-6 monoclonal antibody, for noninfectious uveitic macular edema.
Corticosteroids remain a standard treatment for uveitic macular edema but are associated with cataract formation, elevated intraocular pressure, and systemic adverse effects with systemic use. DOVETAIL was designed to assess safety and tolerability, not efficacy. Across the three dose levels studied, no drug-related serious adverse events were reported. One patient experienced worsening uveitis, which resolved after 75 days and was considered unrelated to the study drug.
Visual and anatomic outcomes were promising but preliminary. Mean best-corrected visual acuity letter score improvements of 10.7 and 9.0 in the two lower dose groups appeared to be maintained through 36 weeks. Follow-up in the highest-dose group ended at week 20. More than 80% of participants had complete resolution of intraretinal fluid by week 12, maintained in 67% to 90% of participants at study end.
Improvements in anterior chamber cells and vitreous haze suggest that intravitreal interleukin-6 inhibition may affect intraocular inflammation beyond macular edema. The Viewpoint authors noted similar findings with systemic interleukin-6 inhibition, such as tocilizumab, but emphasized that these observations remain preliminary.
“At this time, there are no intravitreal biologic therapies approved for this indication, and current therapies such as corticosteroids and systemic immunosuppressants have limitations,” the authors wrote.
The study’s limitations include its small size, lack of randomization, and absence of a comparison group. Patients with anterior, intermediate, posterior, and panuveitis were included without stratification, which may confound interpretation because treatment response may vary by uveitis subtype. Without a control arm, the observed improvements cannot be distinguished from the natural course of disease.
Two ongoing phase 3 trials, MEERKAT and SANDCAT, are expected to further evaluate the safety and efficacy of vamikibart in patients with uveitic macular edema.
The authors declared having no competing interests.
Source: JAMA Ophthalmology
