Abstract
Purpose :
Retinal vasculopathy with cerebral leukoencephalopathy (RVCL) is a rare familial condition that affects the eye and brain microvasculature. RVCL commonly starts in the 30-40s and progresses to blindness, dementia, and premature death around the age of 50 and currently has no approved therapies. The retina demonstrates significant vascular dropout likely due to microvascular occlusive disease. Crizanlizumab is a monoclonal P-selectin antibody used in sickle cell patients that limits microvascular occlusion by preventing leukocyte endothelium adhesion, suggesting a possible therapeutic effect in RVCL. This phase 2 study evaluated the safety and efficacy of crizanlizumab to slow progression of vasculopathy-induced retinal nonperfusion.
Methods :
A total of 10 RVCL patients (n=20 eyes) were included in this 2-year phase 2 analysis of crizanlizumab. Patients aged 38-59 years received infusions of crizanlizumab monthly (5 mg/kg, IV). Fluorescein angiography images at baseline, year 1, and year 2 were segmented according to retinal zones of the posterior pole (<10 mm), midperiphery (10-15 mm) and far periphery (15 mm) and nonperfusion areas were quantified using an Optos proprietary tool. A mixed model analysis accounting for repeated measures and inter-eye correlation was performed.
Results :
No patients experienced severe adverse events, with mild to moderate events attributed to constitutional symptoms (48%) or gastrointestinal symptoms (35%). RVCL patient eyes had an average total nonperfusion of 19.0%, 26.2%, and 25.6% at baseline, year 1, and year 2 respectively (p<.001 comparing each year to baseline). The rate of progression of total nonperfusion was 7.22 [4.47, 9.97] % per year and –0.69 [–4.06, 2.68] % per year during years 1 and 2 respectively (p<.001). Midperiphery nonperfusion showed similar a trend as RVCL patient eyes showed an average nonperfusion of 21.7%, 32.2%, 32.9% at baseline, year 1, and year 2 respectively (p<.001 comparing each year to baseline). The rate of progression of midperiphery nonperfusion was 10.6 [5.1, 16.1] % per year and –0.68 [–3.98, 5.35] % per year during years 1 and 2 respectively (p<.01).
Conclusions :
Crizanlizumab has an acceptable safety profile. This study offers promising potential for studying classes of pharmacologic agents like crizanlizumab in future, larger studies for RVCL and similar small vessel diseases.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.