Session Title: Vascular Diseases and Diabetic Retinopathy II
Session Date/Time: Friday 18/09/2015 | 16:30-18:00
Paper Time: 17:02
First Author: : M.Larsen DENMARK
Co Author(s): :
CRYSTAL (NCT01535261) was designed to evaluate the long-term efficacy and safety profile of ranibizumab 0.5 mg administered according to the stabilization criteria-driven pro re nata (PRN) dosing regimen (as approved in the European Union) over 24 months in patients with visual impairment due to macular edema secondary to central retinal vein occlusion (CRVO). Here, we present the 24-month efficacy and safety outcomes for the CRYSTAL study.
CRYSTAL was a 24-month, phase IIIb, open-label, single-arm, multi-centre study that enrolled patients with CRVO across 78 sites in Europe, Australia and Canada.
Enrolled patients (N=357) received monthly ranibizumab 0.5 mg intravitreal injections until visual acuity (VA) was stable for three consecutive visits (Phase A). Thereafter, patients were monitored monthly for VA and disease activity, and re-entered Phase A upon signs of deterioration (based on investigators’ assessment). From Month 12, the frequency of monitoring visits could be reduced to every 2 months for patients with stable VA and absence of disease activity. Key objectives of the study were to evaluate the efficacy of an individualized stabilization criteria-driven PRN dosing regimen of ranibizumab 0.5 mg, as assessed by the mean change in best-corrected VA (BCVA) at Month 24 compared with baseline; to evaluate mean change in central subfield thickness [CSFT; assessed by the Central Reading Centre (CRC)] from baseline to Month 24 and to assess the safety profile over 24 months. . Exploratory objectives of the study were to evaluate the influence of baseline BCVA, disease duration and ischemia on BCVA outcomes. Retinal ischemia (assessed by the CRC) was defined as capillary loss (mild, moderate, severe or completely destroyed) in at least one location of the centre, inner or outer subfields, based on the Early Treatment Diabetic Retinopathy Study grid.
Overall, 307 (86.0%) patients completed the 24 month study, and baseline characteristics were generally well-balanced across all treatment groups. At baseline, mean age was 65.5 years, mean (median) duration of CRVO was 8.9 (2.4) months and mean VA was 52.9 letters, with 21.0%, 37.5% and 41.5% of patients having baseline VA of ≤39, 40–59 and ≥60 letters, respectively. Approximately, 25% of patients had disease duration of ≥9 months, and 30.0% had retinal ischemia at baseline, as assessed by the CRC. At Month 24, mean BCVA increased by 12.1 letters, with a mean of 13.1 ranibizumab injections, accompanied by a substantial reduction in mean CSFT (-349.1µm). Mean BCVA gain at Month 24 by baseline VA subgroups (≤39, 40–59 and ≥60 letters) was 18.5, 13.9 and 7.2 letters; by prior duration of CRVO (<3and ≥12 months) was 13.2 and 8.6 letters; and by baseline ischemia status (ischemic and non-ischemic) was 11.1 and 12.9 letters, respectively. Overall, 58.8% and 63.9% of patients were reported with ocular and non-ocular adverse events (AEs) and 2.8% and 15.1% of patients were reported with ocular and non-ocular serious AEs, respectively. The 24-month safety profile was consistent with the established safety profile of ranibizumab.
The findings from the 24-month CRYSTAL study support that patients with CRVO can be effectively managed by individualized ranibizumab dosing regimen, with a mean gain in BCVA of 12.1 letters from baseline to month 24 after PRN dosing with 0.5-mg ranibizumab injections. The subgroup analyses of BCVA across the demographic and baseline characteristics indicate that all subgroups benefit from ranibizumab treatment. Patients with lower baseline VA had higher BCVA gains, while patients with higher baseline VA continued to gain and maintain BCVA over 24 months. Likewise, patients with shorter duration of disease (<3 months) benefited more from ranibizumab treatment than those with longer duration of disease, which suggests that earlier ranibizumab treatment initiation provides substantial VA gains in patients with CRVO. Ranibizumab provided similar BCVA gains, irrespective of the baseline ischemia status, thus further reinforcing its use in patients with CRVO. Overall, the CRYSTAL 24-month data demonstrates the long-term efficacy and safety profile of ranibizumab in CRVO.