Abstract
Purpose: The efficacy and safety profile of ranibizumab is well described based on randomized controlled trials involving >10,000 patients across five indications. However, real-world long term safety and effectiveness have not been widely documented in large populations across diverse regions. The LUMINOUS study (NCT01318941) is designed to assess the long-term safety, effectiveness, treatment-patterns and health-related quality of life associated with ranibizumab treatment in a real-world setting. Here, we present data from the wet age-related macular degeneration (wAMD) cohort from the planned first year interim analyses of the LUMINOUS study Setting: LUMINOUS is an ongoing observational, non-interventional, open-label, multicenter study currently conducted in over 30 countries. Patients treated with ranibizumab for any approved indication in the local product label are recruited Methods: The LUMINOUS study aims to enrol 30,000 patients from 600 sites in 41 countries. Consenting adult patients (treatment naïve or previously treated with ranibizumab or other ocular treatment) were enrolled. Exclusion criteria were simultaneous participation in another investigational study, or systemic/ocular vascular endothelial growth factor (VEGF) inhibitor administration other than ranibizumab in the 90 days prior to study enrolment. Of the 2163 patients recruited up to March 2012, 97.7% had wAMD, 1.7% had diabetic macular edema and 0.6% had retinal vein occlusion. Here, we present the one-year follow up data from the wAMD cohort. In this wAMD cohort (n=2112), 275 (13.0%) were treatment naive (T1), 1829 (86.6%) had previous ranibizumab treatment (T2) and eight (0.4%) had previously received other ocular treatments (T3). Pre-treatment status was defined by the primary-treated eye Results: At baseline, mean age was 79.2 years, 61.8% were female, and 93.7% were Caucasian. The baseline mean visual acuity (VA, ETDRS letter score) was 52.4 and 60.3 for T1 and T2, respectively. The median time from diagnosis to first treatment was 0.04 years (2 weeks) for T1 and the median time from diagnosis to study entry was 1.70 years for T2. Pre-treatment with ranibizumab (T2) was associated with higher VA (60.3/52.4 letters) and lower central retinal thickness (CRT; 255.0/339.7µm) at baseline than the treatment naïve group (T1). At 12 months, patients in T1 gained 4.1 letters, whilst T2 patients generally maintained their higher level of baseline VA (-1.1 letters). Both T1 and T2 groups received 5.2 injections (mean) over 7.4 and 7.5 visits, respectively. At one year, ocular serious adverse events (SAE) for T1 and T2 were 1.1% and 0.4%; non-ocular SAEs were 4.73% and 8.26%, respectively. Overall, the rates of endophthalmitis (T1: 0.36%; T2: 0.11%), cerebrovascular accident (T1: 0.36%; T2: 0.22%) and myocardial infarction (T1: 0%; T2: 0.66%) were low. None of the 36 deaths (1.7%) were deemed study drug/injection procedure related Conclusions: The first year real world outcomes from the LUMINOUS study reinforce the well-established safety and efficacy profile of ranibizumab in wAMD. LUMINOUS includes patients with more diverse demographics than in the pivotal trials and is therefore more representative of real-world patients. Pre-treatment with ranibizumab was associated with higher baseline VA and lower CRT at baseline than the treatment naïve group. wAMD patients achieved good visual acuity outcome at 12 months, irrespective of pre-treatment status, with relatively low numbers of monitoring visits and injections. LUMINOUS will provide an invaluable source of long term real world data on use of ranibizumab therapy