Session Title: Vascular Diseases I
Session Date/Time: Friday 27/09/2013 | 08:00-10:00
Paper Time: 08:24
Venue: Hall C (Level 1)
First Author: J.Korobelnik FRANCE
Co Author(s): S. Francom P. Lai D. Reshef L. Tuomi
Intravitreal ranibizumab is widely used to treat wet age-related macular degeneration (AMD), diabetic macular edema (DME) and retinal vein occlusion (RVO) with cumulative patient exposure exceeding 1.6 million treatment-years since 2006. Various clinical trials have demonstrated efficacy and safety of ranibizumab in these patients. However, these trials were not powered to assess relative incidences of infrequent adverse events. The purpose of this meta-analysis is to better characterize the safety profiles of 0.3 mg and 0.5 mg ranibizumab using a database containing Genentech and Novartis Phase II, III and IIIb clinical trials.
Phase II, III and IIIb clinical trials on ranibizumab sponsored by Genentech and Novartis.
All available adverse event (AE) information on individual patients from the time of study enrolment until their final follow-up visit was included. The pooled safety database incorporated patient-level data on drug exposure, demographics, key baseline risk factors/ medications and timing of the events relative to study enrolment. Fifteen systemic endpoints were evaluated for each indication (AMD, DME and RVO). The systemic endpoints evaluated were: arterial thromboembolic events, cerebrovascular events, stroke, myocardial infarctions, congestive heart failure, death, fistulae, gastrointestinal perforation, central nervous system (CNS) hemorrhage, non-CNS hemorrhage, hypersensitivity, hypertension, proteinuria, venous thromboembolic events and wound healing complications. Descriptive statistics were calculated to describe safety and to detect trends and safety signals over time.
Fourteen studies qualified for inclusion in this meta-analysis of pair-wise treatment comparisons (studies included both treatment arms being compared). Data from 6504 patients (AMD: 63%, DME: 25%, RVO: 12% patients) with a cumulative 7544 patient years of follow-up from 8 Genentech and 6 Novartis studies were included. In the AMD and RVO patients, no imbalances were observed for any of the pre-specified systemic endpoints. In DME patients, the majority of the pre-specified endpoints did not show an imbalance. Numerically higher rates were observed in the pairwise comparisons for 0.5 mg versus control (sham/laser) for the following systemic endpoints: death, stroke, and wound healing complications. Numerically higher rates were also observed for 0.3 mg versus control (sham/laser) for the systemic endpoint of death. The numerically higher rates for death and stroke were observed in the second year of treatment where the data consisted of RISE and RIDE patients receiving monthly treatment. Overall, the events rates were low for all groups and consistent with the known safety profile of ranibizumab.
This meta-analysis represents the largest comprehensive evaluation of ranibizumab safety data to date. Past medical history should be considered when assessing individual risks for systemic adverse events. This meta-analysis indicates a safety profile consistent with the previously reported safety profile of ranibizumab from individual randomized, controlled clinical trials.