Paul Hahn1, Mina M Chung, Harry W Flynn, Suber S Huang, Judy E Kim, Tamer H Mahmoud, Srinivas R Sadda, Pravin U Dugel. 1. *Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina; †Department of Ophthalmology, University of Rochester Medical Center, Rochester, New York; ‡Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miami, Florida; §Department of Ophthalmology and Visual Sciences, Case Western Reserve University, Cleveland, Ohio; ¶Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin; **Department of Ophthalmology, University of Southern California, Los Angeles, California; and ††Retinal Consultants of Arizona, Phoenix, Arizona.
Abstract
PURPOSE: After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. METHODS: Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. RESULTS: Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. CONCLUSION: Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.
PURPOSE: After the recent approval of ocriplasmin by the Food and Drug Administration, postmarketing safety concerns have been raised by the vitreoretinal community. The American Society of Retina Specialists Therapeutic Surveillance Committee was commissioned to monitor postmarketing drug-related and device-related adverse events. The purpose of this report is to analyze the postmarketing safety experience in the context of available premarketing safety data. METHODS: Periodic aggregate safety reports consisting of premarketing, or clinical trial, data (n = 999 injections) and postmarketing reports through July 16, 2013 (n = 4,387 injections), were retrospectively analyzed by the TSC. The aggregate data were analyzed to classify adverse events, and the postmarketing safety data for each event type were compared with the premarketing data. RESULTS: Eight categories of adverse events were identified. Acute reduction in visual acuity attributable to either worsening of macular pathology or development of subretinal fluid, electroretinogram changes, dyschromatopsia, retinal tears and detachments, lens subluxation or phacodonesis, impaired pupillary reflex, and retinal vessel findings were reported in both the premarketing and postmarketing experiences. Ellipsoid zone (inner segment/outer segment) findings were only reported in the postmarketing experience. Rates of postmarketing reports were lower than in the premarketing data. Adverse events were generally transient, and characteristics of these adverse events were generally similar between the premarketing and postmarketing experience. CONCLUSION: Postmarket analyses are limited by significant underreporting, and in the case of ocriplasmin as a first in-class drug, they may not have captured safety events that have only more recently been identified. Nonetheless, postmarket analyses can identify the scope of potential safety events based on real-world experiences. Ocriplasmin administration should be guided by an appropriate and informed risk-benefit discussion with the patient. Ongoing active postmarket surveillance by all practitioners will continue to be critical to better understand this safety profile.