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Ocriplasmin success based on proper patient selection
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Real-world experience with ocriplasmin indicates it is an effective, safe, and cost-effective treatment for symptomatic vitreomacular adhesion in properly selected eyes.
Take-home message: Real-world experience with ocriplasmin indicates it is an effective, safe, and cost-effective treatment for symptomatic vitreomacular adhesion in properly selected eyes.
By Cheryl Guttman Krader; Reviewed by Peter W. Stalmans, MD
Leuven, Belgium - Real-world outcomes with ocriplasmin (Jetrea, ThromboGenics) for the treatment of symptomatic vitreomacular adhesion (VMA) are at least as good as, if not better, than those achieved in pre-marketing clinical trials.
The accumulating clinical experience is also building support for intervention with ocriplasmin in appropriately selected cases, said Peter W. Stalmans, MD.
Providing a perspective on ocriplasmin injection in Europe, Dr. Stalmans noted that the approved indication is for treatment of vitreomacular traction (VMT), including when associated with macular hole of diameter ≤400 µm. Based on the identification of predictors for success in the MIVI-TRUST pivotal trial program, ocriplasmin is most commonly used to treat VMT with or without a macular hole ≤400 µm when the adhesion size is <1,500 µm and there is no epiretinal membrane.
A look at data from five large centers across Europe shows that among eyes without a macular hole, the success rate ranged from 45% to 85%.
“The average success rate among these centers is about 75%, which is more than double the success rate seen in the phase III trials,” said Dr. Stalmans, professor of ophthalmology, University of Leuven, Leuven, Belgium.
Among eyes with a macular hole accompanying VMT, Dr. Stalmans reported that in his hands, the success rate has been 40%. However, it has ranged from 60% to 75% at other centers.
Responding to naysayers
Dr. Stalmans noted that critics of ocriplasmin point to the 26.5% overall success rate achieved in the pivotal trials. However, the data from clinical experience indicate that with selection of appropriate patients, the success rate is much higher.
Another concern has been that use of ocriplasmin will lead to a decline in surgical procedures for vitreoretinal specialists.
“If one chooses ideal patients for ocriplasmin and can achieve success in up to 60% of those cases, there will be 40% fewer of those ideal patients who will undergo surgery,” Dr. Stalmans said.
“However, only about 1.5% of all vitrectomies are performed for tractional disease of the vitreomacular interface,” he said. “That means use of ocriplasmin will have a minimal impact on the number of surgeries performed.”
It has also been suggested that ocriplasmin injection may be overtreatment based on the belief that the majority of VMT cases resolve spontaneously.
Dr. Stalmans noted that a retrospective analysis he conducted showed that among eyes with VMT, only 25% had spontaneous release of traction during the first year of follow-up. while 30% showed progression necessitating vitrectomy.
“Early treatment reduces the likelihood of progressive visual acuity reduction, and that weighs in favor of intervening with ocriplasmin,” he said.
Cost-effective analysis
Clinicians who argue against ocriplasmin also point to its high price, which is about €3,000, or about $4,000 U.S. However, results of health-economic analyses conducted in several European countries show that ocriplasmin is cost-effective when it is used with proper patient selection criteria.
“It should also be considered that unlike anti-vascular endothelial growth factor injections, ocriplasmin is a one-time treatment,” Dr. Stalmans said. “In addition, when evaluating cost-effectiveness, we should not overlook that many patients are treated because of symptoms of metamorphopsia, and resolution of metamorphopsia translates into a gain of 2 lines of best-corrected visual acuity.”
Dr. Stalmans noted that ocriplasmin had an acceptable safety profile in the premarketing trials. Although it was associated with several adverse events, they were transient. In commercial use, no new safety signals have emerged. Furthermore, pharmacokinetics and preclinical safety data should also ease concerns about enzymatic degradation of ocular structures.
“We know that ocriplasmin is completely cleared from the eye within 24 hours of injection,” Dr. Stalmans explained. “Preclinical data show that intraretinal morphology and ultrastructure of the internal limiting membrane are well preserved, and the rate of lens subluxation due to possible digestion of the zonular fibers appears to be just 0.01 per 100 doses, which I think is fairly acceptable.”
He added that no serious systemic safety issues occurred in clinical trials and they are not expected–since any ocriplasmin that enters the peripheral bloodstream would be rapidly deactivated by circulating levels of α2-antiplasmin.
“In other clinical settings, ocriplasmin has been administered intravenously at a dose 1,000-fold higher than the dose used intravitreally and without any severe adverse events,” Dr. Stalmans said.
Peter W. Stalmans, MD, PhD
This article was adapted from Dr. Stalmans’ presentation during the 2014 meeting of the American Academy of Ophthalmology. Dr. Stalmans receives travel fees and grant support from ThromboGenics and is a consultant and receives travel fees from Alcon Laboratories.
