Biography/Disclosures
Biography: Mali is a vitreoretinal surgeon with The Eye Associates, a private multispecialty ophthalmology practice in Sarasota, Fla.
December 06, 2018
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BLOG: Top five things to know about an innovative drug delivery system for DME

Biography/Disclosures
Biography: Mali is a vitreoretinal surgeon with The Eye Associates, a private multispecialty ophthalmology practice in Sarasota, Fla.
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Standard therapy for the rising number of patients with diabetic macular edema typically consists of anti-VEGF treatments. However, a significant number of patients continue to suffer with persistent DME due to the involvement of pro-inflammatory factors. For these patients, corticosteroids can be a valuable and effective treatment modality.

Therefore, a drug delivery system that provides the continuous therapy these patients require without adding to their treatment burden, such as the one in Iluvien (fluocinolone acetonide, Alimera Sciences), is highly beneficial to optimize patient outcomes. A truly long-term, effective, sustained-release delivery system is a game-changing innovation that offers several advantages over previous options.

A unique delivery system

A drug’s delivery system is an important consideration as it ensures the desired concentration is delivered to the correct target area. Topical drops are notoriously difficult to administer and, even delivered successfully, must still make their way past the anterior segment to where they are needed more posteriorly. Drugs such as triamcinolone can be injected into the correct target area but must be injected frequently to achieve continued efficacy.

Sustained-release medications allow for continuous treatment without the burden of multiple injections. Iluvien’s implant is a non-biodegradable cylindrical polymer tube that measures 3.5 mm in length and 0.37 mm in diameter. The implant containing the fluocinolone acetonide is placed into the vitreous cavity through a 25-gauge needle. The drug then diffuses through the tube, delivering a consistent, sustained release of fluocinolone acetonide for up to 3 years. Unlike other sustained-release options that dissolve after a few months, Iluvien provides long-term, continuous microdosing that has a proven track record of safety and efficacy.

The right drug

There are several commonly used ocular steroids that are all slightly different in chemical composition and efficacy levels. In addition to delivery method, they can also be differentiated by drug penetration. A drug’s water solubility determines how well it will be absorbed by the retinal tissue. A highly water-soluble drug, such as dexamethasone, does not penetrate tissue well and therefore requires higher doses to achieve its efficacy. Fluocinolone acetonide, however, is a synthetic fluorinated corticosteroid with low aqueous solubility, making it lipophilic. This allows it to better penetrate the tissues of the retina, thereby achieving high levels of clinical efficacy from low doses.

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Patient selection

As with most therapies and treatments, patient selection is key in ensuring maximal benefits. The best candidates for Iluvien are patients who respond well to corticosteroids. Carefully screening patients by adhering to the FDA label (previously treated with a course of corticosteroids without a clinically significant rise in IOP) before Iluvien can be completed with a trial of steroids such as topical prednisolone acetate or difluprednate; this will determine if the patient will be likely to have an IOP rise with Iluvien. Additionally, patients who have responded well to a past dexamethasone treatment should do well with Iluvien. This pre-screening will help to mitigate and minimize this potential associated risk. The majority of patients, if properly screened, will do well with sustained-release steroid delivery.

Patient burden and compliance

When patients are not compliant with treatment recommendations, recurrences of DME or significant worsening of diabetic retinopathy are possible. Anti-VEGF therapy is best when used consistently at regular intervals and only extended when the patient demonstrates clinical stability. However, a primary struggle for patients needing anti-VEGF treatments is the burden of frequent injections. With the need for consistent intervals to achieve optimal results, finding the time for frequent appointments can be difficult for many patients.

The benefit of a treatment such as Iluvien is, once the implant is injected into the vitreous, the patient receives continuous microdosing on a daily basis without the need for frequent office visits. It is analogous to a patient maintaining their daily insulin — Iluvien provides the same type of constant management. Therefore, if an appointment is missed, both doctor and patient can be assured that consistent treatment of the DME is maintained.

Safety and consistency

Continuous steroid use may raise the concern of ocular hypertension development or sudden IOP spikes. However, Iluvien has proven to be safe even though it is continuously releasing a microdose of medication. The majority of patients in the clinical trials did not experience rises in IOP, and those who did were adequately controlled with medical therapy. Unlike drugs that require high concentrations in order to be effective, Iluvien reaches its clinical efficacy with such a low concentration that the impact on IOP appears to be minimal.

Whether patients utilize Iluvien as a monotherapy or as a combination therapy with occasional anti-VEGF injections, its sustained-release microdoses offer safe and consistent control over DME. Relieving patients of the burden of frequent appointments and injections while bringing the peace of mind that comes from knowing continuous treatment is occurring is of great benefit to both patient and physician and a much-needed clinical innovation in our field.

 

References:

Campochiaro PA, et al. Ophthalmology. 2010;doi:10.1016/j.ophtha.2009.11.024.

Campochiaro PA, et al. Ophthalmology. 2012;doi:10.1016/j.ophtha.2012.04.030.

Diabetic Retinopathy Clinical Research Network, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1414264.

Dugel PU, et al. Clin Ophthalmol. 2015;doi:10.2147/OPTH.S79948.

Elman MJ, et al. Ophthalmology. 2011;doi:10.1016/j.ophtha.2010.12.033.

Mali J. Choosing the optimal corticosteroid to treat diabetic macular edema (DME) prior to using 0.2 ug/day fluocinolone acetonide implant (FAc; Iluvien). Presented at: American Society of Retina Specialists annual meeting; July 2018; Vancouver, British Columbia.

O’Neil MJ, ed. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 13th ed. 2001:518.

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Romero-Aroca P, et al. J Diabetes Res. 2016;doi:10.1155/2016/2156273.

 

Disclosure: Mali reports he is a consultant, speaker and stock shareholder for Alimera Sciences, a consultant for and recipient of research funding from Allergan, a consultant and speaker for Genentech, a consultant, speaker and stock shareholder for and recipient of research funding from Regeneron, a consultant and speaker for and recipient of research funding from Notal Vision, a consultant and speaker for Sun Pharmaceutical Industries, and a consultant and speaker for Macular Degeneration Association.