Focus on Dry Eye

Restasis: 10 years after launch

The drug has found a strong niche in dry eye therapy.

By Jerry Helzner, Senior Editor

Launched by Allergan in the United States in April 2003, Restasis (cyclosporine ophthalmic emulsion 0.05%) had the advantage of being the first — and still the only — FDA-approved prescription drug for chronic dry eye disease. For people who had spent years trying to cope with their disease, primarily with oceans of artificial tears, just two drops of Restasis each day was designed to attack the underlying inflammatory characteristic of the disease and allow patients to produce more natural tears.

Sales continue strong growth

Now, a decade after it was introduced, Restasis can be deemed a success. Ophthalmologists interviewed for this article say it has earned a significant place in their overall treatment plan for combating dry eye disease. Patients worldwide have now accounted for 16 million prescriptions for the drug, translating to a compounded 40% annual sales growth, according to Allergan. In 2004, its first full year of US sales, Restasis totaled $98 million in revenues. This year, Allergan expects Restasis to record between $870 and $900 million in worldwide sales, making it the company’s best-selling ophthalmic drug by far.

In the latest reported quarter, the second quarter 2013, Restasis was still growing sales by double-digits (10.5%), even though the drug has been in the marketplace for a decade. What’s more, Restasis has been blessed with an ongoing marketing campaign featuring a series of television ads that focus on the endorsement of cornea specialist Alison Tendler, MD, of Vance Thompson Vision in Sioux Falls, S.D.

Given that Restasis has made a considerable impact on the treatment of dry eye disease over the past 10 years, what have ophthalmologists who treat dry eye learned about the drug during this time that allows them to use it more effectively? This article will focus on the experiences of three corneal specialists who have successfully integrated Restasis into their arsenal of dry eye treatments, two of whom actually use Restasis themselves.

A scene from one of a series of Restasis television ads featuring spokesperson Alison Tendler, MD.

THE LEARNING CURVE
Restasis needs time to work

Stephen Pflugfelder, MD, of the Cullen Eye Institute at Baylor College of Medicine in Houston, has extensive experience with Restasis, having served as an investigator in the drug’s pivotal phase 3 trial. He believes Restasis came along at just the right time. “In terms of treating dry eye and ocular surface disease, prior to the introduction of Restasis, artificial tears just weren’t cutting it because inflammation is a big part of the disease,” he says. “Restasis has helped us to treat the inflammation.”

Dr. Pflugfelder says he went through a learning curve in the use of Restasis that has helped him to be more accurate in selecting patients for whom the drug is most effective. “First, it’s very important for both doctors and patients to recognize that it takes a while for Restasis to begin to work,” he notes. “It could be four to six weeks and it could even be longer, but I have found that the drug’s effectiveness gets better with time. It is so safe that you can use it indefinitely, which is a major advantage.”

Dr. Pflugfelder says patients who produce low tear volume at baseline tend to do better on Restasis than patients who produce more of their own tears. He has also conducted in-house research that points to patients with low goblet cells as good responders to Restasis therapy. “Restasis appears to have the ability to repair goblet cells,” he notes.

Short-course steroids can help

Because Restasis takes a while to begin to work, Dr. Pflugfelder often starts his dry eye patients with a short course of topical steroids, which lasts about a month. “The topical steroid does two things,” he says. “It provides earlier relief for the patient and it mitigates the burning or stinging sensation that many patients feel when they begin Restasis.”

TREATMENT PLANS AND TIPS
Dr. Pflugfelder’s treatment plan

The cornea specialists interviewed for this article agree that Restasis must be part of an overall treatment plan. It is not a panacea that can stand on its own. “No single drug can work for all patients,” says Dr. Pflugfelder. “An overall treatment plan for dry eye disease could include one or more of the following: supplements such as fish oil, the antibiotic anti-inflammatory doxycycline, punctal plugs and the antibiotic AzaSite (azithromycin, InSite Vision, Alameda. Calif.).”

About 80% of the patients to whom he prescribes the drug do well on it, Dr. Pflugfelder says. “I have patients who have gone from debilitating dry eye to functioning very well. Another benefit is that these patients can decrease the use of artificial tears.”

The doctor is also a patient

Christopher Starr, MD, FACS, of New York-Presbyterian Hospital, Weill Cornell Medical Center in New York, was just completing his fellowship training when Restasis was launched in the United States a decade ago. “I have had the benefit of being able to prescribe Restasis for my entire career,” he notes. “I consider it the foundation of my dry eye treatment plan.”

Dr. Starr also has dry eyes and uses the drug himself with good effect. “I keep it in my medicine cabinet, right near my toothbrush, because that way I’m sure to use it,” he laughs.

Unlike Dr. Pflugfelder, who recommends patients refrigerate Restasis to reduce any stinging sensation from instilling the drug, Dr. Starr has never found the need to refrigerate it himself because he feels the drop is comfortable upon instillation.

Dr. Starr’s treatment plan

“I liked Restasis from the beginning and I have increased my prescribing of it over the years as I’ve gained more experience and witnessed its impressive results,” says Dr. Starr. The definition of dry eye disease has changed as knowledge of the disease continues to grow, he notes. “The most recent definition of dry eye disease from the Dry Eye WorkShop (DEWS) report notes hyperosmolarity and inflammation as key pathophysiologic factors, which supports the use of anti-inflammatory medication such as Restasis.”

Dr. Starr agrees that treating dry eye disease requires an overall treatment plan tailored to each patient because dry eye is a multi-factorial disease. “I start most patients with early moderate and higher disease severity on Restasis because those patients are more likely to have significant ocular surface inflammation,” he says. “A short course of the topical steroid Lotemax (lotoprednol, Bausch + Lomb, Tampa) with Restasis can be used to jump start the reduction of inflammation and help ease the mild burning associated with the initiation of Restasis.”

Treating hyperosmolarity

Dr. Starr prescribes Restasis for most patients with significant hyperosmolarity as diagnosed by the TearLab device (TearLab Corporation, San Diego). Other elements of his dry eye treatment regimen can include AzaSite, which he finds helpful in treating anterior and posterior blepharitis off-label, omega-3 fatty acid supplementation, an emphasis on lid hygiene, warm compresses and lid massage, adjunctive use of artificial tears for symptom control and punctal plugs, among other treatments.

“We consider a decrease in the use of artificial tears a metric of success in treating this disease,” Dr. Starr says. “A significant reduction in artificial tear use was seen in the pivotal clinical trials for Restasis.”

Dr. Starr finds that educating patients in the proper use of Restasis is one of the primary keys to success with the drug. “First, patients must understand that Restasis is not an artificial tear and should not be used ‘as needed,’” he says. “They should use one drop in the morning and one drop in the evening, no more and no less. They should expect some mild burning or stinging at first but a short-course of topical steroid and time will lessen this.”

Dr. Starr says that some patients need as much as three to six months to obtain the full benefits of Restasis. This needs to be explained up front to maintain patient compliance through this initial period.

Dr. Yeu’s treatment plan

Elizabeth Yeu, MD, of Virginia Eye Consultants in Norfolk, is another cornea specialist who both prescribes Restasis and uses it for her own dry eye condition. “I truly believe in the product for early-to-moderate dry eye,” she says. “It does not work that well in the more severe case, stages three and four.”

Dr. Yeu postpones using Restasis in patients who already have a burning sensation in their eyes. “First, we want to calm the eye down with a topical steroid before starting Restasis,” she says. “If they have a foreign-body sensation or blurred vision but no burning we can start Restasis right away.”

“Dr. Yeu says she postpones using Restasis in patients who already have a burning sensation in their eyes”

Episcleritis and lid inflammation

Dr. Yeu also likes to use Restasis for episcleritis, characterized by redness and inflammation. “With dry eye, you must customize the treatment for each patient,” she says. “Younger patients tend to have more symptoms and few signs. For them, Restasis can be very helpful along with omega-3s. Older patients can be just the opposite, with strong signs and few symptoms. They don’t seem to have the discomfort we see in younger patients. That could be because they have been on a number of medications and their senses have become a bit dulled over the years. But they do very well with Restasis, especially if they have a good tear film.”

Dr. Yeu also treats inflamed lids as she wants to stop lid inflammation from spilling over onto and affecting the ocular surface. “I find that about 80% of my dry eye patients do very well on Restasis and just about all patients get some level of relief,” she observes. “Patients who come off Restasis, for whatever reason, almost always get worse. Though they may not have seen improvement from the Restasis when they were using it, it was at least keeping the disease from getting worse. Restasis itself can only do so much, especially with patients who are dealing with other health factors that limit the effectiveness of the Restasis.” OM