Searching for one therapy to treat all dry eye patients is pointless. This complex, multifactorial disease has forced clinicians to constantly look for new therapies, especially those that are anti-inflammatories as inflammation is often at the root of dry eye disease.
Lifitegrast 5% ophthalmic solution (Xiidra, Shire) is the first FDA-approved medication for the treatment of the signs and symptoms of dry eye disease. It was FDA approved in July 2016, and commercially available shortly thereafter. Lifitegrast was studied in more than 2,000 patients in a series of clinical trials, and has a demonstrated safety profile. In all four studies lifitegrast improved patients’ eye dryness score at six weeks, and in three out of four studies inferior corneal staining score was improved with lifitegrast compared to vehicle at week 12.
Now that we have had lifitegrast in our hands for the past few months, I can say that the clinical trial data mirror my personal experience, and it is nice to have an additional anti-inflammatory agent to treat dry eye.
MAKING IT WORK
I have been using lifitegrast in a variety of patients — those with dry eye disease, pre-surgical patients and those with chronic inflammatory conditions. Lifitegrast is administered twice daily, and is supplied in a preservative-free, disposable, single-use vial. The drug is generally well tolerated, with the most common complaints being dysgeusia (funny taste after instillation), temporary blurred vision and burning/irritation after instillation. In my clinical practice I spend time counseling the patient regarding these potential adverse effects, and I find that if I counsel the patient appropriately his or her medication adherence improves. Most patients are well versed with ophthalmic drugs tasting funny, especially if they have been on steroid eye drops in the past. Because the dysgeusia can occur at any time with lifitegrast, I instruct all my patients to do punctal occlusion after instillation of the drop, as I believe the taste issue may be mitigated if less medication travels into the nasal and oropharyngeal passages. Of the many patients I have treated with lifitegrast, between 5% and 10% have preferred to stop the medication due to this common side effect. Similarly, in my experience up to 10% of patients may discontinue due to burning sensation.
Lifitegrast in the marketplace
According to data from Shire, lifitegrast — or Xiidra — is already cutting a swath in the eye-care Rx marketplace:
- More than 274,386 total prescriptions were written since its August 2016 launch through Jan. 27, 2017.
- Xiidra captured 19% of the total prescription market share as of Dec. 20.
- 65% of Xiidra prescriptions are written for treatment-naive patients.
But, Allergan’s Restasis (cyclosporine) still retains its first-on-the-Rx-scene advantage. The company cites IMS Health’s data showing that 3,298,022 prescriptions of Restasis were generated in 2016.
Patients report a wide variance in severity of symptoms, but thankfully it is much less frequent for a patient to have burning or dysgeusia intense enough to discontinue therapy. In the clinical trial data, patients who experienced burning and dysgeusia reported decreasing symptoms with continued use. Encouraging and supporting patients through the initial reactions will help with patient compliance and confidence in the treatment.
BUT CYCLOSPORINE IS STILL VALUABLE
While lifitegrast is the newest approved molecule for the treatment of dry eye, cyclosporine 0.05% remains an excellent drug for the treatment of inflammation related to dry eye disease. Cyclosporine 0.05% (Restasis, Allergan) has a long history, as it has been available on the market for more than 10 years.
A tale from the dry eye trenches
Johnny Gayton, MD has been a cataract surgeon for 38 years: for half that time, he’s also had dry eye disease.
Not just the itchy, red around the rim dry eye, but the severe kind that can result from epidemic keratoconjunctivitis. The kind that frequently requires steroids, NSAIDs and copious artificial tears.
His TearLab osmolarity test was in the 300s. His LipiView showed three shortened meibomian glands in each lower lid. That was it. His InflammaDry was strongly positive OU.
A particularly low moment was the night he attended an indoor dinner with his peers — wearing wraparound sunglasses.
“[DED] impacted my quality of life for 20 years,” said Dr. Gayton during a break at this year’s Telling It Like It Is conference in Naples, Fl. “It is an incurable disease, and I expect it to do nothing but get worse.”
Well maybe not. On Aug. 1, 2016 lifitegrast (Xiidra, Shire) Dr. Gayton became the first person to use it in middle Georgia. Within two days, his eyes were feeling better. By August 4 he knew his life was going to get a whole lot better.
Up until then, he had tried whatever the dry eye market had to offer, and had some of the best-known dry eye experts treat him.
He isn’t prepared to call lifitegrast a miracle drug, even though it’s impact on him has been remarkable. Many of the people who symptomatically improve the most are those who have the worst cases of DED; he adds that physicians need to educate people on the value of treating asymptomatic disease.
For those who know Johnny Gayton, they know he is sharing his tale with the desire to alleviate the symptoms and improve the quality of life of his dry eye patients. When patients know you are in the trenches with them, he says, “it endears you to them.”
The onset of action of cyclosporine is typically between three and six months — this time difference is a major disparity between it and lifitegrast. In two of the FDA trials, lifitegrast was shown to work by the second week, but it also showed efficacy at six and 12 weeks.
Patients come with different expectations — some are apprehensive about trying something new, while others just want rapid relief. I continue to prescribe cyclosporine for those who tolerate it well and who experience relief of their dry eye symptoms. For those who could not tolerate cyclosporine or those with persistent symptoms despite cyclosporine use, I have also been prescribing lifitegrast, in some cases concomitantly. There are no data so far comparing the two medications. Both work on different aspects of the inflammatory cascade, which may prove to have synergistic effects in some patients.
PATIENTS IN NEED
With increasing use of point-of-care testing, such as osmolarity and MMP-9 testing, I find that I am diagnosing dry eye disease more often than in the past. When you see an elevated MMP-9 level, you know there is inflammation on the surface that must be addressed. The most rapidly growing population for whom I prescribe lifitegrast is those who present for surgical evaluation (ie, for LASIK or refractive cataract surgery) who also have concomitant dry eye disease.
The tear film plays a critical role in vision quality, so not treating dry eye disease prior to surgery means a high likelihood of dissatisfaction postoperatively. Given the potential rapid onset of action, I have prescribed lifitegrast to these surgical patients, as frequently the corneal staining improves faster so patients do not have to delay surgery.
As with any new therapy, cost is a major consideration for patients. To date, many insurance carriers are covering the medication, but often require prior authorization. This process can be onerous in the beginning but in our clinic we have identified a point person to expedite the prior approval process from our end so that patients can receive their medication approval in a timely fashion. As time goes on, insurance coverage will continue to expand, making it equally accessible to all.
So far, lifitegrast is living up to performance expectations in the management of dry eye disease. Clinicians should make themselves familiar with the robust clinical data as well as the prescribing information so they are comfortable with the medication and can adequately answer patient questions. Rising tides lift all boats, and clinicians are in a better position today to have additional therapies to treat dry eye disease.
Further studies and postapproval experience will answer questions that still remain — such as, are there off-label applications of lifitegrast? What about the treatment of children with dry eye or other ocular surface disease? What is the long-term safety? And until those questions are answered, we will continue to integrate lifitegrast into our treatment regimen to help our patients who have dry eye disease. OM