The Dry Eye

The new immunomodulator math

There are lots of numbers to consider when physicians prescribe a dry eye treatment.

Now that we have three immunomodulators to choose between, it has become incredibly complex. So many numbers. Many much numbers. And it is not just three times as many things to keep track of, it is exponentially greater. You know, not “three times” but “to the third degree.” Cubed. I am pretty sure that is algebra.

Darrell E. White, MD
Darrell E. White

Whoa.

Anyway, anyone who thought the addition of Cequa (cyclosporine ophthalmic solution 0.09%, Sun Pharmaceutical) to the dynamic duo Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) and Xiidra (lifitegrast ophthalmic solution 5%, Novartis) was going to make our numbers game easier just has not been paying attention over the years. We have now been actively prescribing all three medications at SkyVision for our dry eye patients for 6 months. This is a good time to review the ways that my staff, associates and I have been getting these medications into our patients’ eyes in a way that does not break the bank.

Let us start with efficacy. The most important numbers for us to be aware of are 90 and 10. Ninety percent of patients you see in whom an immunomodulator will be helpful will show both objective and subjective improvement in their dry eye disease with whichever drop you choose. Unfortunately, 10% of patients will not. Even more unfortunately, the 10% of people who will fail is different for each of those drugs. In other words, it’s not just that 10% of people ultimately do not get any relief from an immunomodulator — it is that you cannot guess which one will work. This 10% failure rate does not include those patients who have side effects that are severe enough to prevent them from staying on the medication long enough to decide if it will be truly effective.

Of course, making your choice is dependent on the next important number in our little math lab: How much is this wonder drug going to cost your patient? The first number is by and large the same for all three, and it is outrageous. My last check of the retail price of Restasis, Cequa and Xiidra showed them all bunched somewhere around $550 to $600 per month. This is your first foray into very advanced math. Do you remember studying imaginary numbers? The retail price for these medications is an imaginary number that has no tie to reality. None of your patients will pay this for their medication; every single one will laugh at you if they were ever asked to do so.

This is your introduction to another mathematical field, game theory. You and your staff will now have to enter into the arena and try to game the system on behalf of your patient. To do so, your next numbers are zero and one. Every single insurance company that you query is going to tell your patient that they cover either a single immunomodulator or none at all. Fifty percent of your dry eye patients are typically of Medicare age. These patients will almost always be found to have a single option: Restasis. For 2020 at least, there does not appear to be a single Medicare Part D plan that is covering any medication other than Restasis. Certain markets will have quirky little managed Medicare plans that may be exceptions to this rule, and it is important that you know these quirky players. Otherwise, for your Medicare patients, you live in a universe of one.

How about all of your younger, commercially insured patients? We now have three companies competing for 50% of the pie. Allergan and Restasis are the easiest to understand. If Restasis is covered, there is a copay, which is determined by the price of the medication negotiated between Allergan and a particular pharmacy benefit manager. With or without a preauthorization, your patient will pay precisely this. Allergan to date does not engage in any other programs that facilitate access to Restasis.

Sun Pharmaceutical and Novartis, being the scrappy newcomers to the battle, both have strategies in place to help you, your staff and your patient maneuver through the coverage minefield. The “Ask Iiris” program first introduced by Shire has made it through the two sales events that brought Xiidra to Novartis. Calling an 800 number will enlist the help of the Ask Iiris staff. Ask Iiris will assist in establishing the ultimate cost to the patient and will also assist you and your staff in determining what prior authorization efforts need to be made. If covered, most patients will still go through the “copay based on price” rigmarole. Novartis will “buy down” up to $250 of whatever that number turns out to be, leaving your patient to pay the rest.

Sun has taken the most aggressive approach to date. It has partnered with a group called RxCrossroads. This service will do pretty much what Ask Iiris does, searching to find the greatest amount of coverage for your patient. However, in the absence of sufficient coverage, the RxCrossroads program will cap your patient’s out-of-pocket costs. A 90-day supply of Cequa is capped at $180. For those insurance companies that will cover only a 30-day supply, the cost is capped at $90.

This brings us to our last bit of immunomodulator math. I have shared some of this work before. At the moment, all three immunomodulators are only available in sterile micro-dose dropperettes or bullets. The fill of the Restasis bullet has never changed. Your patient can get at least three full doses for both eyes out of each dropperette. We tell our patients to use each bullet for 24 hours. Somehow, the Sun people failed to get the memo about how we were using Restasis. The Cequa bullets have a similar generous fill. Patients should get at least three doses of Cequa from each bullet as well. Those canny Shire folks were paying much closer attention. The Xiidra bullet contains precisely five drops; those patients who become very good at using Xiidra can get a maximum of two doses from each bullet.

What is left now is just simple division. Your Restasis and Cequa patients can divide the price of a monthly prescription by three to determine their actual monthly cost. Xiidra patients can divide the monthly price by two, cutting their cost in half. It is important to share this with your patient, especially if they blanch at the first number they see. For example, if a 3-month supply of Restasis costs $300, your patient is not actually paying $100 a month, but rather $33.33 if they use it as I just described.

A cautionary note is in order. One of my industry friends worries that infrequent or irregular prescription refills may be interpreted by payers as an indication that these medications are not effective. He is concerned that insurance companies will use this data to refuse to cover these medications on the basis that they must not work if patients are not refilling them “on schedule.” While this is an interesting conjecture, our priority must be getting our chosen immunomodulators into the eyes of our patients at a real cost that is affordable today. We will have to hope that my young friend’s concern is not a premonition.

After all, what the math adds up to depends on who does the math.

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.

Now that we have three immunomodulators to choose between, it has become incredibly complex. So many numbers. Many much numbers. And it is not just three times as many things to keep track of, it is exponentially greater. You know, not “three times” but “to the third degree.” Cubed. I am pretty sure that is algebra.

Darrell E. White, MD
Darrell E. White

Whoa.

Anyway, anyone who thought the addition of Cequa (cyclosporine ophthalmic solution 0.09%, Sun Pharmaceutical) to the dynamic duo Restasis (cyclosporine ophthalmic emulsion 0.05%, Allergan) and Xiidra (lifitegrast ophthalmic solution 5%, Novartis) was going to make our numbers game easier just has not been paying attention over the years. We have now been actively prescribing all three medications at SkyVision for our dry eye patients for 6 months. This is a good time to review the ways that my staff, associates and I have been getting these medications into our patients’ eyes in a way that does not break the bank.

Let us start with efficacy. The most important numbers for us to be aware of are 90 and 10. Ninety percent of patients you see in whom an immunomodulator will be helpful will show both objective and subjective improvement in their dry eye disease with whichever drop you choose. Unfortunately, 10% of patients will not. Even more unfortunately, the 10% of people who will fail is different for each of those drugs. In other words, it’s not just that 10% of people ultimately do not get any relief from an immunomodulator — it is that you cannot guess which one will work. This 10% failure rate does not include those patients who have side effects that are severe enough to prevent them from staying on the medication long enough to decide if it will be truly effective.

Of course, making your choice is dependent on the next important number in our little math lab: How much is this wonder drug going to cost your patient? The first number is by and large the same for all three, and it is outrageous. My last check of the retail price of Restasis, Cequa and Xiidra showed them all bunched somewhere around $550 to $600 per month. This is your first foray into very advanced math. Do you remember studying imaginary numbers? The retail price for these medications is an imaginary number that has no tie to reality. None of your patients will pay this for their medication; every single one will laugh at you if they were ever asked to do so.

PAGE BREAK

This is your introduction to another mathematical field, game theory. You and your staff will now have to enter into the arena and try to game the system on behalf of your patient. To do so, your next numbers are zero and one. Every single insurance company that you query is going to tell your patient that they cover either a single immunomodulator or none at all. Fifty percent of your dry eye patients are typically of Medicare age. These patients will almost always be found to have a single option: Restasis. For 2020 at least, there does not appear to be a single Medicare Part D plan that is covering any medication other than Restasis. Certain markets will have quirky little managed Medicare plans that may be exceptions to this rule, and it is important that you know these quirky players. Otherwise, for your Medicare patients, you live in a universe of one.

How about all of your younger, commercially insured patients? We now have three companies competing for 50% of the pie. Allergan and Restasis are the easiest to understand. If Restasis is covered, there is a copay, which is determined by the price of the medication negotiated between Allergan and a particular pharmacy benefit manager. With or without a preauthorization, your patient will pay precisely this. Allergan to date does not engage in any other programs that facilitate access to Restasis.

Sun Pharmaceutical and Novartis, being the scrappy newcomers to the battle, both have strategies in place to help you, your staff and your patient maneuver through the coverage minefield. The “Ask Iiris” program first introduced by Shire has made it through the two sales events that brought Xiidra to Novartis. Calling an 800 number will enlist the help of the Ask Iiris staff. Ask Iiris will assist in establishing the ultimate cost to the patient and will also assist you and your staff in determining what prior authorization efforts need to be made. If covered, most patients will still go through the “copay based on price” rigmarole. Novartis will “buy down” up to $250 of whatever that number turns out to be, leaving your patient to pay the rest.

Sun has taken the most aggressive approach to date. It has partnered with a group called RxCrossroads. This service will do pretty much what Ask Iiris does, searching to find the greatest amount of coverage for your patient. However, in the absence of sufficient coverage, the RxCrossroads program will cap your patient’s out-of-pocket costs. A 90-day supply of Cequa is capped at $180. For those insurance companies that will cover only a 30-day supply, the cost is capped at $90.

PAGE BREAK

This brings us to our last bit of immunomodulator math. I have shared some of this work before. At the moment, all three immunomodulators are only available in sterile micro-dose dropperettes or bullets. The fill of the Restasis bullet has never changed. Your patient can get at least three full doses for both eyes out of each dropperette. We tell our patients to use each bullet for 24 hours. Somehow, the Sun people failed to get the memo about how we were using Restasis. The Cequa bullets have a similar generous fill. Patients should get at least three doses of Cequa from each bullet as well. Those canny Shire folks were paying much closer attention. The Xiidra bullet contains precisely five drops; those patients who become very good at using Xiidra can get a maximum of two doses from each bullet.

What is left now is just simple division. Your Restasis and Cequa patients can divide the price of a monthly prescription by three to determine their actual monthly cost. Xiidra patients can divide the monthly price by two, cutting their cost in half. It is important to share this with your patient, especially if they blanch at the first number they see. For example, if a 3-month supply of Restasis costs $300, your patient is not actually paying $100 a month, but rather $33.33 if they use it as I just described.

A cautionary note is in order. One of my industry friends worries that infrequent or irregular prescription refills may be interpreted by payers as an indication that these medications are not effective. He is concerned that insurance companies will use this data to refuse to cover these medications on the basis that they must not work if patients are not refilling them “on schedule.” While this is an interesting conjecture, our priority must be getting our chosen immunomodulators into the eyes of our patients at a real cost that is affordable today. We will have to hope that my young friend’s concern is not a premonition.

After all, what the math adds up to depends on who does the math.

Disclosure: White reports he is a consultant to Allergan, Shire, Sun, Kala, Ocular Science, Rendia, TearLab, Eyevance and Omeros; is a speaker for Shire, Allergan, Omeros and Sun; and has an ownership interest in Ocular Science and Eyevance.