Annual review of anti-inflammatory medications

Issue: September 25, 2017

ByDarrell E. White, MD

For the past 2 years I have jokingly labeled this month’s column my annual lifitegrast edition. Now that Xiidra has been on the market for a year, it is time to evaluate it in the context of its competitors. As this part of our world matures and becomes less controversial and more a part of care standards, Xiidra becomes another tool in the anti-inflammatory kit. After a year in the game, we are getting to know Shire while also learning some new things about the established players Allergan and Bausch + Lomb.

Let us go on a walkabout.

There is no longer any real controversy about whether or not inflammation is a key component causing dry eye disease. It has long been my contention that it does not matter whether inflammation is the original inciting cause or if it is simply the grease that keeps the negative cycle spinning. If you are going to treat DED, you are going to be treating inflammation. In so doing, you now have three arrows in your quiver: loteprednol, cyclosporine A and lifitegrast.

Original medications

Contrary to the contemporary zeitgeist, the original DED anti-inflammatory drop was Lotemax, a loteprednol suspension brought to market by Bausch + Lomb. Did you know that the original Lotemax had an on-label indication for superficial punctate keratitis? Crazy, huh? Can you imagine having that kind of indication today and not telling everyone? The dirty little secret is that loteprednol in all of its various forms is an incredibly effective DED medicine. At SkyVision, we have found it to be better at making a positive InflammaDry (Quidel) become negative than any other drug, with the expected improvement in patient symptoms.

Lotemax, Lotemax Gel, Alrex and any number of generic formulations are available. If it is so effective, why don’t you think of it more often? Loteprednol is unfairly smeared with safety issues associated with other topical steroids. On the ground the incidence of elevated IOP and cataract formation is quite low, although you are certainly obliged to see a patient on any of the above a bit more frequently. One clear advantage for any of these is that generics may enjoy favorable insurance coverage in your market.

You can make a case that Restasis belongs on a Mount Rushmore of ophthalmic medications along with Pred Forte, Timoptic and Macugen, the first anti-VEGF. Without Restasis, we probably would not have a real DED category in the anterior segment. Cyclosporine A in an Endura vehicle, whether dispensed from vials or from a multi-dose bottle, is a highly effective anti-inflammatory treatment. It is still a challenge to use because of the nature of the drug and its mechanism of action. There is a refractory period of 4 to 6 weeks before the drug actually kicks in. Symptoms can (and should) be reduced during this time with the use of adjuvant loteprednol.

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Much has been made of this delay in the onset of symptom abatement with Restasis. Personally, I have long taken the tack that this is simply an opportunity to educate our patients about the chronic nature of DED. It is much, much easier to help your patients adhere to therapy if you see them in the office at regular intervals, especially early on in their journey. We always see new Restasis patients at the 6-week mark, and we insist that they do not discontinue treatment until that visit. Restasis is as important today as it has been at any time in the last 14 years.

Newest medication

Has Shire had a big impact on the DED market, or what? If memory serves, there was a 30% increase in DED prescriptions in the last 6 months of 2016 after Xiidra hit the ground. While the rate of growth has leveled off a bit for Xiidra prescriptions, it continues to grow at an amazing pace. Why? Well, Xiidra is a highly effective anti-inflammatory treatment that tends to work within the first 2 weeks or so on signs, symptoms or both. It has side effects that you must share with your patients: instillation discomfort, dysgeusia and post-installation blurred vision. These are pretty mild most of the time, but adherence to therapy is much higher if you prepare your patients.

Bottom line? Xiidra works unbelievably well, and having it available has made DED care better.

Upcoming challenges

Let us not think this all portends nothing but rainbows and unicorns in our DED world. We will be increasingly challenged in our clinics by the silly games played by the pharmaceutical companies, insurance companies and pharmacy benefit managers (PBMs). It will be you and your patients who will suffer from this. For instance, your barrier to using loteprednol is the obdurate refusal of insurance companies and PBMs to acknowledge that there is a difference between steroids. That, and Bausch + Lomb’s continued refusal to fight that battle.

Game of Thrones has nothing on the Restasis-Xiidra battles to come. Do you routinely try to give your patients samples when they start a new medicine? I do. All the time. Say so long to samples of Restasis in vials, though. Allergan is going to push the multi-dose dispenser exclusively. The comparison with Xiidra vials may be seen as an advantage, there is the issue of multiple production lines and FDA approvals, and let us just say that the math favors bottles over vials for Allergan. Nobody asked me (seriously, nobody did), but put me down as favoring sampling both. Why make me change a successful prescribing protocol?

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Be ready to learn some new vocabulary. “Step therapy” is about to enter your lexicon. In a major victory for Shire, Xiidra is a Tier 1 medicine for all Anthem patients. Step therapy means that patients must have a clinical failure on Xiidra before they can have another medication covered. This was probably an Anthem requirement, but it is a crushing defeat for overworked staff members and overwhelmed patients. Your Restasis patients covered by Anthem will now have to undergo a trial of Xiidra and “fail” in order for them to be able to renew their Restasis prescription, no matter how long they have taken it. No “grandfathering.” Ugh.

The good? Where once we had almost no options we now have three. We will soon see at least two more cyclosporine A products. Who knows how many new options are coming? The bad and the ugly news is that you, your staff and your patients are still collateral damage in the take-no-prisoners battles being waged over paying for these highly effective medicines.

For more information:
Darrell E. White, MD, can be reached at SkyVision Centers, 2237 Crocker Road, Suite 100, Westlake, OH 44145; email: dwhite@healio.com.

Disclosure: White reports he is a consultant for Bausch + Lomb, Allergan, Shire and Eyemaginations; is on the speakers board for Bausch + Lomb, Allergan and Shire; and has a financial interest in TearScience.