Lifitegrast improves clinical signs and biomarkers of patients with DED: A Q&A with Dr. James Thimons

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A recent study evaluated the efficacy of lifitegrast, a topical anti-inflammatory therapy approved for the use in dry eye disease, in improving the clinical signs and biomarkers in patients with the disease. James Thimons, OD, who presented results from the study in a recent American Academy of Optometry meeting poster presentation, sat down with Optometry Times in an exclusive Q&A to discuss these findings.

Q: First, can you summarize some of the findings?

A: Yeah, let me give you a overview of the intention of the study. And then I think we could break it down into more of its granular elements.

The goal of the study was to look at biomarkers that are commonly used in clinical practice by doctors who are examining patients. Items such as OSDI, tear osmolarity, central corneal staining with fluorescein, lissamine stain, those types of tear breakup time. Those elements are what doctors typically use but historically, in most studies, either the primary or secondary endpoints were not taken beyond one or two of those. So this was an attempt at a real life study to determine the efficacy of lifitegrast in a 12 week application on those 6 elements, and subsequent to that, how that would then be translated into reasonable expectations in utilization of the drug and clinical care.

Q: That's fabulous. So can you tell me, what did you find from the study?

A: Well, the 2 primary endpoints were tear osmolarity and OSDI, and both of those showed initial and continued improvement over the entire period of study, significant improvement to p<0.001, which is outstanding. I think, from a practical perspective, if you look at all 6 of them, I was very impressed–having not run the data myself, but been a part of the study–very impressed with the overall performance across all 6 metrics. So all 6 of the biomarkers showed improvements, some more than others, but significant enough that it would be identifiable by a clinician in physical examination of the patient. And I think it's really useful for doctors to have a time frame, and as early as 2 weeks in the study, there was appreciable improvement, although statistically significant, improvement continued to grow towards the latter part of the study to a very high level. So I was really happy with that, because most of the surface management drugs, immunomodulators, or in this case, lifitegrast, which is a slightly different mechanism of action, are not historically noted for their rapidity of onset. Lifitegrast did have 2 week data, positive data in 2 of the 4 original FDA studies. But this was an attempt to display that across a much larger spectrum of political analysis.

Q: I know you just mentioned a couple of surprises that you found, but were there any other things that surprised you in the data?

A: Well, one of the pieces that I was very impressed with, because it's something that I do use daily sometimes, on every dry eye patient, one of my basic assessment points is the use of lissamine supravital staining is, to me, 1 of the true markers, the true biomarkers of current disease state, and also a differentiator as to the nature of the patient's ocular surface complaints. In a real world setting of thousands of patients to be able to evaluate them, all of which had dry eye complaints, about 15 plus percent would be pure aqueous insufficiency, and another 35% would be aqueous insufficiency and your lid. And then a 50% base would just be pure posterior lid disease. The use of lissamine is one of the great differentiators of which of those entities is present and at what level, so it directs the care of the patient very pleasantly and pretty, pretty efficiently. If you're not using it, it makes it more complex. In this study, that biomarker was notably improved in 12 weeks. Very impressive. So the patient went from 108 down to .13, which is a 10 times reduction in overall lissamine stain over the course of the 12 week treatment period. And those types of physical characteristic changes inevitably produce a patient's improvement in symptoms, because signs typically precede symptomatic relief, so you have a little bit of lag between the improvement of a sign and then the overall awareness on the part of the patient that there's symptomatic relief. So I was very impressed with the fact that in 12 weeks you had that remarkable change in that and also corneal staining, which is very difficult to eradicate, was significantly improved as well.

Q: I know you've also alluded frequently to the rapidity of the effects on signs and symptoms but are there any other comparisons to other dry eye therapies or to other immune modulators that you can draw from this data?

A: This data specifically did not address other pathways for treatment. There have been other studies that have done that, they've gone head to head. But in this one, there was actually a Phase 4 from another company that looked at a switch study, which is useful. Switch studies are interesting and sometimes useful, but one has to take those with a little bit of a perspective on the power of the study. That said, that's the only one that I'm aware of where there was a head to head. In most instances, I don't think companies would typically do that. The alternative though is that if you look at the data from different studies, standalones, and you compare it to this, this really represents quite well against any of the other drugs in this space. Obviously, most of those are some form of cyclosporine. And as a result of that, it makes it a very simple choice because of its ease of use and general acceptance by patients. So I think the general direction of the study was to help clinicians understand relevant and reasonable choice in a fairly competitive space and looking at the biomarker impact that these this drug had in that 12 week period. I think it makes it very clear that this is quite a good choice if you need to treat a patient for ocular surface issues.

One thing that it didn't do because they looked at meibomian gland status; it did not affect meibomian gland status. That's not a surprise, but I thought it was an interesting sidebar in the study. There have been other claims to that effect from different directions that I thought were a little broad. This one specifically said, let's just look at it, we've already examined the vision. The lid margin itself improved predominantlyº34 of the 50 patients showed improvement–and there were some that were no changes, was a small number that did not improve or worsened. But I think the issue there is when you reduce inflammation on the ocular surface, the secondary effect is that the inflammatory, hyperinflammatory induction that's produced by the change of tear film, which coats the lid margin, will diminish, and therefore a decrease in the inflammatory mediated changes at the lid, which are almost always hyperemia and some congestion of the vessels. So that did improve, and that improved quite nicely.

Q: That's super interesting. So do you just want to wrap up with a few key takeaways?

A: Yeah, I think the takeaway is, in a very complex space, it's useful for clinicians to have relevant data to make their clinical decisions from, and also it's very important to be able to understand the relevance of the data as it relates to the rate of change and the expectation for change over time. I think that's probably the biggest take out here is you know from the study that the 6 biomarkers expectations are that you would have a positive response in the vast majority of patients, very high percentage, and that that would occur within a reasonable period of time, within 2 to 3 weeks. So if I see a patient and initiate treatment, I really want to know a few basics about the drug. Obviously, acceptance on the part of the patient, persistence of effect, but one of the most important is: how long should I let the patient go before they come back, so that I can understand whether the drugs working or not? And this study, I think, really helps define that time period for the clinician and expectation in a very relevant and significant way.