Improving Quality of Life in Atopic Dermatitis With Targeted Therapies - Episode 12
Expert dermatologists review the positive impact dupilumab has on quality of life for a patient with atopic dermatitis.
Linda Stein Gold, MD: I would like to move a bit deeper and talk about what treatment options are available. Matt, if you don’t mind starting us off, dupilumab was revolutionary for our moderate to severe patients. It changed so many lives. What did we see in the clinical trials? What do we see in real life in terms of efficacy and safety?
Matthew Zirwas, MD: Dupilumab, as you say, is absolutely revolutionary. When it hit the market, we got to see what it did for patients, and wow. It starts working very quickly. We’ve got data out there that within the first week, sometimes less than a week, we start to see improvements in itch and thereby improvements in quality of life. It starts working very quickly. And then the overall efficacy, one of the interesting things in atopic dermatitis is asking which end point we should care about. Very quickly, we’ve got EASI [Eczema Area and Severity Index] scores of 50 to 100, IGA [Investigator’s Global Assessment] scores of 0 or 1, Itch NRS [Numeric Rating Scale] score of 4, then we’ve got quality of life measures. We’ve got Itch NRS 0 or 1, which is an itch-free state.
What’s the right end point? If you just ask patients, would you rather get 50% better or 75% better, they will say 75%; 75% or 90%, they say 90%; 90% or 100%, they say 100%. “OK, I’ve got one that’ll get you 100% better, grow your hair, get rid of your wrinkles and whiten your teeth. I’m going to call that one, it’ll get you to 120%.” That’s the one I want, right?
There are data that give us a hint that EASI-75 [75% improvement from baseline] is where we see topical steroid use drop off. While certainly we want the best outcome we can for a patient, I most closely pay attention to EASI-75. I want to have a level playing field where this is what I’m going to look at from drug to drug. I think EASI-90 or IGA 0 or 1 probably differentiate the drugs a bit better. But something that happens in atopic dermatitis much more so than in psoriasis is the challenge of comparing trial to trial. I know we’re not supposed to do that, but psoriasis results are pretty darn consistent from trial to trial.
In a number of atopic dermatitis trials, even the 2 identical phase 3s that the FDA requires, you’ll see a 10% difference in efficacy…that’s a real difference. So, we really have to be careful in atopic dermatitis comparing trial to trial. If one drug got 90% of people to EASI-75, and another one got 40% of people to EASI-75, I would say the 90% one is better. But EASI-75 versus EASI-70, or EASI-73 versus EASI-67, I don’t think are real numbers. I don’t think we can hang our hat on those differences. Dupilumab, whenever we look at the EASI-75, which is my favorite end point, combined with topical steroids gets about 65% to 70% of people to EASI-75. If we look at a higher end point, IGA 0 or EASI-90, it gets around 50% of people to that end point.
As those of us who do trials know, there are specific definitions of what clear or almost clear means. The way that you should think about it as a clinician, a patient who’s clear is clear. But I’m always like, “What the heck does almost clear mean?” The way that I describe almost clear in a clinical sense is the patient says their eczema is gone. If you say to the patient, “Do you have any eczema?” If they’re an almost clear patient, they’re going to say, “No, my eczema is totally gone.” Whereas you’re going to notice, “Oh, behind your left knee there’s a slight bit of pinkness you didn’t even notice.” That’s almost clear. But for our friends out there who are clinicians and not trialists, when you see the 0 or 1 data, that’s how many patients are going to come back and say their eczema is gone. A score of 1 is not really quite gone. I describe a 2, which is as mild, as a patient who’s going to come in and say, “Compared to where I started, it’s not that bad.” That’s really the clear or almost clear. With dupilumab, we get about 50% of people, whenever you combine it with topical steroids, where the patient would say their eczema is gone.
Safety with dupilumab is really interesting. I honestly say to patients, it is safer to be on this drug than not on this drug. That really comes from the infection data. We know that the risk of skin infections, and I use the term MRSA [methicillin-resistant Staphylococcus aureus] rather than saying staph. Because if you say staph, a patient’s like, “What?” If you say, “Well, you’re less likely to get a MRSA infection,” now the patient’s like, “Oh my God, it’s going to protect me from MRSA? Yes, I need to be on that.” The data for dupilumab has shown a 40% reduction in the risk of skin infections.
With adverse events, we know conjunctivitis is relatively common. The real challenge with the conjunctivitis is there’s no gold standard for differentiating conjunctivitis because you have allergies or you have dry eye, from a drug-induced conjunctivitis. The best numbers we have say that probably 7% of patients on dupilumab will get a dupilumab-induced conjunctivitis. Again, the problem is we know that about 20% of people will get a conjunctivitis, and there’s no gold standard for knowing which 13% were just because you got conjunctivitis and which 7% were from dupilumab. I never use the term conjunctivitis when I’m talking to a patient. I say bloodshot eyes because the patient doesn’t know what conjunctivitis is. If I say bloodshot eyes, they know what that means. So I tell them, “If you get bloodshot eyes, give me a call.” If they get bloodshot eyes, I send them to see an eye doctor. Like we said, we know that about 7% of patients will get dupilumab-induced conjunctivitis. As long as it’s managed appropriately by an ophthalmologist, we can almost always treat through it if we want to.
The other interesting adverse event with dupilumab that’s now in their label is arthralgia. We don’t have great numbers around this, but it’s about 1 in 250 patients seems to be the best number for how many will get what we would call a meaningful arthralgia. Now it’s more common than that if we say a bit of arthralgia. If it’s just a bit of arthralgia, which is relatively common, but those people don’t even notice it. If you ask, they’ll say, “After my shot, my finger hurts for 2 days.” That’s maybe 1 in 20 people, but it’s an irrelevant thing; 1 in 250 people get real arthralgia.
In terms of dupilumab’s impact on quality of life…there are major improvements in anxiety and depression, and quick improvements in anxiety and depression, major improvements in sleep quality. It’s always interesting trying to tease these things out. Is the anxiety and depression getting better because the itch is better or because they’re sleeping better? We don’t really know. It’s almost impossible to tease them out.
Other places where it starts to get interesting, there’s an increase in the diagnosis rate of ADHD [attention-deficit/hyperactivity disorder] in children with atopic dermatitis. We don’t know if that’s a true pathophysiologic association, or if the sleep deprivation makes them more irritable, or if the itching makes them seem more distracted. But the latest study that came out showed there was a decrease in the use of stimulants in children who were on dupilumab. Because people thought they must not really have ADHD, they got diagnosed with it because they were scratching and distracted all the time. Well, if it’s getting them off of their stimulants, I don’t care.
Peter A. Lio, MD: I’ve heard that over and over, a patient saying this gave me my life back, and that’s a powerful moment when you say, wow, you’ve come alive now because this disease had held you back so much. I think those are the kind of end points we’re looking for where people feel like they have control.
Linda Stein Gold, MD: And for the first time, we’re able to deliver that. In the past, we haven’t been able to do that. Matt, that was a lovely overview of the revolution that we’ve seen when dupilumab came into the picture, an IL-4 [interleukin-4], IL-13 inhibitor.
Transcript edited for clarity