3 Years of Real-World Data for an AD Biologic

Elizabeth Swanson: 

Hello, everybody, and welcome to another Type 2 Inflammation Journal Club brought to you by Practical Dermatology. I'm here with an illustrious guest today, you guys. He is here live, in person. Virtually for you guys, but live for me. And he is none other than Dr. Neal Bhatia. 

Welcome, Dr. Bhatia. 

Neal Bhatia: 

Elizabeth Swanson, I'm, I'm honored to be on the receiving end of the interview and being the interviewee of- 

Elizabeth Swanson: 

Ooh. 

Neal Bhatia: 

... of, of the, the great Dr. Lisa Swanson. 

Elizabeth Swanson: 

This is a little bit of a reversal of roles here. 

Neal Bhatia: 

I, I am... Listen, I, I will not talk about the tales of Ophelia or, uh- 

Elizabeth Swanson: 

(laughs). 

Neal Bhatia: 

... or anything to do with the new album. We're, we're strictly going to talk about Type II inflammation. 

Elizabeth Swanson: 

And you know what is true about Type 2 inflammation, Dr. Bhatia, is that it's opalite. 

Neal Bhatia: 

It is opalite. (laughs) It's true. 

Elizabeth Swanson: 

(laughs). 

Neal Bhatia: 

I missed out on that one. I almost had you there. 

Elizabeth Swanson: 

(laughs) And so we are here today to talk about a wonderful article published by Dr. Neal Bhatia in the amazing journal, Dermatology Therapy, and it documents the PROSE registry and what we learned from the PROSE registry. And so my first question today, Dr. Bhatia, what is the PROSE registry? 

Neal Bhatia: 

PROSE registry is a 3-year study involving patients who are established on dupilumab, basically looking at their outcomes to ages 12 and up primarily. We, the study really was focusing on those who were established and who could give a good history, obviously. But more importantly, just looking at quality of life, looking at the itch burden, looking at any potential progression to asthma, perhaps, or any other change in their outcomes. And more importantly, it's just, it was a really comprehensive database type registry looking at, you know, US and Canada patients who, again, had achieved good outcomes. Their NRS scores were down and their ODS or overall disease severity was down. And it was a pretty well-powered registry study. 

There were about 857 patients on the article, 40 some percent were male, you know, and maybe, probably about 7% adolescents in there. And again, the vast majority, again, achieved that NRS score of 0 to 1, which were primary clinical endpoints, which is key. The other thing, again, even by 3 years, those who completed the registry, again, they also had overall disease severity scores of 0 or 1, maintaining their clearance. And again, it's pretty significant compared to, you know, the fewer that were not there at the baseline of the study. 

So again, you know, it's a very real world, you know, not trying to, you know, reinvent any kind of wheel, but it shows the longevity and the safety of dupilumab for that timeframe. I think we're all familiar enough now having, you know, seen Dupixent on the market for a decade nearly, and we were part of the early phase study we did, SOLO and CHRONOS which put the phase 3 on the map. 

More importantly is again, just, you know, looking at how you can keep these patients on drug, not have to think about, you know, is there a time to take them off? Do they need a holiday? But I only see these patients probably once a year, which is probably, in your Boise experience, probably very similar. 

Elizabeth Swanson: 

Very similar, very similar. One big question I had, I wasn't familiar with ODS, overall disease severity score. Tell me about that. Why'd you choose it? What does it mean? Why is it important? 

Neal Bhatia: 

Yeah, I think ODS is meant to talk about improvement in the overall disease severity. So it's meant to be more of a dynamic score than an isolated score because you're thinking about, OK, week 16 endpoints, are you reaching clear or almost clear? Are you reaching... You know, to me, that's more of, like, a modified way of talking about IGA in a real trial. In a registry trial or a, you know, something like this that's more observational, you know, the change in the disease severity is really the measuring stick of what you want to watch for. 

Elizabeth Swanson: 

Mm-hmm. 

Neal Bhatia: 

So I would say this is probably something more of a dynamic score than just an isolated across the finish line like we do with IGA. 

Elizabeth Swanson: 

And it encompasses both itch clearance and skin clearance, both? 

Neal Bhatia: 

Right. Because, again, breaking that itch scratch cycle and getting that NRS score down will lead to a improvement in overall disease severity, the objective disease severity. So I think all of that, you know, kind of goes hand in hand. 

Elizabeth Swanson: 

And the patients in the study were 12 and up. Did you see... You talked about how many percentage of patients developed asthma. Did you see any benefit for patients on dupilumab when they were 12 and up? I think about, like, my pediatric patients. I think there's a window of opportunity where if I intervene with dupi, I likely reduce the risk of asthma. 

Neal Bhatia: 

Yeah. 

Elizabeth Swanson: 

Did you discern that for the 12 and ups, or has that ship kind of sailed? 

Neal Bhatia: 

I think it's probably too late in the game when 12 and up, you know, is not being looked at like 6 months enough. And you know more than I do about how childhoods have changed with dupilumab's indication at 6 months and up. You can rescue a lot of these kids from the misery of eczema and flare. 

And it goes back to the atopic march idea, our good friend, Dr. Hebert, who put her stamp on that years ago. I think there is some definite value to that because, again, if you look at the TH2 side of the wall of inflammation, which we now know swims with everything else, but as, you know, we explained atopy to the patients in the same way. We say asthma to the lungs, allergic rhinitis to the nose, eczema to the skin is all part of the atopic dialysis. 

Is there a progression of that time, you know, that probably should be looked at between 6 months and 12 years? That more for your pediatric dermatology world to tell us than otherwise. But- 

Elizabeth Swanson: 

Yeah. 

Neal Bhatia: 

... my thinking is, you know, if I... And we had 15 patients enrolled in the trial. We had a bunch of people drop out, unfortunately, because within 3 years, they moved. Some of them lost access to insurance coverage because, again, a registry study doesn't pay for their drug. It's them having insurance. 

So I had, I probably had... I actually, I think we just closed on our last subject, last month, and he did, he went the distance. He went 3 months, 3 years. I had a couple other patients who went the distance, and then others unfortunately had to drop out. But, you know, most of them we saw for a least a year and saw how well they did. 

Elizabeth Swanson: 

Yeah. 

Neal Bhatia: 

So, but I don't... Fortunately, I didn't have anyone who, um, reported any issues with asthma or anything else. 

Elizabeth Swanson: 

Gotcha. And, you know, we've had the most experience with dupi, but now we have all these new kids on the block, these new systemics. Eventually, we'll be able to see some long-term data with them. How important are long-term results like this as we move forward and as the other, these other biologics kind of settle into the space? 

Neal Bhatia: 

Yeah. Well, I totally agree with you. I think, you know, you look at tralokinumab and lebrikizumab, they're all going to have 3-year data, 5-year data. I don't know if they will follow along and do a similar registry- 

Elizabeth Swanson: 

Mm-hmm. 

Neal Bhatia: 

... like dupilumab. I mean, dupilumab had the advantage of being the first. 

Elizabeth Swanson: 

Right. 

Neal Bhatia: 

So they got to set that up. I think the other part too of the equation and you throw in Type 2 inflammation, is there a mechanistic benefit of blockade of the receptors of 4 and 13 over 13 alone or the cytokine of 13 alone? And you can even throw in the idea of 31 alone. 

Elizabeth Swanson: 

Mm-hmm. 

Neal Bhatia: 

When you're changing feedback loops and when you're changing the overall TH2 surveillance, is that going to change any kind of progression to something else? And again, talk about asthma, talk about it, you know, prurigo nodularis and the itch-scratch cycle, is all that in place. I think there's definitely some talking points that go along with maybe how that blockade is perhaps, you know, going to be a little bit different than just blockade of one- 

Elizabeth Swanson: 

Mm-hmm. 

Neal Bhatia: 

... one target. So I don't know if that's going to be superior or not, but I don't think that was really the purpose of this study. I think this is really just observing them crossing the finish line and staying good for that timeline. And I, you know, we know from the phase 3 data of all those trials that we shouldn't have to worry too much. 

Elizabeth Swanson: 

One kind of random question about the PROSE registry with dupilumab, did you look at how people were dosing their dupi? Because I know in real life, you know, for patients 12 and up, they're likely on every 2 weeks dosing, but sometimes you can space them out. Did you guys take into account or did you tell the patients, "You must stay on every 2 weeks"? 

Neal Bhatia: 

Yeah. So they had to answer the diary. I believe one of the questions was, did your dosing get interrupted or change? But I think the vast majority, if not all of our subjects, fortunately, I think they all stayed on every other week. 

Elizabeth Swanson: 

Gotcha. 

Neal Bhatia: 

So, you know, there are going to be times they skip a dose. There are going to be times that say, "Oh, I'm better. Let me do a month, every 4 weeks instead of 2." Uh, you know, I mean, everyone's going to cheat a little bit. 

Elizabeth Swanson: 

Yeah. 

Neal Bhatia: 

And that's how the game is played. But we also know from the original pivotal trials that, you know, Sanofi and Regeneron ran, I mean, they did it once a week- 

Elizabeth Swanson: 

Yeah. 

Neal Bhatia: 

... and it didn't show any benefit. And they dose that once every four weeks, didn't show any benefit. 

Elizabeth Swanson: 

Mm-hmm. 

Neal Bhatia: 

You know, it's different than tralokinumab that has every-4-week data, you know. Different than lebrikizumab, which has, you know, variability. 

So I think from that standpoint, I think there was some quality assurance that the patient stayed on their every-other-week dose. 

Elizabeth Swanson: 

Sure. Of course, of course. That makes sense. 

Neal Bhatia: 

Yeah. 

Elizabeth Swanson: 

Well, wonderful, Dr. Bhatia. Thank you so much for joining us on this Type 2 Inflammation Journal Club. I hope everybody got something out of it. I learned a lot. I know I learned a lot. 

Neal Bhatia: 

Well, now that's flattering. 

Elizabeth Swanson: 

Yeah. 

Neal Bhatia: 

For you to learn something from me, Dr. Swanson, I'm going to celebrate that. 

Elizabeth Swanson: 

I love it. I love it. Well, thanks, everybody, for tuning in.