Compliance, Adherence - Whatever, Just Put the D*mn Cream On...

Summary

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Podcast Summary: Derms on Drugs

Episode: Compliance, Adherence – Whatever, Just Put the D*mn Cream On...

Date: March 7, 2025
Hosts: Dr. Matt Zirwas, Dr. Laura Ferris, Dr. Tim Patton
Special Guest: Dr. Steve Feldman (Wake Forest University)

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Episode Overview

This episode explores the perennial dermatology challenge of patient adherence (a.k.a. compliance) to treatment regimens—particularly with topical medications. Through expert discussions, humor, and a special appearance from Dr. Steve Feldman—a leading voice in adherence research—the hosts dissect recent clinical trial data, illuminate the real-world difficulties of getting patients to “just put the cream on,” and sift through what really matters for dermatology outcomes. The panel also tackles recent advances in oral and topical drugs and closes with their signature light-hearted biosimilar trivia.

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Major Discussion Points & Insights

1. New Therapies for Psoriasis and Atopic Dermatitis

• Icotra Kinra (J&J2113 oral peptide, IL-23 inhibitor)

  • [01:38 - 08:33]
  • Dr. Ferris (First author on the study) introduces the 52-week extension data from the FRONTIER 2 study.
  • Oral peptide, small systemic absorption, blocks IL-23 receptor. Not unique to J&J; other oral peptides exist.
  • Main outcomes at 52 weeks:
    • PASI 75: 76.2%
    • PASI 90: 64.3%
    • PASI 100: 40.5%
  • Key Quote:
    "I do think that there are probably patients who prefer an oral medication and that is why I'm so excited to talk about this with our guest." — Dr. Ferris [06:43]
  • Discussion of efficacy compared to existing biologics (e.g., Cosentyx, Illumia, Skyrizi):
    • Similar to mid-tier biologics, below the most effective injectables.
    • Safety clean, some dosing drawbacks (needs to be taken fasting, BID in the trial).
  • Adherence tie-in: Oral administration may improve preference but fasting/BID might limit adherence.

• Tapinarof (VTAMA cream) in Atopic Dermatitis

  • [08:33 - 15:57]
  • First non-steroidal, non-TCI topical for kids as young as age 2.
  • Derived from “worm poop”, minimal systemic absorption, no boxed warnings, minimal baggage, works quickly.
  • Dr. Zirwas: “...It’s effective, it’s fast and there’s no baggage. It’s an interesting thing to see if this is going to change pediatric AD the same way that Opzelura changed adult AD.” [10:41]
  • Folliculitis is a drawback (~10%), but otherwise well-tolerated.
  • Comparison to Zoryve (roflumilast): efficacy likely a bit higher for VTAMA, but Zoryve has known MOA, preferred by peds derms.

• Cabtreo (Clindamycin, Benzoyl Peroxide, Adapalene gel) for Acne

  • [16:19 - 22:52]
  • First triple combination topical.
  • Study showed modest improvements in inflammatory/non-inflammatory lesions.
  • Quality of life metrics not superior to dual-combination products.
  • Industry-sponsored design discussed with skepticism.
  • Dr. Patton: “Like, why is it being sold to us this way?...They sell it to you in the most...it's deceptive, right?” [20:39]

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2. Patient Adherence vs. Drug Efficacy – Real World Practice

• Patient Non-Adherence is Rampant

  • [23:55 - 26:45]
  • Dr. Feldman recounts studies (including one with electronic medication caps) showing no patients using topical regimens as prescribed (e.g., 80% adherence was achieved by zero participants).
  • Key Quote:
    "Not a single person used it 80% of the time. Not one." — Dr. Zirwas on Feldman's study [25:06]
  • Efficacy gaps between oral and injectable drugs may reflect adherence issues, not pharmacology.

• Trial Setting vs. Real World

  • In trials, blister packaging and frequent follow-ups improve adherence.
  • Blister packs and colorful packaging could help in real life—“Nothing should be packaged in a bottle, especially a beige bottle that's designed to blend into…” — Dr. Feldman [27:01]
  • Frequent follow-up is analogous to piano lessons:

    “If a piano teacher said, here's your sheet music, practice every day, I'll just see you at the recital in three months...that recital is going to sound abysmal.” — Dr. Feldman [28:13]

• Does Motivation Matter?

  • Desire for clear skin (e.g., severe acne, eczema, even painful diseases) does not guarantee adherence.
  • Even for conditions like gonorrhea, patients struggle to complete a mere 7-day course.

  • “But they won't take a pill. The stuff we ask them to do, the stuff you're asking your acne patient to do for three months, they're not.” — Dr. Feldman [38:50]

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3. Strategies to Improve Adherence

• "Idiot Proof" Drugs vs. Behavioral Interventions
  • Once-every-few-months injectables may bypass the adherence issue.
  • On the other hand, adherence can be improved with effort: short intervals between visits, accountability mechanisms.
  • Ideas range from quick turnaround follow-ups (“see you in three days”) to future tech (deepfake AIs checking in as their doctor).
  • Key Quote:

    “It will cost nothing to create this sense of accountability that drives people's behavior, you know?” — Dr. Feldman [34:50]

  • Simple interventions:
    • Office-administered medications (lightbox as excuse for daily topical use).
    • Accountability check-ins dramatically increase usage.

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4. Memorable Quotes & Moments

• On Study Designs:

  "This is an advertisement by the company that's masquerading itself as a, you know, like an independent scientific inquiry.” — Dr. Patton [19:41]

• On Doctor Influence:

  "You're reminding me of something...do you think maybe the reason you think CeraVe works so well is because you're telling your patients, oh my God, this is a miracle...?"
  — Dr. Feldman (paraphrased by Dr. Zirwas) [29:25]

• On Adherence as a Provider Problem:

  "If the lettuce is not growing, well, you don't blame the lettuce. All right?"
  — Dr. Feldman [36:07]

• On Accutane Success:

  "Maybe that's why Accutane works so well…you have to see those patients every month because of the whole iPLEDGE thing."
  — Dr. Patton [39:07]

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5. Notable Fun Segment: Biosimilar or Science Fiction?

[40:28 - 45:26]

• A rapid-fire trivia game where the hosts and guest try to distinguish whether names are of new biosimilars or from science fiction.

  • Tie game among all four.
  • Lighter moment underscores how confusing drug names can be versus sci-fi!

  “The Humira ones are good. The ones that are coming out for Stelara…I mean, every single one sounds like a science fiction character. It's awesome.” — Dr. Patton [45:13]

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Key Timestamps by Segment

| Timestamp | Segment/Discussion | |-----------|---------------------------------------------------| | 01:37 | Icotra Kinra oral peptide for psoriasis | | 03:38 | Phase 2b extension results and clinical use | | 04:50 | Efficacy comparisons and practical limitations | | 08:33 | Tapinarof (VTAMA) in pediatric atopic dermatitis | | 12:48 | Comparison with Zoryve and real-world perspectives| | 16:19 | Cabtreo triple combo for acne | | 19:26 | Critical take on clinical trial and outcomes | | 23:55 | Dr. Feldman on adherence: studies and insights | | 25:06 | Real rates of topical use | | 27:01 | Packaging and behavioral cues for adherence | | 28:13 | Piano lesson analogy for follow-up frequency | | 34:50 | Deepfake doctor accountability idea | | 36:07 | "Don't blame the lettuce"—responsibility for adherence| | 38:50 | Why even severe symptoms don’t guarantee adherence| | 40:28 | “Biosimilar or Science Fiction?” trivia game | | 45:26 | Wrap-up and closing remarks |

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Actionable Clinical Pearls

• Adherence is the real limiting factor in dermatologic outcomes—not necessarily drug efficacy.
• Oral drugs may provide convenience but have their own adherence hurdles (fasting/BID requirements, etc.).
• Simple changes—colorful packaging, frequent short-interval follow-ups, explicit positive framing (“miracle cream!”)—can influence patient behaviors.
• Don’t assume patient motivation equals proper medication use; it almost never does.
• If a patient’s condition isn’t improving, suspect lack of regular use before changing/adding treatments.

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Memorable Quotes – Quick Reference

• "Not a single person used it 80% of the time. Not one." — Dr. Zirwas, [25:06]
• "If the lettuce is not growing, well, you don't blame the lettuce." — Dr. Feldman, [36:07]
• "The stuff we ask them to do for three months, they're not." — Dr. Feldman, [38:50]
• "Nothing should be packaged in a bottle, especially a beige bottle..." — Dr. Feldman, [27:01]
• "It will cost nothing to create this sense of accountability..." — Dr. Feldman, [34:50]
• "This is an advertisement by the company that's masquerading itself as a, you know, like an independent scientific inquiry." — Dr. Patton, [19:41]

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For those who haven’t listened:
This episode will confirm your suspicions, challenge your assumptions, and offer real, pragmatic advice about the biggest unsolved problem in dermatology: patient adherence. In between laughter and biosimilar-based word games, the hosts and Dr. Feldman remind clinicians that most of the therapies in dermatology work—if only we can convince our patients (and ourselves) to use them as intended!

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Transcript

[A]

Welcome to Derms on Drugs, a video podcast brought to you by Scholars in Medicine. Terms on Drugs is where cutting edge dirt meets hello to mediocre comedy. I'm Matt Ziers, and each week I'm joined by my residency buddies Laura Faris and Tim Patton to use our 60 years of combined derm experience to discuss, debate and dissect the hottest topics in dermatology. It's everything you need to know to be on the cutting edge of derm, and it'll be the most fun you've ever had while actually learning something useful. So tune in every Friday only at Scholars in Medicine, Spotify and Apple podcasts. And everybody, I gotta tell you, I am so excited today for our deep dive. We've got one of my, I don't even know if I'd say one of maybe my favorite person in all of dermatology. We've got Dr. Steve Feldman from Wake Forest University to talk about some of the aspects of adherence. Right. We're supposed to call it adherence, not compliance. But it is going to be a great discussion about, you know, what do we expect with some of these drugs and should they be better or worse and all that kind of stuff. But let's go ahead and get into it. I'm going to kick it over to Dr. Ferris for our first article of the week.

[B]

Thanks, Matt. I hope I am your second favorite North Carolinian, but I'll start with. So I am going to talk about Frontier 2, a phase 2b term extension study of the oral peptide J&J2113, which now we can actually call by its proper name, Icotra Kinra, for moderate to severe plaque type psoriasis. So what is this drug? This is an oral peptide. So it is administered orally, but it actually binds. It's a small peptide. It escapes the gut and it goes into the bloodstream and it. It binds to and blocks the IL23 receptor.

[A]

Faris. How does that. So you're first. I'm gonna tell everybody. Dr. Faris is first author on this paper, so I think of her as the world expert on. How do you say it again?

[B]

Icotra kinra.

[A]

Ecotra kinra.

[C]

How.

[B]

Now I'm gonna find out. I'm saying it wrong.

[A]

So how does it get, how does it get absorbed? Like it's a peptide. It shouldn't get like. I think of it as having like 1% bioavailability.

[B]

It has extremely low bioavailability.

[A]

But it should have any. It should have zero.

[B]

It has some. So it is. There's a small amount, it is able to escape through the GI tract. So it actually is systemically absorbed.

[A]

So is this a like proprietary thing that they've got a special way of doing this or should we expect like in a couple of years Doopie is going to have a DUPY oral.

[B]

And so this is not the only oral peptide. Right. So there are other oral inhibitory peptides, you know, particularly of IL17. There's one. So, you know, so this is not something that only Johnson and Johnson or Janssen has. Like, do I have the recipe and can I make it up in my kitchen? No. So there are other proprietary aspects to it. Yes.

[A]

Okay.

[B]

All right.

[A]

All right, there we go. Go ahead.

[B]

So this is it. So the 16 week data were already published and this is sort of the 52 week extension. So, you know, what did we see? You know, basically what we saw at 16 weeks held true at 50 really was, you know, kind of nicely consistent out to 52 weeks patients who are on placebo to week 16. When they crossed over to the high dose, which was 100mg PO bid, they caught up and really did just as well as, as that group, basically, or similarly. So what does that top line result look like? Pasi 75 response of 76.2% Pasi 90 of 64.3%. Pasi 100 of 40.5%. So and then safety wise, really, there was like nothing unique here. These patients were, you know, tested for TB prior to being and at screening there was kind of nothing exciting, nothing unexpected, no real like GI side effects with this medication. So, you know. Yeah, go ahead.

[A]

Where will we use this? So I'm looking at these numbers. I'm no psoriasis expert, but it looks to me like this is in the ballpark of maybe better than a stellar, not as good as a Cosentyx. Is that so?

[B]

That's interesting you would say that. So if you look at the data for Cosentics, you know, there's lots of studies with Cosentix, but it's a Pasi, 100 is about 40%. With Cosentix, Pazzi 90 is about 57. So it's a little lower than okay. If you look at Illumia, Pazzy 75 is like 64. So kind of think of it in the cosentic.

[A]

Patton's like mumbling in the background.

[B]

Yeah, what are you mumbling?

[A]

What are you mumbling about Patton?

[D]

No, that Cosentix and Illumia aren't the gangbuster drugs. Like I, I Think it's on par kind of in that neighborhood where it's not gonna, it doesn't seem like it would touches the skyrizi. The term.

[B]

It'S not going 152 weeks for sky race is about 60. Okay. So it is not going to be the same.

[D]

How does, where does so tic2 shake out? Like is it going to take on so tic 2 is so tick 2 dead. Now we have another oral medication or.

[A]

I think this is way better than SOTIC2's data.

[B]

This is a little bit, a little bit better than so tic tube. Right. And you don't have any of the, the jack concerns.

[A]

Yeah.

[D]

Because jacks cause cancer and heart attacks.

[A]

And they do not cause cancer.

[D]

That will tell you that that's all true.

[A]

My vociferousness has nothing to do with how much I make from Abbvie or Pfizer or Lilly.

[D]

I know I was teasing you. I know that how you feel about that.

[B]

I think you know not to not make this all about Matt, but I do think that, you know, there are probably patients who prefer an oral medication and that is why I'm so excited to talk about this with our guest. But I do think that there are patients who prefer an oral medication. That highest dose was bid dosing. I think that's probably a little bit of a deal breaker. But they do have their phase three data or phase three trial. They're doing 200Q day and their, their top line results have not come out in the literature, but they've come out in press and it's about 74% IGA01, about 65 Pazi90. That's what's been released top line. So, you know, kind of pretty good consistency, you know, good safety. If you're like what's the Achilles heel with the oral dosing you have? They are through the studies, it was done on sort of in a fasted state. So like 30 minutes before, like in the morning, 30 minutes before you eat. It depends. Like is that a deal breaker for most people? And it's not like you know it like you explode if you have it on. Just means you probably have a little bit more bioavail, a little bit less.

[D]

That would be a horrible side.

[A]

That'd be a horrible gremlins. Don't get them, don't feed them after midnight.

[D]

You need a TB test, you need a TB test, you might explode and you may get an infection. Like what was that second one, the tb.

[B]

So I, I, you know, I think for patients who want Biologic like you know, safety and but want an oral medication and want, you know what is pretty darn good efficacy. I mean, you know, it's not like Cosentix does not meet Skyrizi's Pazi 100 results. But like all of us have patients on Cosentix who are clear and happy so. Or alumia. Same so. All right on that one.

[A]

Okay. All right, we're gonna move on to our second article. That one is mine. So here we're gonna talk about the Vitamma atopic dermatitis studies. So Tapitarov cream 1% once daily sediment efficacy in the treatment of severe, moderate severe atopic dermatitis and adults and kids down to two years of age in the pivotal phase three during trials. Key takeaway here at eight weeks, about 45% of people got to IJ01 and then on placebo it was only about 15%. So really good efficacy. You know, here are the interesting things. So first the, you know, I would like to compare it to Opzelura's efficacy. So I am a believer that you generally can compare phase three efficacy results and they're pretty predictive. But Opzelura's trials were with mild to moderate atopic dermatitis. And we know that the more mild AD is, the more responsive it is to therapy that's been published. So we can't really compare compared very well to Opzelura's data. You know, the other things that are interesting here it is approved onto age two right out of the get go. I think this will be a great, I think it'll be a. I don't say great. A really easy drug to talk to parents about because it's a naturally derived molecule. Literally. Tapineroff comes from worm poop. That is where they discovered to pin her off. And there's next to, I mean there's essentially zero systemic absorption. So there'll be no box warnings. It's very well tolerated, it doesn't sting or burn in anybody and it works well. So this is the first drug we're going to have in little kids that doesn't have any baggage. Right now it's got the folliculitis 10% but other than that, no baggage. Right. It's not like you Chrysa that burns and stings. It works better than Eucrisa that It's not like TCIs that sting and have a box warning. It's not like Opsalura that's got a box warning. So it's got like, it's effective, it's fast and there's no baggage. It really to me is an interesting thing to see how much if this is going to change pediatric AD in the same way that Obsolera changed adult ad.

[B]

Do you like it because you like contact dermatitis so much and just kind of be like another business revenue stream?

[A]

So there was no contact dermatitis in the atopic dermatitis trials. And so the.

[B]

There was some.

[A]

No, there was not. It was only in psoriasis. And they. It's believed that that's because Vitama normalizes cytokine levels. And so if you've got elevated IL17 and you drop it, you get a little bit of rebound of IL13, IL4th2 and so you can get a little dermatitis. Same thing happens whenever you bring IL13 down. You get a little rebound probably of IL17. But it doesn't last long enough to start to see psoriasis stuff. Now. That's the theory. Who knows? The folliculitis is definitely still there. I did this trial, had a lot of kids and I would say, yeah, it was about 1 in. About 1 in 10. I think it's a little harder in AD because AD, like if new spots show up, that could just be ad. Right. Whereas in psoriasis, new spots don't usually show up. So you knew that it was deflaculitis. But one of the. I'm excited to talk to Dr. Feldman about this drug because it's the idea to me of how much of the benefit is just going to be that from a compliance perspective, put this cream on wherever your kid has eczema, whenever they have eczema, versus like, well, don't use this steroid there. Don't use that steroid here. Don't use it longer than this. Moisturize three times a day, take two baths. Like is it, is it more than just the efficacy of the drug? Right. And that's going to be interesting. So you guys did fairly straightforward here one here. I think you guys got comments.

[B]

So how do you think this is going to compare to Zoreeve? So most recent Zoriv data are out. Right. So this was like 45. And I think it had a, an IGA response, right?

[A]

Yes.

[B]

With. To pinner off and with Zoriv it's like 35ish percent. Right. So do you think that's going to be meaningfully different and you know, or is this going to be like, you know. Well, there's, there's kind of like not a lot to worry about. You don't have the folliculitis. You know, do you think that there's going to be the spin of like is this is, I mean this is a novel mechanism of action with tipinor off. Right. This is sort of this aryl hydrocarbon receptor agonism. You know, you can sort of, you could say it's worm poop, but you could also say, oh, it's sort of like the same pathway as dioxin too. Right. So we don't know a ton about this pathway to say it's 100% as safe as rubbing worms on your skin.

[A]

Yeah, it's a fascinating question. So I don't know how I think peds derms will like Zoriv better because it's a known moa. Right. It's basically if you're a peds derm, you can think of, you can think of Zoriv as more effective Eucrisa that doesn't burn. Right. And they really like you Chrysa or I don't think they really like you Chrysa, but they like safety of it. My guess is that adult derms will use more fatama because they're less sort of safety. They're still safety concern, but not as much as peeds terms. That would be my guess as to what's gonna happen in the market. I don't think we'll ever see a head to head of the two drugs unless somebody does it. Like a small, you know, 20 people on one, 20 people on the other, but neither company's ever gonna pay for it. So it's an interesting question. Like I don't, I suspect, I think based on the data that Vitama is a more effective drug but. Right. It's got the folliculitis, it's got a new mechanism. Yeah. I could see it going either way because they're going either way. All right.

[D]

You said ops they would change the same way Opzel or changed adult atopic term. Are you blown away by opzel or adult atopic?

[A]

Absolutely. I think it is as close as we will ever get. So. Right. They've got pretty good data that the anti itch effect happens in 15 minutes. And my real world experience with it is mirrors the trials which the trials say with as needed use, 75% of people are clear, almost clear long term.

[D]

And that just I have not had like I haven't been blown away by it. Like it's not like people are coming back like oh my gosh, that drug was the best thing I ever used. I mean I'VE had people come back that are like, yeah, you know, it really hard to get number one.

[A]

Yeah.

[D]

So it took me forever. And, and you know, they, it's like, yeah, I'll just use my hydrocortisone. I don't, I don't use it that much.

[B]

I love, I love itch relief in 15 minutes. Not counting the two weeks it took you to actually. 15 minutes.

[D]

Yeah, my eczema just went away by the time I got it.

[A]

So I truly think of it as clobatism without having to worry about like all the other stuff. But I, yeah, I'm, I'm biased towards all new pharmaceuticals, so, you know, take everything I say with a grain of salt. All right, let's go on to our third article. Dr. Patton.

[D]

Yeah. I went back a few years. 2022, American Journal of Clinical Dermatology. Steingold et al. Efficacy and safety of a fixed dose Clindamycin phosphate benzoyl peroxide, Adapalene gel for moderate to severe acne. Randomized phase two study. The first triple combination drug. So this is Cab Trio. Right. Dr. Feldman had a recent publication about Cab Trio. Four weeks. We'll get into that with him. I just kind of went back to the original like, like I haven't prescribed this. I don't think I've had a patient come in and say, I love my Cab Trio. Can I get some more? So I just wanted to go to the original study, kind of look what it looked like, you know, it has the three things. BPO and Adapalene are micronized and it's a gel so it distributes more evenly on the skin. All this information was in the intro. Sounded good to me. Patients had moderate to severe acne. Severe acne, they had to have, you know, so many inflammatory, non inflammatory lesions. They couldn't have bad nodular acne. And they were randomized to either get the triple cream or like the dyads, you know, just two of the three. Clinda, BPO versus BPO, Adapalene versus Adapalene. Clinda or vehicle. About 150 patients in each arm. Multi center, double blind, blah, blah, blah. So treatment table 2 shows the treatment success. So that's. This is at least a 2 point improvement in EGSS. What was it? Evaluator, Global severity score. And being either clear, almost clear at 12 weeks. 50% for cab trio and the dyads it was like in the 30s. So this drug is awesome. You go to figure two improvements. Inflammatory acne, non inflammatory lesions. But this is where it's Kind of like what? This isn't that good. So what do you want to say? The numbers. Let's say patients started with 50 inflammatory papillos on their face at 12 weeks, if they use cab trio they'd have about 12 lesions if my math is right. And if they use Clinda BPO, which is like the worst dyad, they would have 18. So a kid who uses Cab Trio is not going to look at the kid who use a diet and be like my acne is way better than that kid. They'd be like, that kid has acne just like I do. Non inflammatory lesions were better. And then what killed me about this trial was the quality of life measures. Right. That's all that matters for acne. Like is the patient happy with their acne with within some patients are like exploding. Yeah, exactly. So as Cab Trio statistically significantly better at anything else in quality of life measures. Like I don't think it was because the authors specifically say improvements in acne quality of life scores at week 12 were numerically greater. That's the word that you use when it's not statistically significantly greater. Right, True. So it's not, it's not any better in terms of what matters for acne. It's not any better than any of the dyads. And so like why is it being sold to us this way? And you know, I don't want to get into industry funded. You know, they hired scientific writers that are acknowledged that actually aren't authors on the paper.

[B]

Every medical, every drug is industry funded pretty much. And everybody has hires writers. Right. I mean don't put it in money. I would hire writers to write all my papers.

[D]

This is an advertisement.

[A]

That's what we have residents for.

[D]

This is an advertisement by the company that's masquerading itself as a, you know, like an independent scientific inquiry.

[A]

But it's an ad that's every phase three. That's exactly what you're saying.

[D]

It's all a problem. Like don't do it this way.

[A]

I actually would think it's a. You, you know, you were saying this and I was thinking about it. It does make a to sense that companies should just put all of their date. Like I should be able to go to every drug's website.

[D]

Right.

[A]

And, and like the meeting almost the raw data be there and like be able to, to do go through that instead of putting it in journals.

[D]

Right? That's it. So have a website. Here's a link to our study. It was fda. Like it's still that doesn't make it any worse of a study. FDA will still approve it. They have to, to, to meet all those requirements. Here's our raw data. You can have access to that. The drug companies don't do that either. You can't see the raw data and they sell it to you in the, in the most. It's deceptive, right?

[A]

But then they, but then the JAD wouldn't have anybody advertising.

[D]

And I agree. It's all a problem, you know, All a problem. Now is it? Like, do I really care? I mean, I don't really care. And actually cab trios, like, it's kind of a nice drug if you think about it, right?

[A]

I mean, well, but in acne, it's hard to. We've got a drug that gets 80% of people 100% clear for the rest of their life, right? My daughter's got three pimples and you're going on Accutane. And like, it's hard for me to understand why we even try and treat acne topically.

[D]

They have four patients and I would say all of them, I would have said there's this really good drug and you might be clear in four, five or six months. Like, this is the thing, they say, oh, acne requires long term treatment. Like, no, it doesn't. And if I was an author on this, I would say, let's not say that because that's not true. They say one part, like, why even add clinda in here? Like, topical antibiotics don't make any sense to me. Bacterial resistance, I know it's lower with bpo, but it could be zero with not adding clinda. And they have this, they say, well, adding clinda increases the antibacterial activity of BPO or something. How it increases it. It. And then they have a reference and that's not what that reference says. Like, I looked at the study for the reference. I'm like, it says nowhere in here that clinda adds to the antibacterial of bpo. And I used AI, even Matt, because, you know, it's better than us. I'm like, AI, does this paper actually show that it increases antibacterial activity of bpo? And they're like, no, I, like, I can't see that. So it's, it's, it's all very selective. It's, it's deceptive. I don't like it. I don't like these studies.

[A]

I don't like them so far. Takeaway is we don't let Patton review any more pharma articles that Exactly. That's how we handle this kind of dissent.

[B]

You're limited to case reports.

[D]

It's not going to. It's not going to.

[A]

Well, let's, let's move on and, and bring our guest on. So, as I mentioned at the beginning here, I'm so excited to have Dr. Ste Feldman on. So I. One of the lectures I remember very clearly from early in my career was a Pennsylvania Academy of Dermatology meeting where I saw Dr. Feldman lecturing about psoriasis. And he taught me some of the stuff that I still use to this day and think about him when I use it, that I touch every patient with. I touch their psoriasis so they know I don't think they're gross and that I don't think that they're contagious or whatever. I sit down with people, I talk to them like a normal whatever. But, but I had just learned so much from Dr. Feldman over the years about compliance or adherence. I'm so excited to have him on. So, Steve, great to have you here. And I am actually, we're going to start by kind of letting Dr. Patton sort of ask some about this new four week cab trio article that just came out. But I guess before we get to that, any comments on our discussion up till now? Any thoughts?

[C]

Yes. First of all, thank you so much for having me. Your discussion so far has been highly entertaining. And what I really appreciate the most is that you chose three articles that are all about patient adherence.

[B]

That's why we did it.

[A]

That's literally. We were like. We would have Steve Feldman on. We're going to have. So let's get into it. Patton, go ahead.

[D]

Yeah. So Steve, you had one article, it was long time ago, but it was basically how compliant. I think it was an acne study. And it was like one single cream. And basically compliance was. I mean, it was just horrific. Right? I mean, patients do not use their acne cream.

[C]

Are you serious?

[D]

That wouldn't blow me away. But the number was so terrible. I mean, my kids have acne and they're actually okay. I was, I was very surprised at that number.

[A]

It was zero. That was the. That's why you were surprised. It was not a single per. It was the one where he had the little cap on the electronic cap. You measured it. Not a single person used it 80% of the time. Not one.

[D]

So something like Cab Trio with, with what I think is a minute, clinically minimal difference. But because it's three and one, you know, it's once a day. But you showed Compliance really wasn't that good for if you're just using even something once a day. Do you think cab trio makes a big difference in that?

[C]

Well, big is. Is hard to define. I mean, I think it makes a difference, sure. You know, you mentioned that there was not a big difference if they used, you know, the triple versus using the dyad. Be very careful with your language. There's very little. There was difference between the group assigned to use the triple versus the group assigned to use the dyad. You know, when residents say, oh, the patient is using xyz, I'm like, are you in the room with them watching? You know, if not, then you should say, they say they're using. They claim they're using. Allegedly. They're on. You know, they're using X, Y, and Z. Okay.

[A]

Yeah.

[C]

And this. This theme runs through all three of these. These papers, because you go, well, this oral IL23 blocker is not as effective as injectable IL23 blockers. Well, what is the mechanism for that? If you're blocking IL23, they should work the same. Well, maybe they're not taking all the pills. I know this is shocking, but patients aren't always fully adherent to their treatments.

[B]

So do you think they're better in trials, though? Like, because we did this, and it's like they had, like a. They had, like, a card and, you know, like, they had the blister packs. Do you think that that helps, or do you think they're like, oh, I got my study appointment, like, pop, pop, pop, pop. There you go.

[C]

Well, they both. Yeah, now that you mentioned it. The pop, pop, pop. I'm sure that's happening, but I think blister packs are much better, and they've been proven much better. Because in the 1960s, birth control pills worked okay, but not great. They didn't change the chemistry. They just changed the packaging to tell you what pill to take, what day, and they became dramatically more effective. But the. Why are we. Nothing should be packaged in a bottle, especially a beige bottle that's designed to blend into the. It's as though somebody was intentionally trying to make people. Look, I would make pink bottles and blue bottles. Laura, you know who the pink bottles are for, right?

[B]

What are. Those are. No. Oh, that's Pep Bismol.

[C]

I mean, I put triamcinolone in pink bottles and blue bottles. The blue bottles, Tim, would be for the boys. You are so not woke. No, for whoever wants them.

[D]

What?

[A]

Oh.

[D]

That was a trick question. That was.

[C]

Yeah, it was.

[A]

It was a trick Question.

[B]

So I am politically sensitive, which is why I said Pepto Bismill.

[D]

That was a better answer.

[C]

So. But also, in the trials, they're bringing patients back at weeks 1, 2, 4, 6, 8, 12. And those visits dramatically increase in here. And based on what Tim has said about the poor response of his patients to, you know, topical opzelura to the acne medicines, I'm pretty sure he's not bringing the patients back at weeks 1, 2, 4, 6. He's probably telling people, here, use this. See, in three months, do you know what would happen if a piano teacher said, here's your sheet music, practice every day. I'm not going to have weekly lessons with you. I'll just see you at the recital in three months. That recital is going to sound abysmal. And dermatologists are worse than that. You know, dermatologists would be like a piano teacher saying, here's a prescription for some sheet music. Take this to the sheet music store. I have no idea what it's going to cost you. I want you to practice this sheet music every day. Now, if you do, you may get rashes, diarrhea, possibly a serious infection, but I want you to practice every day. I will see you at the recital in three months. If the recital doesn't sound good, which it often doesn't sound, I will give you a second and possibly a third musical instrument to practice at the same time.

[A]

So, Steve, you're reminding me of something. So, years ago, you and I were lecturing together, and I was going on about how great CeraVe is, and it's like a miracle, blah, blah, blah. And you're like, matt, do you think maybe the reason you think CeraVe works so well is because you're telling your patients, oh, my God, this is a miracle. It's the blah. And I actually took, like, first I was like, you might be right, but then I took that home, and now. So here's my spiel. Whenever I'm doing opzelura for a patient, this is like a miracle. You're gonna put it on, and your eczema is going to be better right away. It's completely safe. And you know what? This stuff is so good. It's like a $2,000 a tube. But I'm going to be able to get it for you cheaper. But it's. It's worth it. It's so good. Whereas I bet Patins is more like this drug. It's no better than anything else.

[D]

It's.

[A]

It's too expensive. They shouldn't have made it.

[D]

Well, Wait a minute. It may not be, it may not be any more effective than Triumph Cinolone. I think Opsolor does have like a head to head with, with tack study. And it, it didn't really blow tack away.

[C]

It was more effective than the tack in that head.

[A]

It was twice as effective, depending on the.

[C]

Here's the problem, Tim. You're not giving Opsalura first, you're giving Triamcin alone first.

[D]

Yeah.

[C]

And when you do, all the people who do well on it, all the adherent patients, they do great and they stay on it. All the non adherent patients who don't put their topicals on are the only ones you're prescribing the Opzelura to. So you have selected for non adherent patients when you're treating them with opzelura. And despite that, it still works some, which means it's probably dramatically effective. It's kind of like tar in psoriasis, which by the way, same miracles of actions to Pinorov. The fact that it works at all proves that it's extraordinarily effective because it is so messy. God knows people can't put it on.

[A]

I love it when somebody outsmarts Patton. Right. That it's the. You selected for the non compliant people. Oh, that's good.

[C]

Without question. Yeah.

[A]

I mean, Steve, do you think the real, like, you're been working on adherence for decades, do you think the answer is we're going to figure out how to get people to be adherent or do you think the answer is we just need to come up with drugs that are idiot proof? Give yourself a shot once every three months, like, and that's it, like we should. Is it even worth trying to get people to be more adherent?

[C]

Was published a study on the long term adherence to topical fluocinide for psoriasis. I couldn't use Clobatazol because I wanted people to be able to use it every. I want to be able to tell people to use it every day. The adherence in the long run was so abysmal that the British Journal of Dermatology let me put the word abysmal in the title of the paper. Yeah, I didn't want the word abysmal on the paper. I'm like, I'll go to the Brits, they'll let me put it in there. So I think you can get people to use the medicines. I think you can, but you have to be willing to do stuff. Now, for example, you can use for a patient who has resistant atopic dermatitis what you can do is bring them to the office for phototherapy treatments on a daily basis and explain to them to bring their triumphant ointment so that you can apply it to their ointment, you know, to their. To their dermatitis every day so that the light will penetrate better. Because as you know it, you know, the scale reflects light. And if you just put some of that triumphant ointment on, the light will penetrate better. And if you don't have a light box, you just use a woods lamp for this. Because the point is. The point is you're going to make sure that that topple gets on them every day. Now, it doesn't take a lot to Tim's and right. You probably don't need opsolure because if you did put the triamcinolone on, they would clear up. Because y' all have. I know all three of you have probably admitted patients to the hospital with resistant atopic dermatitis. And you put triamcinolone on them in the hospital and they cleared up in two to three days. I mean, from total body, like henified dermatitis, to clear in three days with triamcinolone. It's not that you're taking them away from the dust mites at home, which is what I was told when I was arrested. You're taking away from the stress of the home environment. So all you gotta do is get people to start on the drug, use it really well for three days. So you could, if you give them an office visit in three days, it would be like a dentist telling you, I'm really worried about your gums. I want you to floss every day. I'm gonna see you back here in three days. People who've never flossed before will floss those three days. And then if you don't want to bring them back, you tell them, here's my cell phone number. You call me in three days. Makes a dramatic impact on their use of the medicine. I've been theorizing that every time my electronic medical record sees that I write a new prescription for the patient, it will send the patient a deep fake of me, my face, my voice talking to them, saying, hey, we started you on this medicine. I'm going to call you back. I'm going to come back to you in three days, you know, to find out how you're doing. And then the. They're thinking they're going to talk to me in three days. But it will be the deep fake, it will be electrons. It will cost nothing to Create this sense of accountability that drives people's behavior, you know?

[D]

So for acne, though, I. I want to say if, like, the presence of acne and how much it bothers you, that needs to be the driver. If you come back to me in three months and we're honest and said, I didn't really, I wasn't great about using this. That's not my problem. Like, I. Like, we don't have. We have very little time as it is. I think that becomes so hard when, you know, I take a medication, I have blood pressure, I take it every day. If I went back in three months to my doc and was like, ah, I'm not really doing it, I wouldn't say to her, like, wow, you need to help me take it more. I would say, I need to take this.

[A]

So wait, Steve, I don't much to say about this. Do the patients think they're using it? Right? So there's a difference between, they're lying. I'm not really using it, but I'm going to pretend I am. And I put it on every day. But really, they didn't put it on every day. They just don't know, like, which of the two. Because that gets to Patton's question. If it's that they think they're using it, then I feel like it's more on us. If they know they're not using it, then I kind of agree with them that it's more on them.

[C]

Well, it's clearly on us. Dermatologist Danny Berg once told me about this wisdom from a Vietnamese Buddhist monk named Thich Nhat Hanh who said, if the lettuce is not growing, well, you don't blame the lettuce. All right?

[D]

Lettuce can't choose.

[C]

You know, it's all your fault, Tim, for telling them to come back in three months. If you have a student who's at the top of their medical school class, who's desperate to get a dermatology residency, who is as bright and industrious as anybody on the planet, would you tell them who comes to work with you over the summer and wants to publish? Would you tell them, here's your project. Work on this every day. I'll meet with you again at the end of the summer. No, it would be ridiculous. You would have weekly lab meetings with them that would make them work. I think you're right, Matt, that they don't even realize how little they're using it. But the idea that they're bothered by their disease is going to make them work make them use the medicine is simply wrong. And best example of this is a story I got to tell when the dean invited me to speak to all the big donors of our medical center and I'd given my adherence doc, and the dean, who's a hypertension doc, said, you know, I'm really shocked your patients aren't using the medicine. Doesn't make sense to me. I take care of diabetes and hypertension, silent diseases. But you're taking care of diseases where the patients are itching or in pain and they see their lesions, I would think they'd be adhered to the treatment. And I said to the dean, in medical school, they taught me nothing about adherence. I use this book, Goodman and Gilman for pharmacology. Massive textbooks, really thin sheets of paper covered everything that affected drugs except for the three most important things, which is whether they use it, whether they use it, and whether they use it. But I was at the va, I admitted a patient with a sexually transmitted disease. And I'm reading everything I can find about, you know, sexually transmitted diseases because I'm going to get pimped at Duke the next morning on rounds. And I read that if you have gonorrhea, you could cure it by taking a pill daily for seven days. That's all you gotta do. You take the antibiotic pill for seven days and you're cured. But we do not treat people that way. We inject them with penicillin because you can't count on people taking a pill consistently for just seven days for gonorrhea. Now, I know psoriasis bad. I know that atopic hormone toxins is horrible, but if I had gonorrhea, if I had this painful cup dripping out.

[A]

Okay, I would think that would bother me.

[C]

I would think that that would affect me socially in my interactions with, you know, people. But they won't take a pill. The stuff we ask them to do, the stuff you're asking your acne patient to do for three months, they're not.

[D]

You know, I just realized, like, accu. Maybe that's why Accutane works so well. Like, to me, I was like, accutane works because patients are motivated and they want to take it. But you have to see those patients every month because of the whole I pledge thing. And so now I'm realizing maybe that's it.

[C]

Yeah, yeah, that's a part of it. Accutane works really well. It's a for giving drug. If you miss a dose, probably doesn't matter because the half life is so long and. But the next time you see an Accutane patient, what I would like you to do is simply ask them if they're taking it regularly. But this is how I want you to phrase the question, okay? Sometimes we get gaps between these monthly visits. Do you have enough extra pills on hand to carry you through those gaps? Now, if they say yes, that means they are not taking it regular.

[A]

Yeah, and they're in blister packs. That's the other part of it. Steve. It has been a ball talking about compliance, and I think we're ready to move on to what is universally everyone's favorite segment of the show, patent trivia. Patton, what do you got for us this week?

[D]

Okay, so pay attention. This is. This is harder than prescribing an acne regimen. All right, the title of this trivia, it's called Biosimilars or Science Fiction. I have seven names in front of me here. It's either a biosimilar or a name taken from science fiction. So I'm going to say the name, and you either say science fiction if you think it's from science fiction, and if you answer it correctly, then it's over. You win. You can't answer more than once, so you can't, like, give two answers. You can't go science fiction or whatever. Now, if you think it's a biosimilar, you have to tell me what it is. A biosimilar to either, like, the first branded that came out or the generic.

[B]

Okay.

[A]

Okay. All right. All right.

[D]

Makes sense.

[A]

Yeah.

[D]

You only get. You only get one answer. You can't keep guessing on this one.

[A]

Okay, so we're gonna. So it's one person at a time. So we'll start.

[D]

No, no, no, no, no. All three, but.

[A]

Okay.

[D]

You either say science fiction, or you name the biosimilar that it is a biosimilar to. You know what I mean?

[A]

Yep. So do we say biosimilar, or do we have to say, like, you say.

[D]

Yeah, so you say Zola or whatever. Right.

[A]

All right, all right.

[D]

Okay, ready? First one. We got seven of these. It should go pretty quickly so that we should do this. First one. Simlandi.

[C]

Biosimilar.

[D]

No. What's it? A biosimilar, too. You have to. You have to name the drug or.

[C]

Adalimum.

[D]

Yep, got it. So that's how you answer. You would answer Adalimumab.

[B]

Or Humira.

[D]

Or Humira. You're allowed to use brand names.

[A]

Feldman, one. Cyrus. Fair, zero.

[D]

Yeah. Second. Avsola.

[C]

It's a Biosimilar of. But what is it?

[A]

No Ferris, one. Feldman, one. Oh, they've got a North Carolina showdown here.

[D]

All right.

[A]

Are you guys Tobacco Road or is that Unc and Duke?

[B]

No, I don't know. I haven't been here.

[A]

There's a Tobacco Road rivalry. Okay.

[D]

Third one, Omelas.

[A]

Science fiction.

[B]

Science fiction.

[D]

It is. Science fiction. The name of a fictional city in a short story. The Ones who Walk Away from Omelas by Ursula Le Guin.

[A]

They're all tied up. One, one, one.

[D]

Reabni.

[A]

Science fiction.

[B]

No Ramicade. No Ritux Alaki.

[A]

You only got one guess.

[C]

Yeah, I've not heard of that one.

[D]

No, no guess can't hurt. Doesn't. You know, no points.

[C]

What's the name of it again?

[D]

Reabni.

[C]

Yeah. Rituxima.

[D]

Yes, Rituxim. That kind of goats. Yeah, yeah, yeah.

[A]

Better to be lucky than good sometimes.

[D]

All right, number five. Irulon.

[A]

That's definitely science fiction. That's the name of an elf in something.

[D]

It's the name of a princess from Dune. Okay, okay, number six. I. Muldosa.

[A]

Science fiction.

[D]

No.

[A]

This one's.

[D]

It got approved at the end of last year.

[B]

Stelara.

[A]

Yes, it's 2, 2, 2 going into the seventh.

[B]

Yeah. You've only won on science fiction. I'm going to point that out. I know more medicine and you know more.

[D]

If you said science fiction right away for every question, you'd have the same score you have right now. All right, last and final two. Two, two. This is good. You fly, Ma.

[A]

I'm going science fiction.

[D]

No.

[A]

That sounds like science fiction. Oh, look at it.

[D]

The.

[A]

The UNC Wake Forest showdown. Neither one of the. There's a lot.

[D]

Right?

[A]

There's a lot of bragging rights riding on this.

[C]

I'll go with an embryo biosimilar.

[D]

No, it's all of you. Ferris. All the time of the world. What do you got?

[B]

I'm gonna go Stelara again.

[D]

It's Huber. It's a Adalimumab biosimilar.

[B]

Oh, I thought I knew all of those. All right. I was.

[D]

I was looking three way tie.

[B]

I. I'm waiting for Julio to come out. That's my favorite name of a Humira.

[D]

The Humira ones are good. The ones that are coming out for Stellara. I mean, they're. They're like. Every single one sounds like a science fiction character. It's. It's awesome.

[A]

Yeah.

[D]

All right. That was fun, guys. It's a three way tie. The first ever in the history of the podcast of Derms on Drugs.

[A]

It's true. Right, Steve? Dr. Feldman, thank you for joining us today. This has been a very, very fun episode. And I want to thank all of our listeners for joining us this week. If you got questions, comments, ideas for topics we should cover on the show, shoot us an email @questionsrms on drugs.com Again, that's questionsrms on drugs.com I hope you learned a few things. Hope you laughed once or twice. But mostly, I hope you're going to join us next week. Until then, I'm Matt Cyrus.

[D]

I'm Tim Patton.

[B]

And I'm Laura Farris. And we are Derms on Drugs.