Acne Vulgaris: What New Treatment Options Are Available?

Dr. Greenberg:
Acne vulgaris is a common dermatologic condition with a variety of treatment options available, but due to its multifactorial pathogenesis and the limitations of current therapies, evolving treatments and management guidelines are needed.  So what new therapies are available?  And are they showing promise of efficacy? 

Welcome to DermConsult on ReachMD.  I'm Dr. Michael Greenberg.  And joining me today is Dr. Arash Mostaghimi, Assistant Professor of Medicine at Harvard Medical School and Director of Dermatology Inpatient Services at Brigham and Women's Hospital. 

Arash, welcome to the program today. 

Dr. Mostaghimi:
Michael, thanks for having me. 

Dr. Greenberg:
Oh, it's a pleasure.  All right.  So look, Arash, before we jump into new therapy options, can you explain the pitfalls of current treatments that you're concerned about? 

Dr. Mostaghimi:
So like everything in our lives, we want more, we want better, we want cheaper, and that extends to acne treatment as well.  So when our patients come to us, the more arrows we have in our quiver the better off we'll be.  So acne is a very personal disease.  Ninety percent of people get it over their life.  You know, we're happy when the patient is happy, and the more roads we have towards achieving that happiness I think the better off we are.  And from a medical standpoint, what we're really looking at is reducing antibiotic use, reducing systemic therapies, and really looking at sustainable topical treatments that patients could use over the long term. 

Dr. Greenberg:
Yeah, I think every dermatologist listening has a bunch of patients that say, "Oh, give me something else.  It's not doing what I want."  Are we heading in that direction?  Are we talking about some real changes here? 

Dr. Mostaghimi:
We're talking about both.  I think one of the challenges we've had in acne treatment has been that the latest and greatest is sometimes combining two things that we already have into one or changing something from a 1% formulation to a 1.2% formulation.  So while that stuff is still going on, the nice part is that we actually, over the last couple years, for the first time have 2 or 3 novel agents that I think have the potential to really change the way that we treat some of our patients. 

Dr. Greenberg:
Awesome.  Well let's take a look at some of the newer options available.  Let's start with clascoterone.  What's good about it?  And what problems with current treatments does it address? 

Dr. Mostaghimi:
So clascoterone is one of the new medications that I think is most exciting, and it's most exciting because it's the first drug in its class.  So the best way to think about clascoterone is that it is a topical analog with spironolactone.  It's not the same molecule.  It's not spironolactone.  It's a different agent, but it is an antiandrogen, binds the androgen receptors.  It's deactivated before it's absorbed into the body and gives us a way, finally, of treating hormonal acne with a topical. 

Dr. Greenberg:
My patients love topicals. They much prefer that to taking medication internally.  So what are the safety concerns with this medication? 

Dr. Mostaghimi:
So in contrast to spironolactone, it's a better choice for patients that may get dizzy with spironolactone or have menstrual issues with spironolactone or just, you know, don't want to be on a medication that impacts their hormones longer term.  From a safety standpoint, most of the stuff that they saw was a little bit of irritation, a little bit of redness on the skin, nothing particularly exciting.  There is some data from one study, a phase II study where they treated a large surface area, so they treated somebody's face, top of their chest, their shoulders, and the top of their back, and in those patients they found that about 7 percent of them had asymptomatic adrenal suppression. It's not something that has popped up anywhere else, so I think that if we use it on smaller surface areas, which is generally what we do with topical treatments, so far we don't have any particular safety concerns. 

Dr. Greenberg:
Okay. So is this just being studied, or is this available for us? 

Dr. Mostaghimi:
It's been studied. It's been FDA-approved. It's actually available, and hopefully, the pharmacy will have it, but it  should be more available throughout the course of the year.

Dr. Greenberg:
So let's change course a little bit and turn our attention to sarecycline. What can you tell us about it?  And why is it better than what we already have? 

Dr. Mostaghimi:
So the real concern that people have with use of tetracyclines in acne is microbial resistance.  Right?  So you have other gram-positives, some gram-negatives, some anaerobes that you are actively hitting with this medication that we are not intending to.  The concern is that over time this could lead to increased antibiotic resistance, not only within individuals but across a population.  And, Michael, as you may know, dermatologists prescribe the most number of antibiotics of any specialty, so we are really good at giving people long courses of antibiotics. 

So sarecycline is a tetracycline that is designed to fix that problem by basically being a really bad antibiotic.  It's a super narrow spectrum of action, so you don't get all the off-acne targets that you would get.  So the concern around antibiotic resistance is not supposed to exist with this medication, and you should be able to use it for longer periods of time and more safely. The second issue is unlike let's say, minocycline, which does cross that blood/brain barrier a bit and causes some central nervous system issues in folks, this one is really not supposed to do that.  So you can think of it really as a doxycycline that is, first, much more expensive than doxycycline, so you've got to be thoughtful about when you use it, but also potentially something that we may be able to use longer-term than doxycycline and with greater impunity. 

Dr. Greenberg:
So for those of you just tuning in, you're listening to DermConsult on ReachMD.  I'm Dr. Michael Greenberg, and today I'm speaking with Dr. Arash Mostaghimi about new acne therapies. 

Let's continue, Arash.  Let's talk about trifarotene, which is another topical retinoid.  So what's good about it?  And on the flipside, what's bad? 

Dr. Mostaghimi:
So trifarotene is a newest-generation retinoid, so you can kind of think of it in the same family as tretinoin and adapalene and those medications.  It is supposed to be a little bit more specific with the specific retinoid receptor that it attaches to.  You asked what is good about this.  I don't really know because I'm not sure that this will make that big of a difference for patients, and there hasn't really been a head-to-head comparison with other topical agents to understand whether this is better tolerated than, let's say a tretinoin or an adapalene, etc.  So if you look at this, both the efficacy and the side effect profile is actually very similar to any retinoid where you get redness and scaling and erythema, but it works pretty well for your acne.  So I think the jury is out on this one as to what its role is in acne therapeutics and where will it be and will it work when other retinoids, you know, didn't work, or will it be tolerable in a way that other retinoids are not.  I think we have a lot of option in this space, so this one is one that I'm figuring out where it fits in. 

Dr. Greenberg:
Now an important thing I want to talk about is the data on isotretinoin and suicide.  Can you discuss that for us? 

Dr. Mostaghimi:
So we did a study a couple years ago where we looked at all of the isotretinoin reports via iPLEDGE where patients either engaged in self-harm or suicide, really looking across psychiatric side effects.  That was published in JAMA Dermatology for those of you who want to take a closer look at it.  It was a hard study to do in large part because we lacked denominators, okay?  We don't know how many people are on iPLEDGE who were taking the medication at any given time.  But what was clear from this evaluation was that every year there are people who take isotretinoin who do commit suicide while they're on the medication.  Every year there are people who take isotretinoin who have mood impacts, depression, things along those lines. 

I think our conversation, Michael, as a field has been completely wrong.  We've been too focused on the idea as to whether or not the isotretinoin itself is causing this or whether this is something else, whether the patients were already depressed, whether acne already makes  you depressed.  I think we need to move on from that conversation and say that "Hey, as physicians, we're being thoughtful about who we're giving these medications to."  Right?  We're making sure they have the appropriate support that they need.  Isotretinoin is a profound net positive in society for the patients and for the people who are taking it.  It truly changes lives—right?—without any question.  Our job should be that "Hey, if I have to see this patient or talk to this patient every month, even if it's from the isotretinoin or it's not, how do we figure out a way where I can connect to patients and appropriately and safely screen them for depressive disorders, mood disorders, these types of things?"  Now we don't have the time, nor are we specifically trained for this, but our focus should be "Hey, if you're going to see a doctor every month and I'm that doctor, I don't care if you're upset because of the isotretinoin that I gave you or whether it is just your life.  How do I as a doctor, not just a dermatologist but as a physician, connect with you and provide you with the psychosocial support you need to get you the help to identify the problem you have and get you the support that you need?"  So I have this conversation with each of my patients where I bring it all out into the open. 

The nice part about younger kids today is that unlike the stigma that existed in our generations, Michael, with talking about mental health or asking somebody to go see a therapist or those things, the younger generations are much, much more amenable to this type of idea.  Mental health is much more of a normal thing to talk about.  The stigma is not eliminated but has been reduced.  I engage in that conversation, I open the door, and I talk about it every time even if they appear to be happy with the sense that they can tell me about it, and I can provide them with support. 

So the data is basically—Do people on isotretinoin commit suicide?  Yes.  Do they commit suicide because of the isotretinoin?  Who knows.  Is our goal as a group of dermatologists to try to provide every patient as much care as we can and provide them with the best mental health while we're tracking them through their treatment?  Absolutely.  And that should be our focus. 

Dr. Greenberg:
So finally, let's talk about spironolactone.  Tell me about its positives and its negatives. 

Dr. Mostaghimi:
So I love spironolactone.  I use it a lot.  I think the best thing about it is that it is a safe, nonantibiotic medication that you can take for an extended period of time, and if you tolerate it, you can basically take it for a long time, and it uniquely helps with hormonal acne.  And until the clascoterone that we just talked about, we didn't have anything else really in this category.  Maybe some of our oral contraceptives can do that and other things, but really, this kind of stood by itself so I love that component of it and I really enjoy how empowering it is to a lot of my patients. 

The challenges are there are some patients that get dehydrated, or some patients have menstrual irregularities with it.  Most of the symptoms that you get, the little bit of lightheadedness, the little bit of premenstrual-type symptoms with breast tenderness and things along those lines, usually if you can get them through the first couple of weeks with that, they can last on the medication.  And speaking of mood, very rarely you can get some depressive or mood-type side effects in these patients.  It's probably underreported, but keep that in mind if you're talking to patients and they bring this up.  But I think it's a great medication.  Its only downside really is there are some people that get upset about the impacting your hormones.  There's good long-term safety data.  Man, it's a super cheap medication otherwise, and you should use more of it. 

Dr. Greenberg:
So Arash, before we come to a close, are there any additional comments you want to share with our listeners? 

Dr. Mostaghimi:
Well, Michael, thanks again for having me.  I think the bottom line when you get new medications like this, it makes sense for individual physicians and practitioners to experiment on different patients, see what works, what doesn't work, get some feedback.  But I would encourage you that just because we have something new doesn't mean you have to use it, or it may not really have a role in your acne therapeutic portfolio.  So if there's a new drug or something that's substantially better tolerated, more efficacious, etc. than what exists, by all means, you go for it, right?  This is the exciting part about being in our field and engaging in science and advancing the field forward.  But just because you have something doesn't mean you have to use it.  And as it's come up a couple times in this conversation already, the economic consequence is not to your patient, right?  Even if they give you copay assistance, all that sort of stuff, the economic consequence to our system overall can be extremely high, so we need to be thoughtful stewards of those resources and just use them when we need to. 

Dr. Greenberg:
Those are some really important insights when it comes to new acne treatments, and I want to thank my guest, Dr. Arash Mostaghimi, for joining me today.  Arash, this was a total pleasure having you on the program today. 

Dr. Mostaghimi:
I appreciate it.  Thank you. 

Dr. Greenberg:
For ReachMD, I'm Dr. Michael Greenberg.  To access this episode and others from this series, visit ReachMD.com/DermConsult, where you can Be Part of the Knowledge.  And we thank you for listening.