Unscripted Podcast: Alopecia Areata: New Guidelines, New Treatments, and a New Standard of Care

Welcome to Unscripted, the AMCP podcast, a look inside managed care pharmacy.

Steve: Alopecia areata causes a profound psychosocial burden, derailing education, careers, and relationships. For years, patients were told nothing will help. 10 years ago, there were no FDA-approved treatments. Today there are three, and new clinical guidelines are changing how we think about severity, access, and timing.

This is Unscripted, the AMCP podcast. I'm Steve Kheloussi, and this episode is sponsored by AbbVie Inc. AbbVie, we find answers that make life better for patients and our world.

Joining me today is Dr. Arash Mostaghimi, associate professor of dermatology, vice chair of clinical trials and innovation, and director of the Dermatology Inpatient Service, and co-director of the Complex Medical Dermatology Fellowship at Brigham and Women's Hospital.

Welcome, Dr. Mostaghimi.

Arash: It's great to be back, Steve.

Steve: Yeah. So you point out that you've been on this podcast before. You've previously spoken with us about alopecia areata, and if any of our listeners haven't heard that episode, I encourage you to check that out. But I think it would be helpful to recap some of the background on alopecia areata.

So Dr. Mostaghimi, can you give us a bit of background on alopecia areata?

Arash: Yeah. So alopecia areata, the name gives you insight into what it is. Alopecia means hair loss, so we colloquially sometimes refer to alopecia areata as just alopecia. But every type of alopecia, every type of hair loss is alopecia.

Areata means round, so alopecia areata is characterized by these round circular patches of hair loss that you can get anywhere on your body most often the scalp. For the majority of patients they just get one to two spots. Maybe they go away, maybe they have another episode later in their life.

But in a subset of patients, they go on to have more extensive disease with loss of hair not only on the scalp, but potentially the eyebrows, eyelashes, beard, and the rest of body hair as well. So we have referred to patients that have total loss of their scalp hair as alopecia totalis, and total loss of all hair on their body as alopecia universalis.

Overall, about one to two percent of people will have an episode of this in their life. It's one of the most common conditions that affects humans.

Steve: That's really helpful background information. And so what treatments are available right now?

Arash: So the key thing driving alopecia areata is inflammation, and you can't see the inflammation in alopecia areata. It's under the skin. It's at the base of the root of the hair. But once that inflammation comes in the hair weakens and it falls out, and the residual inflammation keeps the hair from reentering the cycle to grow new hair. So when you see these round bald patches, they don't look red or inflamed, but they are inflammatory.

So the core treatments for alopecia areata are focused on reducing that inflammation. Right now, there are three FDA-approved medications. All of them are anti-inflammatory medications. All of them are JAK inhibitors impacting the JAK-STAT pathway and reducing the inflammation in the scalp and other parts of the body, allowing hair to grow back.

Steve: Excellent. Thank you. And are there any pipeline therapies that we have to look forward to?

Arash: So the next drug that looks like it's coming to market is upadacitinib. That's another JAK inhibitor. There are other drugs in development. So these three JAK inhibitors that are currently FDA approved, which are baricitinib, ritlecitinib, and deuruxolitinib, and then potentially a fourth one if upadacitinib is approved as well are all in the same class.

There are efforts to create targeted biologics that look at more specific cytokines. Those are a bit of a ways away from development. There's also some work on IL-2 agonists that can help increase regulatory T cells and perhaps grow hair as well. Those drugs are currently in phase two.

In addition, there are some efforts to treat more localized or smaller amounts of alopecia areata either with modified injectables or with topical agents. But for now, you know, we've been spoiled just about each of the last three years. In '21, '22, '23, we had FDA-approved medications for alopecia areata. Now we're going to get a fourth. There's probably going to be a little bit of a break before we get the next one.

Steve: Yeah, that makes sense. You can't have constant new medications reaching the market. But it seems like we've come a long way, and I think something that's really going to help is this new set of guidelines that have recently been published that you're one of the authors on.

And so it's really exciting to, to speak with one of the authors of the guidelines to kind of get a peek behind the curtain and, you know, try to understand what went into making the decisions that you made within these guidelines. So could you tell me a little bit about what's in these new guidelines?

Arash: Yeah. So let me walk you through the guidelines. The guidelines are meant for patients that have severe alopecia areata. So first off, in the clinical trials, that's defined as having a SALT score of above 50. SALT is the amount of hair loss that you have. So above 50% means that you've lost over 50% of your scalp hair.

SALT 100 means you've lost all your hair; SALT zero means that you've grown all of it back. So the lower the SALT score the better it is for the patient. In trials, the key requirement is SALT greater than 50, and then the outcome in trials is SALT less than 20. So if you basically go from having over 50% of your hair loss to having lost less than 20% or having over 80% of your scalp hair, that's considered the key outcome of success.

So in developing this, what's happened is that for a lot of payers, that SALT over 50 has become the key distinguisher of who has severe alopecia areata. And what we've identified with research is that while in general, patients that have more hair loss have more significant disease, it really doesn't capture the holistic experience of the patient. in fact, the 50% is somewhat of an arbitrary selection that was made in the, for the first trial and has kind of stuck in that way.

So the foundation of the new guidelines is using a consensus instrument called the AASC, the A-A-S-C. And this is an instrument created by a group of dermatologists and hair experts who really look to understand what are the main determinants of alopecia severity.

The core root of the AASC is the SALT score. So it begins with three different buckets of SALT score. SALT greater than 50, so similar to what we have as inclusions in trials right now; SALT 20 to 49; and then SALT zero to 19. The 20 to 49 is a moderate group, and the lower group is a mild group.

The key innovation of the AASC, though, is that it takes into consideration one of four additional factors, and if you have any of these factors, it will bump you up one notch. So if you have one of these factors, you may go from moderate to severe or from mild to moderate. And those factors are having rapidly progressive hair loss with a positive hair pull test being refractory to other treatments, having significant psychosocial impact on the patient, or having facial hair involvement, specifically eyebrows and eyelashes which makes your disease very visible.

So if you have one of those four factors, you could have SALT down to that 20 to 50 level, but be considered severe by these guidelines. So the first, I bring it up because the most important thing to start off with is that our definition of severe isn't exactly who's in the trial, isn't exactly who most insurances are covering right now, but I think reflects, what matters to patients, what impacts patients, and what direction we're going.

Steve: Wow, that's really interesting. I think that's going to have a profound impact on how payers are going to be looking at this. And we'll come back to the payer aspect of this in just a moment. But I really appreciate that these guidelines are highlighting that this is not just a cosmetic disease, right?

Arash: Yes. It's important to understand how much this impacts patients. So while some patients with alopecia areata may have itching or burning of the scalp, that really is the minority of patients. This really is a disease that impacts your ability to present yourself, your identification, the way that people look at you.

We've demonstrated that people themselves have decreased workplace productivity, that they have increased anxiety and depression. They are less likely to engage sexually with their partners. It really impacts every aspect of life.

And even for those patients who are not particularly impacted themselves, and that does occur that patients are comfortable with their with their hair, we've identified that those patients are subject to workplace bullying. They're subject to stigma from people in the community where they see them as being unclean or contagious or dirty less likely to want to give them a job, less likely to want to be their friend.

So this is really a disease that impacts all the aspects, not only of you individually psychosocially, but of somebody's interaction with society. And the AASC criteria allow us to look beyond a simple percentage of hair loss and really take into the account the overall impact on the patient.

Steve: That's fascinating. And I think that lines up with some other data that I've seen that, you know, patients are paying significant amounts out of their own pockets to, you know, conceal this disease, right? Wigs, hats, makeup, et cetera. This study found that patients are spending somewhere in the range of nearly $500 each, which is mostly not going to be covered by insurance.

So I think this is a really important aspect that we have to talk about because payers are very commonly going to look at clinical trials to determine how to define severe, you know, to ensure that coverage is as appropriate as possible within their coverage policies. And so, if the AASC incorporates all of these psychosocial outcomes, Is there a reason that we're not seeing it used in clinical studies, and do you think it will be?

Arash: For clinical studies, it's a little bit more challenging because the FDA often doesn't like, inclusion criteria that mix physical signs and symptoms with, emotional signs and symptoms.

But beyond that, nonetheless, the idea that as we learn more about a disease, we evolve what we consider to be severe or important and we understand better how it impacts patients is something that we've seen in dermatology across multiple indications, beginning with psoriasis, where when I was a resident, I am not going to date myself, by telling you when that was.

But when I was a resident, you basically had to be red head to toe with psoriasis to be considered severe enough to get a biologic. Now, you know, even with less than 10% of body surface area, or we understand if you have less than 1% body surface area on your palm, on your genitals, on your scalp, that you may qualify for these.

Similarly, we're seeing a move in atopic dermatitis towards treating patients with milder and milder, surface areas and less extent, physically apparent disease because we're understanding the impact on itch. We're understanding the impact on sleep. We're understanding the overall impact of this condition on their overall life and well-being.

Steve: Yeah, that's interesting. And so it'll be fascinating to watch how payers are going to follow up, you know, with these new guidelines. Are they going to adjust their policies away from just relying on SALT scores to determine severity, or are they also going to build in the AASC, if we're going to be seeing that, you know, come in on prior authorization requests and so forth?

And speaking of the payers what have you seen from managed care organizations? Are they considering the psychosocial impact of this disease when they are making those coverage decisions, or are we still seeing some gaps in coverage that need to be addressed there?

Arash: There still are gaps in coverage that some insurers will take that into account and people will write, you know, letters of support, and give other information to help, move through that prior authorization process. But it's not something that is, routinely done and really adds additional burden on both the patient and the, physician seeing that, that, that patient.

See, you know, I can get into the more of the specifics of the actual guidelines for you that I think will help understand how, payers will engage. So although we're starting with the AASC as the definition of severity, the key part about the guidelines is simultaneously what's in the guidelines and also what's excluded from the guidelines.

So the first-line treatment for alopecia areata, severe alopecia areata as, defined in these guidelines, is one of the FDA-approved JAK inhibitors. This should really move us away from needing step therapy, particularly with older medications such as cyclosporine or methotrexate or azathioprine. These are medications where the overall efficacy rates are below ten percent, maybe ten to fifteen percent. Each of the drugs I just mentioned is cheap, but it also has substantial side effect profiles with, large limitations on patients, large amounts of immunosuppression. And for each of them, we know that there's long-term toxicity and other challenges.

In contrast, while the JAK inhibitors do have a black box warning and require safety monitoring, we have really good data for their efficacy, which is substantially more than the drugs I just mentioned. We have long-term data for their maintenance of efficacy over time, and we have long-term safety data in the exact population that we're treating, these patients with alopecia areata.

One important note is that again, to clarify, these are FDA-approved JAK inhibitors for alopecia areata. So off-label use of a JAK inhibitor like tofacitinib, which does work in some patients with alopecia areata, it discouraged because we simply don't have the long-term data either for efficacy or safety to really be able to understand those drugs and understand the impact on patients.

So when I'm counseling a patient on a drug that's a long-term drug for a chronic disease, it really makes sense to take advantage of the large investment in long-term studies, registries, longitudinal evaluations that really allow us to speak with confidence about the long-term efficacy and safety of these medications.

There's another group of patients who are a little bit different, and these are the subgroup of patients, about a quarter of patients with alopecia areata that have atopic dermatitis as well, or something in the atopic dermatitis atopy family, which may include asthma, allergic rhinitis, things along those lines.

For those patients, we included dupilumab as a potential first-line drug as well with the caveat that the data for dupilumab is less than JAK inhibitors and that the efficacy of dupilumab seems to be less than JAK inhibitors, and that dupilumab really only seems to work in this population, not across the entire population of people with alopecia areata. But among those patients, if they would like to explore that, dupilumab off-label, in this case, because it's not approved for alopecia areata may be an appropriate alternative.

So those are the two key first-line agents that we talk about, primarily JAK inhibitors and then in a subset of population a subset of patients with alopecia who have atopy potentially dupilumab.

Steve: Yeah. That's a really helpful summary. And so it sounds like earlier treatment with the JAK inhibitors and some of those off-label options, but the non-biologic medications have really fallen out of favor.

One of the things that I think managed care pharmacists often think about is this idea of switching between these agents. Are they interchangeable? Can we put one on the formulary and not some of the others? And it leads to this idea of non-medical formulary switching where, you know, as certain medications' value is enhanced, whether that's through favorable pricing or, you know, some new data that comes out, whatever the case is there's this intention by the managed care organization to potentially switch patients who are stable on their current medication to their new preferred option.

And so, what is the role of non-medical formulary switching, within these guidelines?

Arash: So it's really important to understand the potential impact of disease flares on patients. Alopecia areata is really different than psoriasis or atopic dermatitis. So in atopic dermatitis or psoriasis, if your drug stops working or you get a flare, maybe you get itchy for a few days, maybe you get a little bit of arthritis, maybe you get a few plaques on your elbows or scalp or what have you.

In alopecia areata, even a short flare, a tiny flare may result in you losing hair. If you lose hair and you're somebody who has, let's say, shoulder-length hair, that flare doesn't just stop and then the next day you're back to normal or a week later you're back to normal. Once that hair falls out, if 18 inches of hair falls out, it's going to take you two years to grow back that hair and make you be able to look and express yourself the way that you want.

So flares are really much more consequential in alopecia areata for that reason, and also for the fact that these drugs work slowly relative to the atopic dermatitis and psoriasis medications.

So to get back to your question or your comment, it's okay for somebody to only have one drug on their formulary or a preferred drug on their formulary. I think at this point, we are not saying that one JAK inhibitor or one FDA-approved medication is superior to the others, right? But that said, non-medical switching is inappropriate for these patients. If you're on a drug and it's working and you're switching, this is not switching from one JAK inhibitor to another JAK inhibitor doesn't mean that the second medication is going to work. It may work better, it may work worse, you know, it may work exactly the same. But even if it is as good or better, even the act of switching, resets the clock, and that transition can lead to hair loss as well.

So, we can, look at this two different ways. If somebody is stable on their medication and doing well, they should be kept on that medication. They should not be switched off of it. If somebody is on a JAK inhibitor and they've tried it for six months and they're not getting the response that they need, it's totally fine to try a second JAK inhibitor. Just because they failed one doesn't mean that another one won't work. Even if on paper it has the same mechanism of action.

We don't know why this exactly happens. We think that there may be elements of metabolic differences or things like that that are similar. But that further investigation is required there. Both of these elements, most of these aspects that I'm talking about, the maintaining somebody on a drug that works and then switching to another JAK if the first one doesn't work these are also two aspects highlighted on our guidelines.

Steve: And you may not have an answer for this one, but is it appropriate to try a third and a fourth potentially, when it becomes available?

Arash: I think at a certain point the patient may fatigue because every time you switch, it takes a bit of time to see if the drug works or not. It takes several months. But certainly I think going from one to two to three to four, my hypothesis would be that as you move from one to the other, the more you try, the less likely they are to work. We know there are just some patients for whom JAK inhibitors are not the right treatment.

For some patients who have been on maybe one JAK or two and have had some regrowth but still haven't reached goal, one thing that we comment on in our guidelines is the use of adjunctive agents. Now, it's important to note these adjunctive agents are all off-label from an FDA standpoint, but they're commonly used in dermatology.

So they would include for the scalp intralesional steroids, a mainstay of treatment for alopecia areata. It would include oral minoxidil or topical minoxidil. For the eyebrows and eyelashes oral or topical minoxidil or bimatoprost. And then also for those areas you can use off-label topical JAK. So the same medications we're talking about or tofacitinib compounded into an ointment or gel and applied topically.

Steve: Interesting. Yeah and we certainly would love to hear more about these, you know, very hard to treat patients and all that, but unfortunately we're running low on time. So I want to wrap up with just one last question. This is the Unscripted podcast, so we like to ask, what is your one unscripted truth about alopecia areata? What is the most important take home message about something our audience may not know already?

Arash: So I'm going to cheat and use a compound sentence structure to get more than one point in, Steve. So-

Steve: That's fair. That's fair.

Arash: Alopecia areata is a disease with profound psychosocial impact that deserves to be treated if patients are impacted by their disease. And the best treatments for those at present are the FDA-approved medications that we have, the three JAK inhibitors, potentially, hopefully a fourth coming soon.

The bottom line though is that overall, while we've made huge strides in alopecia areata, and it's so exciting to have these new treatments, we are in the absolute early innings, both of identifying new and effective therapies for these patients, but also in making sure that we have the appropriate outcome measures and severity measures to really identify who are the patients that would benefit most from these treatments. It may be a totally different population than what a simple SALT score measures.

So in the same way that we saw that evolution, as I mentioned before, in atopic dermatitis and in psoriasis, over time what we're going to see is a similar reckoning in alopecia areata, where we want to make that the inclusion in clinical trials, the people that we're studying there, the people that insurances are covering and are committing to paying for these medications, that those align with the holistic evaluation of the patients that we see in our day-to-day clinics who would really benefit from those medications. Right now, those are not completely aligned. We have a lot of work to do, but I'm hoping the guidelines is a step in the right direction.

Steve: Fantastic. That was one very complex sentence. Yeah. So I'll accept it. That's a great point to end on. And thank you, Dr. Mostaghimi, for your time. This has been incredibly enlightening.

Arash: My pleasure. Thank you for having me.

Steve: And thank you so much to our audience for listening to this episode of Unscripted, the AMCP podcast. Please check out the new guidelines. They're a joint guideline from the National Alopecia Areata Foundation and the American Hair Research Society. This episode was sponsored by AbbVie Inc. For more information about AbbVie, go to abbvie.com.