Part 2: From Topicals to Biologics: Evolution of Treatment Options in Severe Alopecia Areata

In Part 2 of this expert-led video interview series, Dr Brittany Craiglow, Dr Brett King, and Dr Maryanne Senna discuss the evolving treatment landscape for severe alopecia areata (AA)—a once intractable autoimmune condition now seeing rapid innovation in therapy. With the emergence of FDA-approved JAK inhibitors such as baricitinib, ritlecitinib, and deuruxolitinib, dermatologists finally have powerful, targeted tools to offer patients meaningful hair regrowth.

The panel explores the clinical evolution from topicals and steroids to systemic immunomodulators, offering practical insights into patient selection, safety considerations, and treatment sequencing. Dr King highlights key data from pivotal trials that inform real-world treatment timelines, while Dr Senna shares her strategic use of oral minoxidil and intralesional steroids to enhance regrowth.

Importantly, the discussion also addresses how to navigate JAK inhibitor safety conversations, dose tapering, and common clinical challenges—such as slow responders or partial regrowth. For dermatologists seeking up-to-date, evidence-based strategies for managing moderate to severe AA, this conversation offers essential pearls and practice-changing guidance.

Brittany Craiglow, MD, is an associate professor adjunct - dermatology at Yale School of Medicine.

Brett King, MD, PHD, is a board-certified dermatologist specializing in hair loss disorders, vitiligo, and atopic dermatitis (eczema) in Connecticut.

Maryanne Makredes Senna, MD, is a board-certified dermatologist at Beth Israel Lahey Health, and assistant professor of dermatology at Harvard Medical School.

• Therapeutic Shift with JAK Inhibitors: Treatment for alopecia areata (AA) has advanced rapidly. Formerly reliant on corticosteroids, contact immunotherapy, and immunosuppressants, the current standard includes FDA-approved oral JAK inhibitors:
  • Baricitinib (approved 2022
  • Ritlecitinib (approved 2023
  • Deuruxolitinib (approved 2024

These therapies mark a shift toward targeted immunomodulation in AA.

• Patient Selection and Early Initiation:
  • JAK inhibitors are considered in patients with ≥25–30% scalp hair loss who fail conventional therapies or are predicted to progress.
  • Earlier intervention is associated with higher treatment response; delaying until complete hair loss or chronicity reduces efficacy.
• Baseline Screening Prior to Initiation:
  • Evaluate for contraindications including history of solid malignancy, cardiovascular events (MI, stroke), and serious infections.
  • AA patients are generally healthy, and most tolerate therapy well with appropriate screening.
• Managing Boxed Warning Discussions:
  • Patients are often informed about boxed warnings (e.g., cancer, MACE, VTE, infection) but lack context.
  • Clinicians should explain:
    • Boxed warnings stem from RA trials in older, comorbid populations (e.g., tofacitinib in >60 y/o with CV risk).
    • AA patients typically reflect a much lower risk profile.
    • Incidence of adverse events in AA patients on JAK inhibitors mirrors background population rates.
  • Emphasize informed, individualized risk-benefit assessments; most patients opt for treatment after contextual discussion.
• Treatment Duration and Monitoring:
  • Hair regrowth in AA follows a delayed trajectory compared to inflammatory dermatoses.
  • Clinical trial data support continuing JAK inhibitor therapy for 9–12 months before declaring treatment failure.
  • Early decisions (e.g., at 6 months) may miss one-third of eventual responders.
  • Regrowth of eyebrows/eyelashes by month 9 is a positive prognostic marker for future scalp response.
• Adjunctive Therapies to Enhance Regrowth:
  • Oral minoxidil is commonly co-prescribed to support density and speed of regrowth.
  • Intralesional corticosteroids or short courses of systemic steroids may be used in partial responders or plateaued cases.
  • Topical therapies, including topical JAK inhibitors, have not demonstrated efficacy and are not recommended.
• Switching Agents:
  • Lack of response on one JAK inhibitor does not preclude response to another.
  • Switching is reasonable after adequate trial duration if no meaningful regrowth occurs.
• Dose Tapering and Discontinuation:
  • Most patients require ongoing therapy; stopping or rapid tapering often leads to relapse.
  • If tapering is pursued (e.g., from 4 mg to 2 mg baricitinib), do so slowly, with ≥3-month intervals to monitor regrowth durability.
  • Relapse may lag behind dose reduction; abrupt changes risk irreversible setbacks for patients.
• Patient-Centered Approach:
  • Patients often express high motivation for treatment, even if small risks exist.
  • Shared decision-making and clear communication foster adherence and trust.
  • National Alopecia Areata Foundation resources, including educational videos, can support counseling, especially for risk-averse patients.

Dr Craiglow: Now we are going to move to talking about treatment, which is really exciting. We finally have some options for patients. So we're going to talk a little bit about the evolution of treatment, which has really evolved with our understanding of the pathophysiology of disease and some of the questions that come up in clinic. Because this is treating alopecia, it is often straightforward, but it also may not be, I think there is a lot of nuance in treating this disease. So maybe we'll talk about some kind of clinical scenarios where you have to really be thoughtful about your next step. So Brett, you talk often about where we used to be in alopecia and our understanding of the disease and what tools we had then compared to now. So maybe do you want to walk us through a little bit, kind of the history of treatment of alopecia?

Dr King: Yeah, I think it's really interesting to think about how quickly everything has changed. I feel like an interesting view of this is or are Jerry Shapiro's sort of every 8 or 10 year JAAD CME articles on alopecia areata. And in 2010, the JAAD CME described topical corticosteroids, intralesional triamcinolone, topical minoxidil, DPCP, SADBE, and then systemic corticosteroids, methotrexate, cyclosporine and counseling. All of these things were described. All of each of these things got a paragraph in the article about treatment of disease. And then 2018, his CME described JAK inhibitors and of course off label, but it was so clear in a short period of time that JAK inhibitors, oral JAK inhibitors had transformed or were transforming the treatment paradigm or the algorithm that all of a sudden the CME described JAK inhibitors and all of a sudden counseling was not there because I think it was apparent to those of us who were doing this a little bit more than everyone else, treatment had arrived. We were moving towards a new era and then holy cow, right, 2022, baricitinib is approved. 2023 ritlecitinib is approved, 2024 deuruxolitinib is approved. And you look at the treatment landscape or the investigational treatment landscape, clinical trials, holy cow, there are 6, 7, 8, 9, 10 clinical trials that have happened or are happening in this disease that truly, I think 12 years ago, pharma had not heard of alopecia areata, and now it's really an interesting disease to bring really interesting immunological, targeted immunological treatments to bear on to see if we can match oral JAK inhibitors or possibly do better than. So it's really exciting.

Dr Craiglow: Yeah, we've really come a long way in a short time. I think, alopecia areata, as long as someone hasn't been missing hair for many, many, many years, it really is largely a treatable disease. I think that as a community, I don't think that everybody's quite there yet with thinking that, but I think hopefully fast forward over the next five years that will sort of be the feeling, oh yeah, this is treatable. This is not something you have to live with forever. So Maryanne, tell us about JAK inhibitors a little bit and what you think about when you see a patient who is a good candidate and then maybe kind of talk us through. Well, let's start with that.

Dr Senna: Yeah. So first of all, I can't agree more with what Brett just said. I mean for all those different paragraphs up until 2018 that were written, the problem is even though you might've listed what 10 or 11 things, none of them worked right. Finally with JAK inhibitors, that one paragraph allowed us to now treat a whole population of patients with severe alopecia areata that we were never able to do much for before. And it was such an exciting time when we were doing these clinical trials and now to have these medications, FDA approved so that we can use them in patients and help patients get access to them has been so just absolutely transformative and our ability to give care. So when do I start thinking about giving a patient a JAK inhibitor? For me? I think if people have around 25, 30% scalp hair loss and they're not responding to other therapies, you see it's having an impact on their life and you just know that this is going to be a person who is just going to have, whether it's quickly or over a longer period of time, progression of their disease, that's when I start to say, the only thing that's really going to help this patient is to be on a JAK inhibitor. And of course you want to screen them to make sure that they don't have other really concerning comorbidities. Certainly someone with a history of a solid malignancy or a stroke or heart attack or something like that. You want to be careful about who you're, but by and large, this is a healthy patient population and nothing is going to work for patients in my opinion and experience like a JAK inhibitor is going to. So that's sort of when I start to think, and a lot of the data from the clinical trials have shown that getting treatment to patients earlier allows them to do better. So you don't want to wait until someone has near complete scalp hair loss or complete scalp hair loss or disease for 10 years that's more severe or moderate to severe because the likelihood of response, even to our best treatments, while they still can work, the percentages of people who tend to respond can go down. And so I feel like over time, I've been treating people a lot earlier and the outcomes have been great.

Dr Craiglow: Yeah, I mean there's sort of nothing like seeing that patient come back in, not only looking really different but feeling really different. It is very rewarding. I think that's something that maybe we don't talk about quite enough, but it is actually really fun to treat patients with JAK inhibitors and see them completely transform. And I think there is still some hesitation and lack of experience and all these things, but I think once you do it a couple of times you're like, oh, wow, I want to keep doing this.

Dr Senna: Short-term and long-term safety data too is very reassuring. We don't have 20 years of safety data yet with JAK inhibitors for AA, but the data that we do have with many of these medications, even in other indications shows them to be safe. And so I think with the efficacy we're seeing in AA, it only makes sense to get them to patients who need them.

Dr Craiglow: Yeah, I think a lot of people are curious about what that conversation should look like with a patient and how do you talk about the box warning and what do you say about risk? And so Brett, do you maybe want to walk us through what that might look like in your office to help people have an idea how to approach the conversation? I think if we don't do it a lot, it's a little overwhelming and I think the way in which we approach it can really influence a person's decision. And so I think knowing the data and knowing the data in our patients is really, really important.

Dr King: It really is. I think it's paramount that we have an understanding ourselves of the safety data because we are never going to be able to have this conversation in a meaningful way with the patient if we ourselves don't understand the data and have a certain level of comfort with it. But I think when we do, then we're really able to look at a patient, assess them properly and describe the warnings to them in a way that makes sense. Everybody, or very frequently I would say our patients come to us having read about these medicines. The alopecia areata community is unbelievably well-informed and connected online. And so they come often with questions about the warnings. They've read about them and they say, oh, but I read about them and I saw those warnings. And who in their right mind would say or sign up for a medicine if the discussion was, well, I can grow back your hair, but the medicines cause cancer, stroke, heart attack, blood clots, serious infections and death. And part of the problem with that description or that perception is that it's not true. I think of the clinical trial from which the warnings emerged that clinical trials of tofacitinib in older patients with cardiovascular disease who had rheumatoid arthritis. I really think of the data from that as a kind of a worst case scenario because just as both of you said, our patients are usually healthy. They're usually not 60 years of age, morbidly obese, also taking methotrexate, also taking prednisone, also with a history of premature coronary artery disease or hypertension or diabetes or the list goes on and on. Those are not our patients. And those were the patients in the tofacitinib RA study that gave us the boxed warnings. But let's just imagine that that was the risk. It says that if you monitor 3000 patients taking a JAK inhibitor for 5 years and you compare outcomes to 1500 people taking a TNF alpha inhibitor, again, and this is all in RA, that 4% of people taking the JAK inhibitor are going to have one of these events, cancer or a heart attack or stroke, and 3% roughly of patients taking the TNF alpha alpha inhibitor are going to have a malignancy or 3% of them are going to have a heart attack or stroke. That difference, that's a lot of patients to see that percentage of outcomes. And that's the worst case scenario. That, to me, says that these medicines don't even approach a place of unsafe. It simply says that a very simple set of questions about the patient sitting in front of us can really help us navigate the use of these medicines so that they are probably really safe. And so again, that's good for us to know, but I think it truly, you can describe everything that I just did in a minute and a half to a patient and 98% of them say, oh, that's really helpful. And most all of them will say, if you think that this is appropriate for me, I would like this medicine. And so it's just really important to understand the data and then to convey it and it can be conveyed quickly, efficiently, without diminishing any of the risk. I am always really clear to patients, I am not telling you that nothing bad is ever going to happen to somebody like you taking one of these medicines, but what I am saying is that it's going to happen so rarely that I am unlikely to ever take care of one of these patients, and I'm unlikely to know somebody who's going to take care of one of these patients to whom something bad happens. That's how often or how rarely one of these things will happen. And I really believe that is supported by the data.

Dr Senna: To your point, Brett, I think one of the better things that has come out from some of the data and what else is in the literature is when they show the incidence rates of these really scary side effects and they show that actually they fall right within the background rates of these things happening. In other words, in the AA population, the alopecia areata population, who's not on a JAK inhibitor, who's just walking around, almost like the general population, the likelihood of these things happening was the same as if you're not on a JAK inhibitor or approximates it. It's not like the risk jumps up tenfold or something like that based on the data that we have today. And I think that really helps people too. And just a plug too for the National Alopecia Areata Foundation, sometimes you'll occasionally get a patient who's more anxious or wants to do a deeper dive, clinics running late, you're trying to move things along. They have great videos on there that I send a lot of my patients to go and watch on safety and monitoring. I know you and Brit have done those. I have a few on there and I think I'll have patients watch those too. And those can be incredibly helpful because they kind of go through the data and go through the side effects in sort of a deeper way. So for anyone listening who might find that helpful too, I think that's helped some patients who might be a little bit more apprehensive, although I agree with you most once we have that short discussion and they understand, they feel much better about it.

Dr Craiglow: And I also think we all feel really comfortable with the safety, but even if the risk were higher, I think this is a population that is so interested in treatment that they are willing to accept a small amount of risk also, right? We are not gatekeepers. Our job is to give people information and then they make the decision that's right for them. And so again, I think as both of you have said, it's a lot about that patient in front of you, but you may have a patient who has some baseline risk factors and you may say to them, look, you already have a slightly increased risk of X, Y, or Z, and therefore your risk on this medicine might be more. I think there are plenty of patients who will say, I understand and I really want my life to feel back to normal, and so I'm willing to accept the risk. And then the other thing is some of these risk factors are modifiable. If somebody is overweight, they can try to work on their weight, get some exercise lipid control if they're not on a statin. There are some things actually, and this can be motivating for patients too. And so I think there usually can be a conversation around it, and I think it's not as intimidating as maybe it seems. And I think patients understand that that is uncertainty sometimes. But fortunately, we have all this data now to help guide these discussions. So let's just talk briefly maybe about a couple of either clinical scenarios or things that kind of come up with patients on JAK inhibitors, maybe those situations where it's maybe not so straightforward. I mean, we're lucky A lot of patients, they come in, they're missing hair, they start treatment three or four months later, they're growing hair, everything is great. But there are some patients who are slower to respond, who maybe respond in completely. And hair is really different from so many other diseases sort of the same. We can't apply the same rules to alopecia areata that we apply to atopic dermatitis or psoriasis, for example. So if we have a patient on a drug for atopic, a JAK inhibitor for atopic dermatitis, if in six or eight weeks they're really not much better, well, we can move on. And we see sometimes people with alopecia areata who they're not much better at six or eight weeks and somebody else has switched their medication already. But maybe Brett, you want to walk us through length of time to see a response and when you might think about switching and how this is different.

Dr King: So I think what's really great is that we now, because of the clinical trials, this is not sort of opinion, this is not sort of, well, best practice according to whoever the data from the baricitinib clinical trials, the data from the ritlecitinib clinical trials really very clearly shows that making a decision about treatment a failure before really, I don't think that you can do it with 100% confidence probably before month 12. You can do it with a lot of confidence at month 9. If you make a treatment decision at month 6, you're probably going to lose at least a third of potential responders who would have succeeded had you given them more time. But so sort of putting it all together, you never make a decision about failure before month 6, probably best month 9, just recognizing that it's really, we just all get it. It's really hard to tell somebody, oh no, keep going after month 9 for a 5% or possibly 10% chance of later success. Another thing actually that comes out of the baricitinib clinical trials is that restoration of eyebrows or eyelashes by month 9, even in somebody whose scalp is moving very slowly, scalp hair regrowth is moving very slowly. Eyebrows or eyelashes regrowth predicts in about a third of patients who've not achieved treatment success on their scalp. About a third of them if you keep going, will achieve treatment success on their scalp. And so it's sort of 6 to 9 months plus or minus. Looking for eyebrows or eyelashes regrowth, I think is really key to helping patients optimize their chances of success.

Dr Craiglow: And I think importantly, a switch would only be if a patient really truly isn't responding. We don't necessarily expect someone to have complete regrowth at this time, but if they're showing growth and they're continuing to make forward progress, then you're going to keep going. I think it becomes really tricky if you have a patient who has maybe 40, they started with absolutely no scalp hair and they regrow 40% and their eyebrows and eyelashes, but then they stall out, do you keep going? But the stakes are very high with hair. But I think in our clinics, we often do some things to try to optimize growth, whether it be adding oral minoxidil or intralesional. Marianne, do you want to tell us a little bit your sort of art of medicine with these patients? Because real life is not a clinical trial, right? We're lucky we can do do other things.

Dr Senna: Right. So yeah, I totally agree with what Brett said. I think we all agree on that, that you have to give people time, especially in severe cases. Sometimes, like Brett was saying, they'll regrow and they'll develop some patches for whatever reason, sometimes during their treatment or sometimes they'll regrow everything except for some areas of the scalp. And so depending on what that looks like, if it's a, well, first of all, I think all of us use oral minoxidil almost consistently with every patient. There's a real strong suggestion that using oral minoxidil in conjunction with JAK inhibitors can really help the hair I think come in a little bit quicker and a little bit better. And so that's the first thing that unless a patient really is struggling with multiple medications, that's something we're always recommending. And then filling in with intralesional steroids, sometimes if you want to give people a little push, you can even think about either using pulsed steroids or systemic steroids in addition to get them over a hump and eventually taper those off. That can work well. And using those things, like you said, can really help us achieve clinically meaningful regrowth in patients even to a greater extent than just the JAK inhibitors alone. I haven't had any success with topicals in this patient population. I get asked that a lot by other dermatologists or patients, and that is not something I reach for. But the other things that I mentioned are typical.

Dr Craiglow: Topical, especially topical JAK inhibitors, unfortunately have not really been shown to be effective in AA. Great. Yeah, I think it's an exciting time. We have options. And what's nice is also if you do have a patient that doesn't respond, there are other choices. And just because somebody doesn't grow hair on one JAK inhibitor doesn't mean they might not grow on a different one. Everybody's different. Everyone's physiology is different. The way they metabolize medications is different. And so it is completely reasonable and you should try a different drug. But importantly, you want to give it an appropriate length of time before you think about switching. And so I think we covered a lot about treatment. I don't know if either of you has any last pearls or thoughts before we move on.

Dr Senna: Just a quick minute on tapering. Patients sometimes want to taper and just the take home is there's not big safety data differences between lower dose, say baricitinib and 2 milligram and 4 milligram. If a patient's really compelled to want to do it for whatever reason, you just want to do it very slowly. You don't want to dose reduce them really quickly. You want to give them three months after any small change because we know it can take that long before you see what happens to their hair. So just an important take home message.

Dr Craiglow: Thank you for saying that. Really a really important point because I think a question that we almost always get asked is, well, what happens when you stop the medicine? Or patients will say, well, do you have to take it forever? And with most chronic diseases, if you want to have that disease treated, you have to continue therapy. And while there may be some patients who can ultimately discontinue treatment and maintain regrowth, the majority of patients require chronic therapy. And so we should, and again, because the stakes are high and because there's always a lag with hair, we don't want to ever just stop a patient. We don't even want to just cut the dose in half despite what the label for Baricitinib might say, right? In real life, a lot of patients are going to lose hair if you do that. And it's not going to be probably in the first several weeks, it's going to take some time, but once they start losing hair, it's kind of too late. You have to restart. And then you have to wait and think about how long it takes hair to grow. And if you have a patient, I mean, we have patients who it's two or three years before they stop wearing their wig even. And if that patient is somebody you just cut the dose in half or you say, oh, you've done great, we can stop. You could be putting them back in time three years. So any changes need to be done very thoughtfully and carefully, and ideally really not at all. But if you do think about a taper, it has to be sort of the slowest taper you've ever done with any medication. Okay, that was great. Thanks guys.