Brett King, MD

 We’re getting toward the end. Other disease states are being studied with JAK inhibitors. Talk about granuloma annulare, sarcoidosis, and lichen planus.

It feels like the sky is the limit. A 5-patient prospective open-label clinical trial using tofacitinib recently showed amazing results with severe granuloma annulare. With sarcoidosis, we can often evaporate skin disease and watch internal organ disease go away. With severe oral lichen planus, we can make it go away. There was a recent publication in 

—not a prospective clinical trial, but upadacitinib in a real-world setting of patients with hidradenitis suppurativa—in which patients who had not previously achieved success, were achieving success. I really believe that JAK inhibitors are going to continue to wow us and show us that there’s possibility where we thought that there was nothing for patients.

 As we embarked 20 years ago on biologic therapy in psoriasis, it was like we needed a cookbook because we didn’t know what to do. We’re learning along the way. I agree that we have to collaborate with other physicians to make some of these tougher decisions.

I want to thank you, Dr King, for coming here for this wonderful, insightful discussion. Thank you to our audience for watching this 

® discussion to be useful and informative. Thank you very much.

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Experts in dermatology review how JAK inhibitors will impact dermatology care across the board.

Use of JAK Inhibitors in Granuloma Annulare, Sarcoidosis, and Lichen Planus 

How do you monitor your oral JAK patients? What blood work do you do before? What’s your standard follow-up?

What gets in the way of uptake of these medicines is if we feel, “Every time I use this 1, I have to monitor a little differently. Every time I use that 1, I’m going to have to monitor a little differently.” Even abiding by the label or what the drug companies are telling us to do, we need to screen prior to starting therapy. We’re going to check for tuberculosis, hepatitis B, hepatitis C, and complete blood count with differential LFTs [liver function tests]. Personally, I think a complete metabolic panel—throw in a creatinine test—because some of these are going to be dosed a little differently if you have moderate renal impairment. What’s a little different is fasting lipids.

Exactly. We’re on the same page. You start it there. When do you check again?

This is where having more of a 1-size-fits-all approach as opposed to, “This label says to check lipids at 12 weeks, and this 1 says 4 weeks.” Four weeks in, check CBC [complete blood count], LFTs or CMP [comprehensive metabolic panel], and then at 12 weeks or longer check fasting lipids. This is important; checking the fasting lipids out at a later time point is important because with more than 1 of these medicines, it’s been shown that some people will have an early rise in lipids that will return to their baseline at week 12. We don’t want to be checking a lab value and then feel, “Now I need to worry about cholesterol.” If you had just waited another 8 weeks, you don’t.

This is the thing: if lipids are normal at 12 weeks or thereafter, we don’t have to check them again. JAK inhibitors are not going to be onerous. Indeed, the label for the ones that we have in dermatology—upadacitinib, abrocitinib, baricitinib—all say 

 That means CBC and LFTs as you wish. That’s a gift. That means every 6 months for me.

Likewise, we’re on the same page. That’s what I’m doing. I’ve learned a little about this from the rheumatology colleagues who have been using it for longer than we have. I feel pretty comfortable about that.

I’m going to throw out some concepts. Let’s say someone is going on a JAK inhibitor who had a malignancy 3 years ago—not a lymphoma, but something like breast cancer or prostate cancer.

I’m a huge believer in shared decision-making. I’m not the doctor who knows what’s best for you. I like telling you what I believe to be true and letting you decide. Does that mean that for a patient who has recovered from metastatic disease 3 years ago, I’m going to invite them to use an oral JAK inhibitor? No, but it’s nuanced. Some things you’ll be able to wrap your mind around, and some are going to be a hard stop. If we had enough time, we could draw 5 scenarios on a white board. Some of them are going to be hard stops, and some of them are not.

A lot of this is going to be how each of us feels. Over time, we’re going to feel differently. We’re going to use these medicines once or twice. What’s amazing about the class of medicines across all these indications—we don’t even need to specify the indication—is that they’re really effective. You’re not going to have to treat even 2 patients with atopic dermatitis to have a success story and be wowed with the potential. You’re not going to have to treat 2 or 3 patients with alopecia areata to realize how much fun it is to watch somebody grow hair. You’re not going to have to treat 2 or 3 or 4 patients with vitiligo to watch their face return to normal and be absolutely dazzled by the possibility.

Everybody needs to start somewhere. Patient by patient, we’ll get more comfortable. These are complicated questions. For the patient with a malignancy 3 years ago, at the start they’re going to be a hard no. But 3 years in we might have a different feeling.

Jerry Bagel, MD, MS, and Brett King, MD, PhD, consider how new advances in oral medication will impact physicians’ and patients’ decision-making when it comes to treatment of alopecia areata, vitiligo, and atopic dermatitis.

Patient Preference & Shared Decision Making in JAK Inhibitor Selection

Now we have a medication. Could you possibly explain what you think is the pathogenesis of vitiligo...and the role of the JAK inhibitor in that pathogenesis?

One of the fun things about JAK inhibitors in general is they have the potential to make clinically important immunology fun. None of us went into dermatology because we were immunologists, or necessarily interested in immunology, but nevertheless when we understand why we’re using a medicine in a disease, it’s certainly much more fun than if we’re just randomly writing prescriptions. In the case of vitiligo, we believe that interferon gamma or IL-15, we believe that these 2 important cytokines are driving that disease to happen. They’re part of what’s driving the interaction between T cells and keratinocytes that lead to T-cell destruction of melanocytes and eventually a white spot. Both interferon gamma and IL-15 signal throw the JAK stat pathway. JAK inhibitors were deliberately used in vitiligo based on the data that say that interferon gamma and IL-15 are important drivers of this disease. I gave a patient oral tofacitinib, going back 7 or 8 years now, because the science said that it might interrupt her disease, and it did. Then we…brought ruxolitinib cream to the disease, and here we are all these years later with a drug that works and it’s targeted therapy for this disease.

With the development of treatment for patients with vitiligo, there’s obviously now a pipeline, ritlecitinib; how does that differ? How does that work? What expectations do you consider?

What’s really exciting...is ritlecitinib is in phase 3 clinical trials for moderate to severe alopecia areata. It’s in earlier stage clinical trials for vitiligo. Ritlecitinib is an oral JAK inhibitor. It’s a quite selective JAK-3 inhibitor, so getting back to the earlier part of our discussion about selectivity, again to the extent that selectivity is real when somebody actually puts one of these medicines in their body; it is a JAK-3 inhibitor. The data in alopecia areata are really promising and in vitiligo the data that we’ve seen to date are provocative. Not at the level of ruxolitinib cream, but I believe very much that that was clinical trial design and not a failure of the drug. In vitiligo, we need systemic therapy. It’s absolutely true; vitiligo is not a disease that always targets a patch of skin for which a topical can be used effectively. Patients with vitiligo often come in with generalized disease. We can’t prescribe enough cream, and nor do patients want to put cream necessarily all over their body and so we need an oral. We need a systemic therapy for vitiligo and I’m very hopeful that the next stage of clinical trials for ritlecitinib will bear out that that is a drug with really promising efficacy so that we have a second tool in our toolbox for this disease.

Dermatology experts discuss clinical specifics of JAK [Janus kinase] inhibitors and their impact on the treatment of patients with vitiligo and alopecia areata.

The Role of JAK Inhibitors in Treatment of Vitiligo and Alopecia Areata

 The topical JAKs [Janus kinase Inhibitors], could you talk about the topical JAKs, what their indications are, where you might use them, and risks?

Right now, we have ruxolitinib 1.5% cream. Again, it’s first indication for mild to moderate atopic dermatitis, and then very recently, it was approved for vitiligo down to age 12, which is important. The data for ruxolitinib 1.5% cream in mild to moderate atopic dermatitis are outstanding; most of us who have used it feel like it’s changed the management of mild to moderate atopic dermatitis. I think it really stands alone as a topical with steroid-like efficacy without steroid-adverse events.

 It’s nice to be able to write 1 prescription for a patient’s total body and it’s nice for the patient not to get 3 co-pays for 3 different scripts. The question there is, can you use a topical JAK inhibitor with an oral JAK inhibitor?...

If we abide by the labels, the label for ruxolitinib 1.5% cream says not to be used in combination with anything. Truly it’s not that expensive, but it says not to be used in combination with biologics or other JAK inhibitors. That to me means that we can use it only by itself or for a patient on phototherapy. No, this isn’t how we practice medicine in dermatology. Patients very frequently need more than 1 thing. For example, I use ruxolitinib 1.5% cream in combination with dupilumab. Sometimes you really do want that particular drug because if they’re having say facial dermatitis, I’m not going to smear their face in clobetasol, and so it’s a perfect treatment.

 What I’ve done and I’m sure you’ve done this too: You want to get a patient on a systemic JAK or a biologic agent for their atopic dermatitis, but in the meantime, you give them a topical JAK inhibitor in the 2 to 3 weeks that it’s going to take you to see if you can get the medication approved. And then you get this figure, a 25% to 30% chance that they might be better just on the topical, then you don’t have to go to the systemic treatment. I like that approach and I agree with you, I think topical JAKs have changed really the treatment paradigm for patients with atopic dermatitis. How do you find the efficacy of the topical JAK for vitiligo?

Ruxolitinib 1.5% cream, is an enormous advancement. It’s the first FDA-approved treatment for repigmentation of vitiligo; this is a historic achievement. It is really important to communicate and for all of us to understand. The great data for ruxolitinib cream in vitiligo are for the face. If we don’t understand that and we extrapolate the data for efficacy from the face to the other body sites, we’re going to be disappointed, but again, the data say that it works less well for body sites. It works very well for the face. One-third of patients using ruxolitinib 1.5% cream, twice a day for 24 weeks (1 time per day and the efficacy will significantly drop) will have a 75% improvement in their facial vitiligo. You take all the areas, shrink them by 75%. Now over a year, that becomes 50% of patients and over that same period of time, a year, one-third of patients will have a 90% improvement in their facial vitiligo. There’s a message here, similar to the message earlier for the management of alopecia areata. This disease takes time. Everybody who’s used ruxolitinib cream in atopic dermatitis find that patients will get relief of itch promptly and their dermatitis will improve within days. Vitiligo repigmenting skin is like regrowing a hair. It takes several weeks, so we have to be patient. This is not the sort of thing where you give a patient a prescription and say, come back in 4 months to see if you’re better. We need to give this time….

Do you happen to know the demographics, diversification, ethnicity in the patient populations they were dealing with?

Everybody was represented but there were not as many [individuals] of color as we would have hoped. It’s inescapable. When we think about vitiligo, we think about darkly pigmented patients. It happens to everybody. It is an equal opportunity disease. It affects all races, all ethnicities similarly, but we think about our patients with pigment in their skin first thing when we think about this disease. It’s unfortunate that more darkly pigmented patients were not better represented in these studies.

It’s FDA approved down to the age of 12?

Dermatologists have an important role. It’s tough to develop normally. It’s tough to go to school and learn and do the things that we’re charged with doing as children when we look really different from everybody else, when we’re missing hair, when we have white spots on our skin, when we are itchy. The approval of ruxolitinib cream down to age 12 is extremely important. By the way, this was something that I failed to point out earlier with upadacitinib’s approval for moderate to severe AD. It is also approved down to age 12. Age speaks a little bit to safety, doesn’t it?

When we have data in younger populations and we don’t see the adverse events that are keeping us up at night because of the boxed warning in those populations, I think that that tells us something about safety. For me it’s hugely important.

Jerry Bagel, MD, MS, and Brett King, MD, PhD, discuss the use of topical JAK inhibitors in alopecia areata, vitiligo, and atopic dermatitis.

Brett King, MD

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