JAK Inhibitor Hesitancy and Step Therapy in Pediatric Alopecia Areata: A Q&A With Brittany Craiglow, MD

Despite growing use of Janus kinase (JAK) inhibitors in pediatric alopecia areata (AA), some dermatologists remain hesitant to prescribe them to younger patients, largely because of the class's FDA boxed warning. That warning was based on a 2022 trial of tofacitinib in patients with rheumatoid arthritis who were 50 years or older with at least 1 cardiovascular risk factor,¹ a population that looks little like the otherwise healthy children and adolescents dermatologists are treating for hair loss.

In the second installment of a 3-part interview with The American Journal of Managed Care^® (AJMC^®), Brittany G. Craiglow, MD, FAAD, a board-certified, fellowship-trained pediatric dermatologist and associate professor adjunct of dermatology at Yale School of Medicine who also practices at Middlebury Dermatology in Connecticut, explained where physician hesitancy toward JAK inhibitors comes from, how she discusses the boxed warning with families, and why she views step therapy policies that require patients to fail older treatments first as poorly suited to pediatric AA. Read part 1 here.

This transcript has been lightly edited for clarity.

AJMC: There's still hesitancy among some dermatologists about prescribing JAK inhibitors to younger patients. Where do you think that hesitancy comes from, and what does the evidence actually say?

Craiglow: I think the hesitancy probably first and foremost stems from the box warning that we have with JAK inhibitors. If you take it at face value, it's a lot, and it's something we have to talk to patients and families about. Especially if these medicines aren't something you're prescribing regularly, how to approach that conversation can be tricky, and having data to support the use of these drugs in our patients is really important. The box warning comes from a JAK inhibitor trial in patients with rheumatoid arthritis who were [50] years of age or older, on other immunomodulatory medicines, and who had at least 1 cardiovascular risk factor, those patients are often really different from the patients we're treating.

So it's important to give context, and talk about the data we see in patients with inflammatory skin disease, and that's a conversation that takes time. Another barrier is that many dermatologists don't have a ton of time in the visit with patients, so it can be tricky to get through all of that. What's really reassuring is that these medicines have been out for quite a long time now. In kids especially, we have data from other JAK inhibitors, in other disease states, or sometimes the same ones we use in alopecia areata, in kids as young as age 2 [years].

Several JAK inhibitors are actually approved down to age 2 for [juvenile idiopathic] arthritis. One, baricitinib, is approved also down to 2 for atopic dermatitis, not in the US, but in more than 40 countries worldwide. I often find myself saying, if this were arthritis, we would definitely be treating it; we wouldn't have some big, long conversation about this. I mean, we would have a conversation, but this sort of wishy-washy, "Oh, I don't know," and the hesitancy would look really different. But I think for most kids, alopecia areata can be as debilitating, albeit in a different way, as juvenile idiopathic arthritis.

So having context is really important, using the medicine so you gain a comfort level with it, but we do have this pretty big legacy of data now, in lots of diseases, including kids as young as 2, that really supports the safety of these medicines in pediatric patients.

AJMC: The JAK inhibitor class carries an FDA boxed warning. How do you discuss that with families, and how does the real-world safety profile in pediatric dermatology patients compare with the warning's framing?

Craiglow: It's really important to talk about the box warning, it's not something we should gloss over. It's part of the conversation, and I make sure I use all the words: it carries a label that says it's been associated with increased risk for blood clots, infection, major cardiovascular events, and cancer. I let that land, and oftentimes I say, "Yeah, I know it sounds like a lot. Let's talk about where that came from." Then I'll talk a little about the ORAL Surveillance study,¹ and then move to the data in patients with inflammatory skin disease. When we look across the board with JAK inhibitors, rates of the scary things in the box warning are very low, and they're exceedingly low in young patients. I tell people, I'm not saying the risk is zero, because there is some risk, but it's very low. In general, when you look at the rates of major adverse events among patients treated with JAK inhibitors for inflammatory skin disease, they tend to fall within the background rate, which suggests that we're probably not actually increasing risk by much, if at all, in our patients.

That said, some people have these things happen to them, if you're a patient taking one of these medicines and this happens, you're always going to think it was the medicine. So we have to feel comfortable with that. But I think most people are really reassured by the data.

And again, thinking about the risk of not treating, what does that mean? In many cases, it means literally forgoing your chance at ever having hair. We see kids come in who've had no hair for 4, 5, 6-plus years. That clock is ticking for that patient. If we don't treat now, they may actually never regrow hair. So I think that risk tends to be much higher than the risk of the drug. And of course, we have to ask about family history of clotting, and we need to know the patient's own medical history, and we do it in the safest way possible. But I think most people are willing to accept a small level of risk for a real chance at a normal life for their child.

AJMC: Step therapy policies often require patients to fail older, less effective treatments first. What's your clinical view of applying that logic to pediatric patients with AA?

Craiglow: In moderate to severe alopecia areata, there aren't many things that work. What's tricky with alopecia areata is that the timeline is really different from, say, treating a patient with psoriasis or atopic dermatitis, where you start a therapy and have an idea within about 8 to 12 weeks whether the patient's going to respond. With alopecia areata, the timeline is totally different, we look at primary endpoints in clinical trials that are either at 24 or 36 weeks, because hair takes a very long time to grow.

So if a payer tells me a patient has to fail a traditional immunomodulatory drug before a JAK inhibitor: number 1, those medicines haven't shown to be very effective in alopecia areata; number 2, I'd argue they carry more risk; and number 3, you're adding 6-plus months to the patient's journey. And just because hair is growing doesn't mean the patient feels normal, it often comes back patchy initially. In females, where it's more socially normal to have longer hair, it sometimes takes our patients 2 or 3 years to even remove their wig. So the timeline is very long, and making a patient step through something with a very low chance of working is really unfair to them. You're prolonging their suffering on a journey that's already really difficult.

References

1. Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. N Engl J Med. 2022;386(4):316-326. doi:10.1056/NEJMoa2109927