Journal of Clinical and Aesthetic Dermatology • Hot Topics in Alopecia November 2025 • EXPERT PERSPECTIVES

An interview with David Cotter, MD, PhD
Dr. Cotter is with Las Vegas Dermatology in Las Vegas, Nevada.

Dr. Cotter discusses deuruxolitinib, a recently approved JAK1/2 inhibitor for the treatment of patients with alopecia areata.

“Deuruxolitinib was originally approved in July 2024 based on two paired, randomized, double-blind, placebo-controlled trials, THRIVE-AA1 and THRIVE-AA2. In these studies, there were over 1,200 patients, all adults aged 18 to 65 years, with severe alopecia areata. The primary endpoint in the study was the proportion of patients that achieved a Severity of Alopecia Tool (SALT) score of 20, which is 80% scalp hair coverage at Week 24. On average, these patients had pretty severe AA, about 13% of their hair at baseline, so these were tough-to-treat cases.

If recognize the name deuruxolitinib, it’s because you’re familiar with ruxolitinib, which is a topical cream used to treat atopic dermatitis and vitiligo. Deuruxolitinib is a different molecule, in that instead of having hydrogen atoms, it has deuterium atoms, which are heavy hydrogen. Therefore, it has different pharmacogenetics and different pharmacokinetics, which is why it’s used differently. Thinking about the pharmacodynamics and pharmacokinetics of this drug, it’s different from some of our other Janus kinase (JAK) inhibitors we have currently available. The dose for deuruxolitinib for alopecia areata is 8mg by mouth twice daily (PO BID). It has a pretty quick half-life of about four hours, so within a day of missing a deuruxolitinib dose, nearly 90% or more is washed out of your system. With that fast “out,” we would also assume we’d have a fast “on,” and, in fact, this medication does.

One of the secondary endpoints in the THRIVE-AA1 and THRIVE-AA2 studies was looking at the proportion of patients that have that 80% regrowth of hair as early as Week 8, and that was a change in three percent of patients. While three percent may not sound like a lot, that’s an extremely quick endpoint for something like hair regrowth. When I think about where this drug may fill an unmet need for patients with alopecia areata, I think about fast onset of action. I think about it working extremely quickly and also having a pretty robust rate of regrowth at Week 24, with about 30% of the patients achieving SALT 20. When you look at network meta-analysis, which is the best that we have to do cross-trial comparisons, it looks like deuruxolitinib is going to be the most effective oral JAK inhibitor we have for alopecia areata at currently approved United States (US) Food and Drug Administration (FDA) doses. You can certainly dose other medicines higher, but with what we have that’s available in the US approved by the FDA at the current dosing, it looks like deuruxolitinib is going to be your best bet for your patients who want rapid and robust hair regrowth in the setting of alopecia areata.

Now, there’s a couple of things that make deuruxolitinib different, other than the BID dosing. This drug is metabolized by a special cytochrome P450 CYP2C9. What you need to know regarding that information for your patients is that we actually have to check the CYP2C9 genotype when we start the medication. If there are any dermatologists out there that remember prescribing azathioprine back in the day, we had to check a TPMT genotype, and based on the patient’s ability to metabolize azathioprine, we had to adjust the dose. With deuruxolitnib, it’s a little different. There’s no dose adjustment, but after you check the CYP2C9 genotype, if the patient is an extremely low metabolizer, that’d be someone that you should not put on deuruxolitinib.

The good news is Sun Pharma is paying for this genotype. It’s very simple to add on to your baseline labs, which you’re checking for JAK inhibitors anyway, so it shouldn’t delay the start of this medication. It’s just something to add on to your JAK start panel for your baseline blood work for your patients you’re considering for deuruxolitinib.

In addition, if someone is on a strong CYP2C9 inhibitor, then you might need to monitor them a little more closely, and maybe you wouldn’t use this medication. I run an interaction check if I’m going to start this medicine. To give you an example, while there aren’t too many medications we’re encountering in the dermatology world that are CYP2C9 inhibitors, one exception is fluconazole. There are other ones, like amiodarone, and I don’t have a lot of patients that are on amiodarone these days, particularly my patients with alopecia areata, but I’d encourage you to just run an interaction check to be extra safe before you write this medication.

In terms of safety, which is so important, especially with multiple different options to treat alopecia areata these days, this is a JAK inhibitor, so it comes with the normal boxed warnings and monitoring recommendations for JAK inhibitors; while those are the side effects that certainly we want to avoid at all costs for our patients, fortunately, they’re extremely rare, just like all other JAK inhibitors for alopecia areata. We just don’t see high rates of scary things like mortality, major adverse cardiac events (MACE), malignancy, thromboembolism, and even zoster in patients on deuruxolitnib occurs in less than 1% of patients. The event rate per 100 patient-years was less than two per 100 patient-years. Overall, deuruxolitinib is a very safe, clean JAK inhibitor, particularly in the alopecia areata population. The most common adverse events, the things that actually bother patients that you might encounter clinically, are things that we see in clinical trials—headaches in around 12%, acne in about 10%, nasopharyngitis in around 8%, and creatine phosphokinase (CPK) increases in about 5% of patients, but that’s not something we even monitor in our clinic. It’s outside of the JAK guidelines to even check for CPKs.

All in all, when I think about deuruxolitinib, I’m excited that we finally have it to treat our patients. It’s a fantastic new option for our patients who want robust and rapid regrowth of their hair. When you start it up, dose at 8mg PO BID. It has a fast “on” and fast “off” because it has a short half-life, which is probably why we see such rapid results in clinical trials. Make sure you check your CYP2C9 genotype, because if the patient is an extremely low metabolizer, as they would not be a candidate for deuruxolitnib.

Listen to the full audio of this exclusive JCAD interview with Dr. Cotter on our podcast page at jcadonline.com/jcad-podcast/

RESEARCH BITE—Evaluation of the efficacy and treatment-emergent adverse events of deuruxolitinib for moderate to severe alopecia areata: a dose-ranging meta-analysis of 1,372 randomized patients

This systematic review and meta-analysis assessed deuruxolitinib efficacy and safety for adults with moderate-to-severe alopecia areata across three randomized controlled trials (n=1372). At Week 24, deuruxolitinib significantly improved hair loss severity, with a Severity of Alopecia Tool (SALT) change from baseline mean difference [MD] of −47.26 (95% confidence interval: −53.47 to −41.05, p<0.00001), and markedly increased the proportions achieving SALT-75 (risk ratio [RR]: 93.66) and SALT-90 (RR: 65.26) versus placebo. Patient-reported hair satisfaction also improved (Hair Satisfaction Participants Reported Outcome [SPRO] MD = −1.52; ≥2-point improvement RR: 4.98). Both 8mg and 12mg twice daily were effective, with larger effects, but more side effects, generally observed at 12mg. By Week 28, treatment-emergent adverse events (TEAEs) included asymptomatic Grade 3–4 creatine phosphokinase elevations (RR: 2.79, p=0.0006), higher acne rates at 12mg (RR: 3.00, p=0.0005), and a modest increase in headache with 8mg (RR: 1.66, p=0.05), without increased upper respiratory infections or nasopharyngitis compared with placebo. The findings indicate that deuruxolitinib produces clinically meaningful hair regrowth and patient-reported benefits with manageable safety signals, warranting continued safety monitoring.

Source: Kalantan M, Bashrahil B, Aljuaid A, et al. Evaluation of the efficacy and treatment-emergent adverse events of deuruxolitinib for moderate to severe alopecia areata: a dose-ranging meta-analysis of 1,372 randomized patients. Front Med (Lausanne). 2025;12:1641245.