JAK Inhibitors for Alopecia Areata: Clinical Insights and Emerging Strategies

At the Fall Clinical 2025 session, “Answers to Hair Questions: Alopecia Areata and Beyond,” Natasha Atanaskova-Mesinkovska, MD, PhD, presented a candid and case-based review of current treatment strategies for alopecia areata (AA), emphasizing the growing role of Janus kinase (JAK) inhibitors across diverse hair loss disorders.

Dr Atanaskova-Mesinkovska noted the clinical practicality of JAK inhibitors, highlighting their short half-life as a safety advantage. “If something goes wrong, they have a very short half-life, about 6 hours or less,” she explained. Drawing on over a decade of experience from clinical trials across various inflammatory skin conditions, including AA and atopic dermatitis, she underscored their overall tolerability: “Doxycycliine gives more drama from day to day than a lot of these medications do.”

Currently, 3 JAK inhibitors are approved for AA, each with unique pharmacologic features:

• Baricitinib (2 mg and 4 mg): Described as the “first baby” in this class, baricitinib remains a commonly used agent, with 4 mg being the standard dose in most cases.
• Ritlecitinib (50 mg): A once-daily capsule with JAK3 and TEC inhibition. Its simplicity in dosing is a key benefit. Importantly, ritlecitinib requires CYP2C9 genotyping to screen for poor metabolizers, a rare phenotype most often seen in Caucasian patients.
• Deuruxolitinib: A JAK1/JAK2 inhibitor given twice daily. While twice-a-day dosing is often perceived as less convenient, she noted a possible efficacy benefit.

Across trials, a responder is defined as a patient achieving 80% or more hair regrowth. Yet, as Dr Atanaskova-Mesinkovska emphasized, visible cosmetic improvements may fall short of that threshold but still hold clinical meaning. “This patient did not reach that score,” she said, referencing clinical images, “but it’s still a big change.”

She discouraged early discontinuation or switching between agents too soon. “Don’t go from one to the next if they grow a little bit of hair… Give them a chance, at least 6 to 9 months. Talk to them. This is going to have to be a long-term therapy because if you stop it, the hair will fall off.”

Acknowledging the black box warnings, she clarified their origin in rheumatoid arthritis trials and stressed the relatively low incidence of adverse events in dermatologic patients. “The things that we see are few and far between in alopecia patients,” she said. “We see is acne. You can put people on isotretinoin or doxycycline.”

Regarding safety signals:

• Opportunistic infections and candidiasis were not commonly observed.
• Zoster reactivation remains a consideration, although she does not routinely vaccinate.

Patient selection is key. Dr Atanaskova-Mesinkovska avoids JAK inhibitors in patients with:

• Malignancy within the past 5 years
• Significant cardiovascular disease
• Smoking history (vaping is now complicating this approach).

While ritlecitinib is US Food and Drug Administration approved for patients as young as age 12 years, access for younger children remains challenging. Off-label use may be guided by European precedents, where approval extends to children ages 2 years and up.

Importantly, Dr Atanaskova-Mesinkovska advocated for a broader diagnostic view. “To treat alopecia areata is to treat atopic dermatitis,” she argued, citing clinical patterns of seasonal flares and elevated IgE. “Especially in young adults—the skin flares, the hair is coming.”

She frequently adds antihistamines for patients with atopic features: “Platelet-activating factor  in the morning, cetirizine in the evening or dupilumab. We need higher doses [of dupilumab] to make it more efficacious.”

Eyebrows hold significant psychological impact in patients with AA. One of her most compelling anecdotes involved a patient who failed to regrow brows despite scalp recovery on ritlecitinib. He later responded to intralesional triamcinolone. “He was right, I was wrong”—an experience soon to be published in the Journal of Drugs in Dermatology.

She also emphasized the importance of patch testing, especially in patients with frontal fibrosing alopecia (FFA) or central centrifugal cicatricial alopecia. “People are allergic, from hair dyes to shampoos to even topical minoxidil… FFA, the bane of all of our existence—about 80% in certain studies will show to be positive on patch testing.”

Dr Atanaskova-Mesinkovska closed with cautionary notes on emerging therapies, such as:

• Google Ventures-backed topical agents: Although popularized online, initial studies showed only 30% efficacy in men, with minimal to no benefit in women.
• Exosomes: She warned clinicians to ask for evidence: “All of them include microneedling, laser, or some sort of transdermal, which gets you in legal water. So be careful.”

In summarizing the treatment landscape, Dr Atanaskova-Mesinkovska emphasized personalized care, clinical vigilance, and long-term management. “Start early—there’s nothing to fail. Just use it,” she said of JAK inhibitors. “Give patients time and guide them through it. This is not a sprint.”

Reference
Atanaskova-Mesinkovska N. Answers to hair questions: alopecia areata and beyond. Presented at: 2025 Fall Clinical Dermatology Conference. October 23–26, 2025; Virtual.