Utilizing CYP2C9 Testing and JAK Inhibitors for Alopecia Areata

In Irvine, California, Natasha A. Mesinkovska, MD, associate professor and vice chair for clinical research in the Department of Dermatology at the University of California, Irvine, led a Dermatology Times Case-Based Roundtable event focused on real-world use of Janus kinase (JAK) inhibitors and adjunctive therapies for alopecia areata (AA). Through 3 clinical cases, Mesinkovska and the attendees emphasized patient selection, psychosocial impact, safety, and lab monitoring.

Case 1: A 30-Year-Old Man With Scalp and Facial Involvement (SALT >40)

In the first case, a 30-year-old man presented with patchy scalp AA (Severity of ALopecia Tool [SALT] score of > 40 but < 50) with eyebrow and beard involvement. He had no comorbidities, but there was a family history of psoriasis. Several clinicians emphasized that depression and anxiety were the most common comorbidities they see, particularly in this age category. The attendees also noted that they mostly see younger adults (20s-30s) and teens in their own practices. A minority report substantial numbers in their 50s to 60s, raising the question of older patients simply accepting hair loss or not presenting for care.

Patients were commonly described as introverted and withdrawn, with frequent emotional distress and subtle functional impacts like school avoidance, job changes, and social withdrawal. Standard quality-of-life measures often fail to capture this in patients with “hardened” long-standing AA who deny impairment at baseline.

"I have tissues everywhere, because some of these [women]—more than men, maybe—come in, and they're very distraught. Just seeing clumps of hair fall out is very, very traumatizing,” one attendee said.

The clinicians agreed that facial involvement—particularly brows and beard—meaningfully “upgrades” perceived severity, even when scalp SALT is below the traditional threshold of greater than or equal to 50. Many favored early systemic treatment (including JAK inhibitors) in significantly affected patients, often with oral minoxidil as an adjunct. There was consensus that facial hair involvement justifies escalation, even when scalp SALT alone would be classified as “moderate.”

"Eyebrows, eyelashes, facial hair…I never knew how much it mattered to people. Apparently, it matters a lot,” Mesinkovska said. “In the trials, we actually had people [who] would stay on these medications for years, just for eyebrows and eyelashes.”

This patient underwent CYP2C9 genotype testing and then began a course of deuruxolitinib 8 mg twice daily. After 6 months, the patient’s scalp loss decreased to a SALT score of 10, with notable improvements in his beard and eyebrows and an increase in self-confidence.

Case 2: A 26-Year-Old Woman With Rapidly Progressive Disease

In the next case, a 26-year-old woman experienced rapid progression from SALT 10 to 70 over 3 months, seeking rapid regrowth as her wedding gets closer. Here, Mesinkovska and the attendees stressed clear expectation-setting with patients. Reliable cosmetic regrowth by a fixed date cannot be guaranteed, even with therapies like deuruxolitinib, which show relatively faster SALT responses. Parallel planning through wigs, extensions, and styling strategies is essential.

Preconception counseling is also mandatory; all agreed that JAK inhibitors should be discontinued during pregnancy. Short- to medium-term use (to achieve regrowth prepregnancy) was considered reasonable if risks are discussed and follow-up is reliable.

Many favored agents with the most extensive safety data in other indications (eg, baricitinib), especially in younger patients with future pregnancy plans. However, deuruxolitinib’s need for CYP2C9 testing was framed positively as “personalized medicine,” and it was chosen for this patient. After 6 months, she had a SALT score of 10.

Regarding treatment duration, most of the clinicians expect to see some signal by 6 months, but may not declare failure until approximately 9 to 12 months. They would consider switching JAK inhibitors after plateau or secondary loss of response, while warning patients that approximately one-third may worsen during transitions.

Case 3: A 48-Year-Old Woman With Sudden, Active, Patchy AA and Positive Hair Pull

The final case involved a woman with acute-onset, patchy AA with active shedding and a strongly positive hair-pull test. She had previously used topical minoxidil for a short period but discontinued due to irritation.

Even experienced clinicians across the country acknowledge a lingering emotional reluctance to start a JAK inhibitor at the very first episode of AA, despite robust efficacy and long-term experience from trials and other indications. However, many event attendees stated that they try to put patients on systemics as soon as possible.

"You are the leaders, the select, the nonfearful people…. Across the country, that’s not [the case],” Mesinkovska said.

For rapidly progressive disease, many favored a “kitchen sink” acute strategy, combining intralesional triamcinolone, oral minoxidil, and early introduction of a JAK inhibitor. CYP2C9 testing revealed that this patient was not a candidate for deuruxolitinib, so she was given oral ritlecitinib (50 mg once daily) and saw positive results.

Major risks such as major adverse cardiovascular events, venous thromboembolism (VTE), malignancy, and serious infections were contextualized: The highest signal arose in older, comorbid rheumatologic populations on higher doses. For patients with AA, especially younger ones in relatively good health, the group generally viewed absolute risks as low but nontrivial.

The most frequent adverse events were upper respiratory infections, headache, and folliculitis. Herpes zoster and VTE were rare in AA clinical trial programs. Acne was seen more in younger patients, often with a preexisting history. Overall, the dermatologists emphasized framing adverse effects realistically, providing comprehensive counseling on risks and realistic timelines for patients, especially when compared with what is printed on the box.

Conclusion

Across all 3 cases, Mesinkovska and the group converged on several themes: treat AA as a serious, high-burden disease; escalate earlier in appropriately selected patients; leverage JAK inhibitors with structured lab monitoring; and individualize choices based on age, comorbidities, reproductive plans, and patient priorities for speed vs safety. Personalized tools such as CYP2C9 testing for deuruxolitinib were viewed as the next step toward safer, more precise AA care.

“Biologics used to be considered scary at one point.... I think, in the future, all of these medications will be accepted as just something we’re familiar with,” one attendee concluded.