Oral JAK inhibitor makes headway in alopecia areata

Patients with severe alopecia areata (patchy baldness) had a dramatic hair regrowth, without serious adverse events, when treated with an investigational Janus kinase (JAK) inhibitor in the phase III THRIVE-AA2 study presented at AAD 2023.

At 6 months, nearly 40 percent of patients who received deuroxolitinib had at least 80 percent scalp coverage with the 12-mg dose. Thirty-five percent of patients had a 90 percent or greater scalp coverage. The rest of the patients had at least 80 percent coverage with the 8-mg dose).

At 3 months, there was significant hair regrowth noticeable in most patients. Significant improvement in eyelash and eyebrow status were also evident in those who had problems in these areas.

“JAK inhibitors are changing the treatment paradigm for alopecia areata,” commented Dr Brett King from Yale Medicine in New Haven, Connecticut, US at AAD 2023. “THRIVE-AA2 included adults with a SALT* score of 50–100 (also represents percent of scalp hair loss), and an episode of severe hair loss.”

Deuroxolitinib was well tolerated. Seven patients had treatment-emergent adverse events. One discontinued treatment due to lack of efficacy.

THRIVE-AA2 cohort

The trial evaluated deuruxolitinib 8 or 12 mg twice daily in patients with moderate-to-severe alopecia areata (SALT ≥50).

 Mean age of the patients was 39. Two -thirds were female. Baseline mean SALT score was 88. The majority of patients had complete or near-complete hair loss. Seventy-five percent and 69 percent had eyebrow and eyelash involvement, respectively.

 Patients (n=517) were randomly assigned to higher or lower doses of deuruxolitinib, or placebo. The primary endpoint was the percentage of patients who had a SALT score ≤20 at 6 months.

 Improved scalp coverage

At 6 months, 38 percent of patients in the deuruxolitinib 12 mg arm had a SALT score of ≤20 whereas 33 percent had it in the 8-mg arm. This compared with 1 percent response rate in placebo-treated patients (p<0.0001).

Patients on the higher and lower doses of deuruxolitinib had significant hair regrowth relative to those on placebo from 2 months onward. Most patients in the two deuruxolitinib arms achieved the secondary endpoint of a SALT score ≤10 at 6 months (35 percent and 21 percent, respectively, p<0.0001).

For patients with eyebrow involvement, the mean BETA score improved from 1.1 to 2.4 in the deuruxolitinib 12 mg arm and from 0.7 to 2.0 in the 8-mg arm. As for placebo, there was a decline in BETA score from 0.9 to 0.6.

Mean BELA score for lash involvement increased from 1.1 to 2.6 and 0.9 to 2.2 in the 12- and 8-mg deuruxolitinib arms but remained unchanged in the placebo arm.

Patient satisfaction (satisfied or very satisfied) also improved from 46.4 percent to 51.7 percent with deuruxolitinib and 1.7 percent with placebo (p<0.0001).

Life-changing for patients

King presented several before-and-after photos of alopecia areata during his talk. “The photos tell the whole story … this is why there is so much excitement about this drug.”

“Alopecia areata has devastating effects on patients’ quality of life,” he added. “With the emergence of effective treatment, we are literally transforming the lives of these patients.”