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NEW ORLEANS -- Patients with severe alopecia areata had dramatic hair regrowth at 6 months with an investigational Janus kinase (JAK) inhibitor, according to a study reported here.

Almost 40% of patients had at least 80% scalp coverage with the higher of two doses of the JAK 1/2 inhibitor deuruxolitinib (CTP-543), including 35% who had 90% or greater scalp coverage. A third of patients had at least 80% coverage with the lower dose. Significant hair regrowth was evident by week 12 of the 24-week randomized trial. Significant improvement in eyelash and eyebrow status also occurred in the patients who had involvement of those areas.

The drug was well tolerated, as treatment-emergent adverse events occurred in seven of 387 patients treated with deuruxolitinib. Only one patient discontinued treatment because of lack of efficacy, said Brett A. King, MD, PhD, of Yale Medicine in New Haven, Connecticut, at the American Academy of Dermatology (AAD) annual meeting.

"JAK inhibitors are changing the treatment paradigm for alopecia areata," said King. "What we're reporting here are the results of a phase III clinical trial including adults patients with a SALT [Severity of Alopecia Tool] score of 50 to 100, that is 50-to-100 percent scalp hair loss, and a current episode of severe hair loss."

Additionally, long-term data from two randomized trials of the JAK inhibitor baricitinib (Olumiant) in alopecia areata showed durable effects, as 90% of patients who met response criteria at 52 weeks maintained the status at 104 weeks, reported Maryanne M. Senna, MD, of the Lahey Hospital and Medical Center in Burlington, Massachusetts.

Changing the Paradigm

King presented primary results from the phase III, randomized, placebo-controlled trial evaluating two doses of deuruxolitinib (8 or 12 mg BID) in patients with moderate-to-severe alopecia areata (SALT ≥50). The primary endpoint was the percentage of patients who had a SALT score ≤20 after 24 weeks.

The trial included 517 patients randomized 1:2:1 to placebo, 8 mg, or 12 mg of deuruxolitinib. The cohort had a mean age of 39, and women accounted for two-thirds of the total. The patients had a baseline mean SALT score of 88, or 88% scalp hair loss, and 61% of the patients had complete or near-complete hair loss (SALT ≥95). Three-fourths of the patients had eyebrow involvement, and 69% had eyelash involvement.

The primary analysis showed a 38% response rate (SALT ≤20) at 24 weeks with 12-mg deuruxolitinib and 33% with the 8-mg dose. That compared with 1% of the placebo-treated patients (P<0.0001). Both deuruxolitinib groups had significant hair regrowth versus placebo from week 8 onward (P<0.001, P<0.0001 at all time points). Most patients in the 12- and 8-mg groups achieved the secondary endpoint of a SALT score ≤10 at 24 weeks (35%, 21%, respectively, P<0.0001).

For patients with eyebrow involvement, the mean BETA score increased from 1.1 to 2.4 with deuruxolitinib 12 mg and from 0.7 to 2.0 with the 8-mg dose, as compared with a decline from 0.9 to 0.6 with placebo. 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 (P<0001 for eyebrows and eyelashes).

Patient satisfaction (satisfied or very satisfied) was 46.4% to 51.7% with deuruxolitinib and 1.7% with placebo (P<0.0001). The overall discontinuation rate was 9.5% and did not vary significantly among treatment groups.

Durable Results

As reported at the 2022 AAD meeting, baricitinib led to SALT ≤20 responses in 40% of patients with moderate/severe alopecia and SALT ≤10 in 30% after 52 weeks of follow-up in the phase III BRAVE-AA1 and BRAVE-AA2 trials (1,200 patients combined). Senna reported findings from continued follow-up to 104 weeks.

Patients who met response criteria at 52 weeks with baricitinib 2 or 4 mg QD continued treatment at the same dose. Investigators also evaluated the effect of continued treatment with 4 mg QD in patients who achieved partial response, defined as SALT >20 at 52 weeks but ≤20 at an earlier point in time. Partial responders also included patients with eyelash/eyebrow involvement who met response criteria (≥2) at some point before 52 weeks, but at 52 weeks.

The 104-week analysis consisted of 65 patients from the 2-mg group and 129 from the 4-mg group, as well as 110 partial responders. Alopecia areata duration averaged 11 to 12 years. Responding patients were more likely to have a current episode duration of <4 years (76-83%), whereas more patients with partial response (35%) had a current episode duration of ≥4 years, Senna noted.

Partial responders had more severe alopecia at baseline (SALT 93.4 vs 77-80), and three-fourths of the partial responders had SALT ≥95 versus about a third of responding patients, she added.

The primary analysis showed that 90.7% of patients in the 4-mg arm and 89.2% of patients in the 2-mg arm maintained responses between weeks 52 and 104. The proportion of patients who met response criteria for eyebrows and eyelashes continued to increase after 52 weeks in both baricitinib arms.

Analysis of the mixed responders showed that 39% met SALT response criteria at 104 weeks. Mixed responders maintained eyelash and eyebrow regrowth between weeks 52 and 104.

Patients expressed high levels of satisfaction with the treatment, and satisfaction rates could go even higher with inclusion of patients "sitting on the precipice" with SALT scores of 20 to 30, said Senna.

In his introductory remarks, King said alopecia areata has devastating effects on patients' quality of life and that with the emergence of effective treatment "we're literally transforming the lives of these patients, forever." AAD session moderator Andrew Blauvelt, MD, of Oregon Medical Research Center in Portland, referred to King's comments and expressed frustration with insurers' reluctance to pay for a "cosmetic" treatment.

King agreed but said insurers' attitudes have begun to change as recognition of transformative effects of JAK inhibitors on the condition has increased. Initially, he had to file multiple appeals on behalf of almost every patient prescribed a JAK inhibitor for alopecia areata. Recently, the number has dropped to about 30%, he said.

JAK inhibitors are not for the more common forms of hair loss, such as male androgenetic alopecia, which arises from a "totally different mechanism," said Paul Nghiem, MD, PhD, of the University of Washington in Seattle. Though clearly effective in alopecia areata, the long-term safety of JAK inhibitors remains unclear and will continue to be evaluated, he told 名媛直播. Hair loss returns when patients stop treatment, meaning that life-long therapy will probably be necessary to maintain hair regrowth.