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BOSTON -- An oral Janus kinase (JAK) inhibitor produced significant, durable hair growth, including scalp, eyebrows, and eyelashes in patients with severe alopecia areata, according to long-term data from two randomized trials.

Almost 40% of patients achieved a Severity of Alopecia Tool (SALT) score ≤20 (total percentage of hair loss) at 52 weeks with a higher dose of baricitinib (Olumiant), and almost 30% had a SALT score ≤10. The patients had a mean SALT score >80 at baseline. Almost half of the patients had met response criteria for eyebrow and eyelash regrowth, reported Brett King, MD, PhD, of Yale School of Medicine in New Haven, Connecticut.

Adverse events (AEs) that occurred more often with baricitinib than with placebo were acne, elevated creatinine kinase levels, and increased LDL and HDL cholesterol, King said in a presentation at the American Academy of Dermatology (AAD) meeting.

The 52-week results showed continued improvement as compared with results after 36 weeks of follow-up, which were reported simultaneously in the .

"Continued treatment with baricitinib after 36 weeks resulted in further increases in the proportion of patients who achieved scalp, eyebrow, and eyelash hair regrowth," said King. "The proportion of patients achieving a SALT score <20 and/or a SALT score <10 -- and that's kind of a high bar -- continued to increase. The proportion of patients achieving ClinRO [Clinician Reported Outcome] for eyebrow and eyelash hair loss ... also continued to increase, restoring to nearly normal or normal."

"This is truly transformational for patients," he added. "These patients start out looking nothing like themselves, and they finish study, at least when it works, looking like themselves again, restored to normal."

Limited Treatment Options

An autoimmune condition with no approved therapies, alopecia areata affects men and women alike and causes rapid hair loss in the scalp, eyebrows, and eyelashes. The pathogenesis of the condition involves genetic and immune factors. Cytokines implicated in alopecia areata depend on the JAK pathway for intracellular signaling, providing a rationale for evaluating the therapeutic potential of JAK inhibition.

King reported findings from 52 weeks of follow-up in the BRAVE-AA1 and BRAVE-AA2 randomized, placebo-controlled evaluations of baricitinib in adults with active alopecia areata associated with a SALT score ≥50 (at least 50% hair loss). Investigators at 169 centers in 10 countries randomized 1,200 patients 2:2:3 to placebo, baricitinib 2 mg, or baricitinib 4 mg.

The primary endpoint was the proportion of patients achieving a SALT score ≤20 at 36 weeks. Secondary endpoints included a SALT score ≤10 and a ClinRO of 0 or 1 (full eyebrow/eyelash coverage or minimal gaps) with at least a 2-point improvement from baseline. The 52-week assessment focused on the same three outcomes. Patients allocated to the JAK inhibitor remained in their assigned dose groups, and placebo-treated patients with SALT score >20 switched to baricitinib after 36 weeks.

The study population had a median age of about 37, and women accounted for about 60% of all patients. About two-thirds of the patients had an alopecia duration of <4 years, and >40% had alopecia universalis. Baseline SALT score averaged about 85 across the placebo and baricitinib groups.

Key Results

The 36-week results showed that 34% of patients in the baricitinib 4-mg arm had a SALT score ≤20, as compared with 19.7% of the 2-mg arm, and 4.1% of the placebo group. At 52 weeks, the proportion of patients with SALT score ≤20 had increased to 39% with the 4-mg baricitinib dose and 22.6% with the lower dose.

For the more stringent SALT score ≤10, response rates at 36 weeks were 24.9%, 11.8%, and 2.3%, respectively for baricitinib 4 mg, baricitinib 2 mg, and placebo. Rates increased to 28.9% and 15.3% for the baricitinib arms at 52 weeks.

Rates of ClinRO response for eyebrows increased from 33.0% at 36 weeks to 44.1% at 52 weeks with the higher dose of baricitinib and from 15.8% to 22.9% with the 2-mg dose. In the placebo group, 3.8% of patients met ClinRO response criteria at 36 weeks.

Changes in ClinRO response for eyelashes from 36 to 52 weeks were 33.6% to 45.3% with baricitinib 4 mg and from 12.0% to 25.5% with baricitinib 2 mg. The placebo group had a 4.3% ClinRO response at 36 weeks.

In response to a question from the audience, King said patients with longstanding alopecia areata are not good candidates for treatment with the JAK inhibitor. A patient with a 10-year history of the hair loss is unlikely to benefit, although outliers do exist.

Similar results emerged from a subgroup analysis of placebo-controlled study of a different JAK inhibitor. An analysis of 105 adolescents (mean age 15) included in the overall study population showed that the JAK3/TEC inhibitor ritlecitinib led to SALT score ≤20 responses in 17%-28% of patients treated for 24 weeks with one of five doses of the drug. Additionally, 17%-28% of patients met criteria for SALT ≤10 responses.

From 22%-61% of patients treated with ritlecitinib rated results as improved or much improved on Patient Global Impression of Change index. The best results occurred in patients randomized to a 200-mg loading dose of the drug followed by 50 or 30 mg daily, reported Maria Hordinsky, MD, of the University of Minnesota in Minneapolis, and colleagues, in an AAD poster presentation. The most common AEs (including the placebo group) were headache, nasopharyngitis, and upper respiratory infection.

Ritlecitinib earned an designation in September 2018 for alopecia areata, while baricitinib is currently FDA approved for the treatment of adults with moderate-to-severe active , and as a treatment for COVID-19 with remdesivir (Veklury), per a 2020 .