Dramatic and long-lasting hair growth with oral JAK inhibitor

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

Nearly 40% of patients achieved a Severity of Alopecia Tool (SALT) score ≤ 20 (percent total hair loss) at 52 weeks with a higher dose of baricitinib (Olumiant), and nearly 30% had a score SALT ≤ 10. Patients had a mean SALT score > 80 at baseline. Nearly half of the patients 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 meeting. from the American Academy of Dermatology (AAD).

Results at 52 weeks showed continued improvement over results at 36 weeks of follow-up, which were reported concurrently in the New England Journal of Medicine.

“Continuation of baricitinib treatment after 36 weeks resulted in a further increase in the proportion of patients who achieved scalp, eyebrow and eyelash hair regrowth,” King said. “The proportion of patients achieving a SALT score

“It’s truly transformational for patients,” he added. “These patients start looking nothing like themselves, and they finish their studies, at least when it works, looking like themselves again, restored to normal.”

Limited treatment options

An autoimmune disease with no approved therapies, alopecia areata affects both men and women and causes rapid hair loss from the scalp, eyebrows and eyelashes. The pathogenesis of the disease involves genetic and immune factors. The cytokines involved in alopecia areata depend on the JAK pathway for intracellular signaling, which warrants evaluation of the therapeutic potential of JAK inhibition.

King reported the results of 52 weeks of follow-up in the randomized, placebo-controlled BRAVE-AA1 and BRAVE-AA2 evaluations of baricitinib in adults with active alopecia associated with a SALT score ≥ 50 (at least 50% loss of hair). Investigators at 169 centers in 10 countries randomized 1,200 patients 2:2:3 to receive 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 brow/lash coverage or minimal gaps) with at least a 2-point improvement from baseline. The 52-week evaluation focused on the same three outcomes. Patients assigned to the JAK inhibitor remained in their assigned dose groups, and placebo-treated patients with a SALT score >20 crossed over to baricitinib after 36 weeks.

The study population had a median age of approximately 37 years and women comprised approximately 60% of all patients. Approximately two-thirds of patients had alopecia duration 40% had universal alopecia. The baseline SALT score averaged approximately 85 in the placebo and baricitinib groups.

Principle results

Results at 36 weeks showed that 34% of patients in the baricitinib 4 mg arm had a SALT score ≤ 20, compared to 19.7% in the 2 mg arm and 4.1% in the placebo group. At 52 weeks, the proportion of patients with an SALT score ≤ 20 had increased to 39% with the 4 mg dose of baricitinib and 22.6% with the lowest dose.

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

ClinRO response rates for eyebrows increased from 33.0% at 36 weeks to 44.1% at 52 weeks with the highest dose of baricitinib and from 15.8% to 22.9% with the 2 mg. In the placebo group, 3.8% of patients met the 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 12.0% to 25.5% with baricitinib 2 mg. The placebo group had a ClinRO response of 4.3% at 36 weeks.

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

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

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

Ritlecitinib gained a FDA Breakthrough Therapy designation in September 2018 for alopecia areata, while baricitinib is currently FDA approved for the treatment of adults with moderate to severe active alopecia. rheumatoid arthritisand as a treatment for COVID-19 with remdesivir (Veklury), by a 2020 FDA Emergency Use Authorization.

Disclosures

BRAVE-AA1 and BRAVE-AA2 were supported by Eli Lilly.

King disclosed his relationships with AbbVie, AltruBio, Almirall, AnaptysBio, Arena Pharmaceuticals, Bioniz Therapeutics, Bristol Myers Squibb, Concert Pharmaceuticals, Horizon Therapeutics, Eli Lilly, Incyte, LEO Pharma, Otsuka/Visterra, Pfizer, Regeneron, Sanofi/Genzyme, TWi Biotechnology, and Viela Bio.

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