The selective JAK1 and JAK2 inhibitor baricitinib is effective in severe alopecia areata, according to two phase 3 trials.

The results from the randomised controlled trials, published in the NEJM and presented at the American Academy of Dermatology (AAD) 2022 Annual Meeting, involved 1,200 patients in total from 10 countries including Australia.

The patients had alopecia for at least six months and a baseline Severity of Alopecia Tool (SALT) score of ≥50 (0 = no scalp hair loss; 100 = complete scalp hair loss).

In both the BRAVE-AA1 and  BRAVE-AA2 studies, oral baricitinib at 4 mg and 2 mg doses was more effective than placebo in achieving the primary outcome of a SALT score of ≤20 at week 36.

In BRAVE-AA1, 38.8% of patients receiving 4 mg  baricitinib and 22.8% receiving 2 mg  baricitinib achieved the primary outcome compared to 6.2%  with  placebo.

The SALT score difference between 4-mg baricitinib and placebo was 32.6 percentage points (p<0.001), and between 2-mg baricitinib and placebo was 16.6 percentage points (p <0.001).

Alopecia areata is a distressing disorder of hair loss that is mediated partly by cytokines dependent on Janus kinases. The JAK1 and JAK2 inhibitor baricitinib reduced the extent of hair loss in two randomized trials over a period of 36 weeks. #AAD2022 https://t.co/oKKzGF7Q5S pic.twitter.com/gsgWJ1asZN

— NEJM (@NEJM) March 26, 2022

In BRAVE-AA2, the rates of achieving the primary outcome were 35.9% with 4mg baricitinib, 19.4% with 2 mg baricitinib, and 3.3% with placebo.

The SALT score differences between 4mg baricitinib and placebo were 32.6 percentage points (P<0.001) and 16.1 percentage points (P<0.001) between 2mg of the JAK inhibitor and placebo.

“Most patients in whom the primary outcome was met had SALT scores of 10 or less at week 36,” the study authors said.

Secondary outcomes such as the Clinician-Reported Outcome (ClinRO) measures for eyelash or eyebrow hair loss generally favoured baricitinib over placebo at the 4 mg dose but not at 2 mg.

The study reported adverse events such as acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo.

Serious infections included one case of COVID-19 pneumonia and two cases of pyelonephritis with baracitinib treatment. In BRAVE-AA1, a myocardial infarction occurred in a patient who received 2-mg baricitinib and had cardiovascular risk factors.

The percentages of patients who discontinued the trial regimen because of adverse events were low and similar across the trial groups – 1.1-1.8% in BRAVE-AA1 and 2.6% in BRAVE-AA2.

The researchers, including Melbourne dermatologist Professor Rodney Sinclair, concluded that once-daily oral baricitinib was superior to placebo with respect to hair regrowth.

“Longer trials are necessary to determine the efficacy and safety of baricitinib for alopecia areata, and the current trials are ongoing and are planned to remain randomised and blinded for up to 200 weeks,” they said.

The BRAVE-AA1 and BRAVE-AA2 trials were funded by Eli Lilly.