Baricitinib may improve hair regrowth in alopecia areata

A once-daily dose of oral baricitinib may encourage hair regrowth in patients with severe alopecia areata, according to results of the phase III BRAVE-AA studies presented at AAD 2022.

Participants in the multinational, double-blind BRAVE-AA1 and BRAVE-AA2 trials were adults (n=654 and 546, respectively; age 18–60 years [male] or 18–70 years [female]) with severe alopecia areata and a SALT* score of ≥50. They were randomized 3:2:2 to receive baricitinib 4 mg, baricitinib 2 mg, or placebo QD for 36 weeks. Use of other treatments for alopecia areata was prohibited during the study.

The current episode of alopecia areata had lasted a mean 3.6 and 4.3 years in the BRAVE-AA1 and BRAVE-AA2 participants, respectively. Fifty-three percent of patients had very severe alopecia areata (SALT score 95–100) and 90.6 percent had received ≥1 prior treatment for the disease.

At week 36, 38.8, 22.8, and 6.2 percent of patients in BRAVE-AA1 treated with baricitinib 4mg, 2 mg, and placebo, respectively, achieved a SALT score ≤20. The respective percentages in BRAVE-AA2 were 35.9, 19.4, and 3.3 percent. [AAD 2022, session S026; N Engl J Med 2022;doi:10.1056/NEJMoa2110343]

There was a 32.6 percentage point difference between baricitinib 4 mg and placebo and a 16.6 percentage point difference between baricitinib 2 mg and placebo in BRAVE-AA1 (p<0.001 for each baricitinib dose vs placebo). In BRAVE-AA2, there was a 32.6 percentage point difference between baricitinib 4 mg and placebo and a 16.1 percentage point difference between baricitinib 2 mg and placebo (p<0.001 for each baricitinib dose vs placebo).

New or worsening adverse events (AEs) were reported in 59.6, 50.8, and 51.3 percent of baricitinib 4 mg, 2 mg, and placebo recipients, respectively, in BRAVE-AA1, and 66.1, 68.4, and 63.0 percent, respectively, in BRAVE-AA2. Serious AEs were reported in 2.1, 2.2, and 1.6 percent, respectively, in BRAVE-AA1, and 3.4, 2.6, and 1.9 percent, respectively, in BRAVE-AA2.

AEs that were more common with baricitinib than placebo were acne (BRAVE-AA1: 5.7, 5.5, and 0.5 percent with baricitinib 4 mg, 2 mg, and placebo recipients, respectively; BRAVE-AA2: 4.7, 5.8, and 1.9 percent, respectively) and in BRAVE-AA2, urinary tract infections (4.7, 7.7, and 1.3 percent, respectively). Infections were reported in 31.4, 25.1, and 28.0 percent of baricitinib 4 mg, 2 mg, and placebo recipients, respectively, in BRAVE-AA1, and 29.6, 37.4, and 29.2 percent, respectively, in BRAVE-AA2. Herpes zoster infection rate was low (BRAVE-AA1: n=2, 1, and 1, respectively; BRAVE-AA2: n=3, 3, and 1, respectively), localized, and not disseminated.

There was one case each of COVID-19 pneumonia, pyelonephritis, and myocardial infarction in baricitinib 2 mg recipients, one case each of pyelonephritis and B-cell lymphoma in baricitinib 4 mg recipients, and one case of prostate cancer in a placebo recipient. There were no incidents of venous thromboembolism, opportunistic infections, or gastrointestinal perforations.

Among baricitinib recipients, LDL-cholesterol elevations occurred in about 25 percent and HDL-cholesterol elevations in about 40 percent. More baricitinib 4 mg than placebo recipients experienced elevated creatine kinase levels (BRAVE-AA1: 5.7, 1.6, and 1.6 percent in baricitinib 4 mg, 2 mg, and placebo recipients, respectively; BRAVE-AA2: 3.0, 0, and 1.3 percent, respectively).

“In the current trials involving adults with severe alopecia areata, baricitinib was superior to placebo with respect to hair regrowth at 36 weeks,” said the authors. “Most patients in whom the primary outcome was met had SALT scores of ≤10 at week 36.”

“The results for most key secondary outcomes with 4 mg baricitinib [but not 2 mg baricitinib] supported the results for the primary outcome,” they added.

The authors noted that the trials are ongoing to assess long-term safety of baricitinib in this patient population.