Justin M. Ko, MD, MBA

Credit: med.stanford.edu

Individuals with severe alopecia areata who have not achieved successful scalp hair regrowth on oral selective Janus kinase 1/2 inhibitor known as baricitinib, 2 mg, may benefit from raising the dosage to 4 mg, according to recent findings.¹

In the prior phase 3 BRAVE-AA1 and BRAVE-AA2 trials on adults with Severity of Alopecia Tool (SALT) scores of 50 or higher at baseline, baricitinib 2 mg and 4 mg were shown to be more effective than placebo in achieving scalp hair regrowth after 36 weeks.²

In these previous studies, at both 36 and 52 weeks, responses were reported with a higher response rate for baricitinib, 4 mg, versus a dose of 2 mg. Higher rates of response had also been seen in those with ‘severe’ SALT scores of 50 - 94 versus those with ‘very severe’ SALT scores of 95 - 100 at baseline.³

The latest research on this patient group was authored by Justin M. Ko, MD, MBA, from the Department of Dermatology at Stanford University’s School of Medicine.

Ko and colleagues “studied whether patients initially randomized to baricitinib, 2 mg, and who did not reach a SALT score of 20 or lower after 52 weeks of treatment would benefit from an uptitration to baricitinib, 4 mg, and additionally examined if factors such as baseline disease severity and duration of current AA episode were associated with the response to uptitration.”

Background and Findings

The investigators originally conducted the multicenter, phase 3 randomized clinical trials, known as BRAVE-AA1 and BRAVE-AA2, in September of 2018, and July of 2019, respectively, adding their follow-up with patients up to 200 weeks after. Data cutoffs were on November 11, 2021, and on November 5, 2021, respectively.

The team’s analysis assessed the long-term extension data up to 76 weeks, with baseline including 1200 adults with diagnoses of severe alopecia (SALT score ≥50), who were also randomly assigned in a 3:2:2 ratio to be given either baricitinib at 4 mg, baricitinib at 2 mg, or a placebo.

Participants on baricitinib kept up with the same dose until the 52 week mark, and participants with a reported SALT score of greater than 20 following 52 weeks on the treatment at 2 mg were labeled by the research team as nonresponders.

The primary outcomes decided upon by the investigators included the evaluation of the proportions of participants managing to achieve a SALT score of 20 or lower, in addition to assessing clinician-reported eyebrow and eyelash hair loss outcomes.

Specifically, the investigators analyzed scores of 0 or 1, which indicated full coverage or minimal gaps, and improvements of 2 points or higher from the point of baseline for participants with baseline scores of ≥2, indicating substantial gaps to no notable hair. They examined such measures throughout the study period which lasted up to week 76.

Following 52 weeks of treatment, the investigators reported that among the 340 participants—with a mean age of 38.4 years and 62.4% being female—who took baricitinib, 2 mg, they found that 62.4% showed SALT scores which exceeded 20 and were then escalated to the 4 mg dose.

Of this particular group, the research team noted that 67.0% initially presented with very severe baseline SALT scores of 95 - 100. By the point of week 76, the team indicated that 25.9% of these participants were shown to have achieved SALT scores of 20 or lower.

Simultaneously, the investigators found that response rates for clinician-reported outcome scores of either 0 or 1 showed some improvements, with the team noting that the amount rose from 19.3% of participants to 37.9% for eyebrows and from 24.1% to 40.9% for eyelashes.

Overall, the investigators suggested that a substantial proportion of these patients initially faced very severe cases of alopecia areata, yet a quarter of them were shown to have achieved notable improvement in their SALT scores by the 76 week mark.

“These data are important for health care professionals to consider when counseling patients on treatment expectations and the potential benefits of dose escalation,” they wrote. “Ultimately, some patients require a baricitinib, 4 mg, dose for optimal response to treatment, and these data help inform decisions around the use of uptitration in the context of nonresponse to baricitinib, 2 mg.”

References

1. ^{Ko JM, Mayo TT, Bergfeld WF, et al. Clinical Outcomes for Uptitration of Baricitinib Therapy in Patients With Severe Alopecia Areata: A Pooled Analysis of the BRAVE-AA1 and BRAVE-AA2 Trials. JAMA Dermatol. Published online August 09, 2023. doi:10.1001/jamadermatol.2023.2581.}
2. ^{Taylor SC, Korman NJ, Tsai TF. 33766 Efficacy of baricitinib in patients with various degrees of alopecia areata severity: results from BRAVE-AA1 and BRAVE-AA2. J Am Acad Dermatol. 2022;87(3)(suppl):AB52. doi:10.1016/j.jaad.2022.06.243.}
3. ^{Mayo T, Taylor S, Ito T, et al. Efficacy in subgroups related to disease characteristics in patients with alopecia areata from BRAVE-AA1 and BRAVE-AA2. Abstract presented at: 2023 American Academy of Dermatology Annual Meeting; March 17, 2023; New Orleans, LA.}