Ongoing treatment required in severe patchy hair loss

For patients with severe alopecia areata who achieved meaningful hair regrowth with 1-year course of baricitinib, subsequent discontinuation appears to reverse treatment gains, highlighting the need for ongoing therapy.

In the randomized withdrawal substudy of the phase III BRAVE-AA1 trial, between 10 percent and 11 percent of patients experienced treatment benefit loss (defined as >20-point worsening in SALT* score) within 8 weeks of switching to placebo from baricitinib (2 or 4 mg), with the numbers increasing over time. [JAMA Dermatol 2024;doi:10.1001/jamadermatol.2024.2734]

A >20-point worsening in SALT score had occurred in at least half of the patients by 24 weeks after baricitinib withdrawal (60 percent in the 4-mg cohort and 50 percent in the 2-mg cohort) and in 80 percent (in both dose cohorts) by week 152.

In contrast, only 7 percent of those who remained taking their initial dose of baricitinib had experienced a >20-point worsening in SALT score by week 152.

The loss of treatment benefit observed here was consistent with reports in the literature of relapses with withdrawal of other systemic therapies in alopecia areata, according to the investigators. [Dermatol Ther (Heidelb) 2023;13:2951-2991]

Meanwhile, retreatment with the initial dose of baricitinib resulted in hair regrowth, although with varying trajectories, they added. Retreatment was initiated upon worsening of greater than 20 points in absolute SALT score.

During the retreatment period, 87.5 percent of patients who were retreated with 4-mg baricitinib and 63 percent of those who were retreated with the 2-mg dose recaptured response of a SALT score of 20 or less.

“As illustrated by individual patient trajectories, not only is the time to disease recurrence variable, but also the rate and extent of hair loss (once it begins) varies considerably across patients, with some losing most hair during a short period,” the investigators noted.

“At the point of observation in this article, not all patients had recaptured efficacy, although recapture rates increased progressively over time. Similarly, in a trial of ritlecitinib, not all patients who underwent treatment withdrawal recaptured response,” they added. [J Am Acad Dermatol 2022;87:390-39]

In clinical practice, if treatment discontinuation is considered, retreatment at the earliest sign of shedding must be done to stabilize the disease and recapture response, according to the investigators. Early shedding may be identified by positive findings on a hair pull test, although this approach has not been validated for this purpose or for disease monitoring during JAK inhibitor treatment withdrawal.

Referencing data from BRAVE-AA clinical trials, the investigators stated that interruptions of treatment should be limited to 4 weeks or fewer. However, some patients in the trials, albeit in rare cases, were able to maintain hair growth even after stopping treatment for 2 years, and these were the patients with less disease activity when compared with those who experienced a loss of treatment benefit. “The[se] observations should be taken with caution due to the small sample size; however, they provide some indication of potential disease characteristics of patients in whom long-term remission may be possible.”

BRAVE-AA1 included 654 patients (mean age 37.1 years, 58.6 percent female) with severe alopecia areata who received treatment with baricitinib at either 4 or 2 mg or placebo. At week 52, 39 and 115 patients who achieved treatment response with 2- and 4-mg baricitinib, respectively, were included in the withdrawal substudy and randomly assigned to continue with their initial baricitinib dose or to switch to placebo.

*Severity of Alopecia Tool