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For patients with severe alopecia areata who had meaningful hair regrowth after 1 year of oral baricitinib (Olumiant) therapy, treatment withdrawal resulted in loss of benefit in almost all patients, indicating that continued therapy is needed, a substudy of the randomized BRAVE-AA1 trial showed.

At week 152, 80% of patients taking baricitinib 2 mg or 4 mg had lost benefit -- a >20-point worsening in Severity of Alopecia Tool (SALT) score -- compared with 7% of those who continued treatment in both dose groups, reported Brett King, MD, PhD, of Yale School of Medicine in New Haven, Connecticut, and colleagues.

During the follow-up observation periods, 63% of patients taking 2-mg baricitinib and 87.5% of those taking 4-mg baricitinib achieved a SALT score of 20 or less after retreatment, they noted in .

"Therefore, it is not recommended to discontinue therapy after achieving successful regrowth with 1 year of therapy," the researchers concluded. "Treatment withdrawal was dictated by the clinical trial design, which was distinctly different from clinical practice, in which the duration and/or depth of response and other parameters (baseline disease severity or chronicity) broadly inform treatment decisions, but may be especially important in guiding decisions to adjust the dose, interrupt therapy, or discontinue treatment."

Results from the BRAVE-AA1 and BRAVE-AA2 trials previously showed that almost 40% of patients achieved a SALT score ≤20 at 52 weeks with the higher dose of the oral Janus kinase (JAK) inhibitor, and almost 30% had a SALT score ≤10. In June 2022, the FDA approved baricitinib as the first systemic treatment for alopecia areata.

Shoshana Marmon, MD, PhD, of New York Medical College in Valhalla, told 乌鸦传媒 that this substudy "provides insights into which characteristics may influence the potential for successful treatment withdrawal."

"Patients who had a shorter duration of their current alopecia areata episode, a shorter period prior to disease onset, no loss of eyebrows or eyelashes, and the absence of atopy and alopecia universalis were more likely to sustain hair regrowth after treatment withdrawal," she said. "Less severe baseline characteristics and shorter disease duration were also correlated with better maintenance of treatment response."

King and co-authors cited the recommendation from the that discontinuation of systemic treatment be considered "only after complete regrowth has been achieved and maintained for 6 months or when it is sufficient to be managed with topical treatments."

"It is uncertain what the loss of treatment benefit would have been in the present study had patients been required to achieve full and stable regrowth of scalp hair for at least 6 months before treatment withdrawal," they added.

Cathryn Sibbald, MD, MSc, of the University of Toronto, noted that "most patients are far too worried about new hair loss to want to stop treatment."

"In those who need to stop (loss of coverage, pregnancy), we can at least refer to these data to show that they may lose hair over 6-12 months, but could recapture their success if they are able to restart," she told 乌鸦传媒. "In patients who want to stop but don't need to, I like the approach of an extremely slow taper with close monitoring for new loss."

Rod Sinclair, MBBS, MD, of the University of Melbourne in Australia, who was a co-author for both the expert consensus recommendations and the original BRAVE trials, told 乌鸦传媒 that "the question is what is different about JAK inhibitors where treatment withdrawal leads to near universal relapse, while only 50% relapse with systemic steroid withdrawal."

The different durability of response could relate to patient selection, Sinclair explained. "In this study, many baricitinib responders were slow responders, [thus] withdrawal may have been premature. Withdrawal was often abrupt and not tapered as would occur with systemic steroids. The real-world question is how to best support when baricitinib is withdrawn in our patients."

The phase III BRAVE-AA1 study was conducted at 70 centers in three countries beginning in March 2019. It included 654 adults with severe alopecia areata (SALT score ≥50) who were randomized 3:2:2 to receive treatment with baricitinib 4 mg, baricitinib 2 mg, or placebo. Mean age was 37, and 58.6% were women.

At week 52, 154 patients who were responders (SALT score ≤20) were re-randomized 3:1 to continue with their current baricitinib dose or transition to placebo. Those randomized to placebo who experienced a loss of treatment benefit at any time after week 52 were retreated with their original baricitinib dose.

At 4 and 8 weeks of treatment withdrawal, 0% and 10-11% of patients, respectively, lost treatment benefit regardless of dose.

Study limitations included possible delays in retreatment, leaving insufficient time for response, and "a small but clinically important risk that some patients may not show a response to retreatment," King and colleagues wrote.

Arash Mostaghimi, MD, MPH, of Brigham and Women's Hospital in Boston, told 乌鸦传媒 that "future research needs to focus on predictive models to determine which patients are at highest risk -- these same data show that you can likely safely stop the medication in one out of five patients, and it would be great to know who those patients are a priori."

"Replication of this study in a real-world setting, where most people would not stop baricitinib unless SALT is <5 and very stable, would be of benefit, as would evaluation of the impact of concomitant therapeutics such as low-dose minoxidil on hair maintenance after JAK discontinuation," he said.

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