For patients with severe alopecia areata who experienced significant hair growth after one year of oral baricitinib (Olumiant) treatment, treatment discontinuation resulted in nearly all patients losing benefit, indicating the need for continued treatment. , presented a substudy of the randomized BRAVE-AA1 trial.
As of week 152, 80% of patients receiving baricitinib 2 mg or 4 mg had lost efficacy and had lower Alopecia Severity Tool (SALT) scores compared with 7% of patients who continued treatment in both dose groups. worsened by more than 20 points. , Brett King, MD, PhD, of Yale University School of Medicine in New Haven, Connecticut, and colleagues reported.
During the follow-up period, 63% of patients taking baricitinib 2 mg and 87.5% of patients taking baricitinib 4 mg achieved a SALT score of 20 or less after retreatment, the researchers wrote in JAMA Dermatology.
“Therefore, discontinuing treatment after 1 year of successful regrowth is not recommended,” the researchers concluded. “Treatment discontinuation is determined by the clinical trial design, which clearly differs from clinical practice, in which the duration and depth of response and other parameters (such as baseline disease severity and chronicity) are determined. ) broadly influence treatment decisions, but may be particularly important in guiding decisions about adjusting dosage, interrupting treatment, or discontinuing treatment. ”
Results from the BRAVE-AA1 and BRAVE-AA2 trials showed that when given higher doses of oral Janus kinase (JAK) inhibitors, nearly 40% of patients achieved a SALT score of 20 or less at 52 weeks, and almost 30% It shows you achieved your 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 at Valhalla, told MedPage Today that this sub-study “provides insight into which characteristics may influence the likelihood of successful treatment withdrawal.” he said.
“Patients with current alopecia areata who have a short onset period, a short time to disease onset, no loss of eyebrows or eyelashes, and no atopic dermatitis or alopecia universalis will maintain hair regrowth even after treatment is discontinued. “It was more likely,” she said. Said. “Less severe baseline characteristics and shorter disease duration also correlated with better maintenance of treatment response.”
King et al. cite the Alopecia Areata Expert Consensus recommendation that systemic treatment should be discontinued “after complete regrowth has been achieved and maintained for 6 months, or when topical treatment is sufficient. “Only these should be considered.”
“It is unclear how much of the treatment effect would have been lost in this study if patients had been required to achieve complete and stable regrowth of scalp hair for at least six months before discontinuing treatment.” the researchers added.
“Most patients are too worried about new hair loss to want to stop treatment,” said Kathryn Sibbald, MD, MSc, of the University of Toronto.
“For people who need to stop (loss of insurance coverage, pregnancy), at least look at these data and know that they may lose hair over a 6-12 month period, but that if they can restart, they can regain success.” ” she said. he told MedPage Today. “For patients who want to stop but don’t need to, I like the approach of tapering very slowly while closely monitoring new losses.”
Rod Sinclair, MD, MBBS, of the University of Melbourne, Australia, co-author of the expert consensus recommendations and the original BRAVE trial, told MedPage Today: “The question is how different are the JAK inhibitors when treatment is discontinued?” Only 50% of patients relapse after systemic steroid withdrawal, but nearly all do. ”
The difference in durability of response may be related to patient selection, Dr. Sinclair explained. “In this study, many of the people who were slow to respond to baricitinib had a slow response and may have withdrawn prematurely. Withdrawal was often sudden and did not taper as with systemic steroids. The real world question is how best to support them in the event of baricitinib withdrawal.” ”
The Phase III BRAVE-AA1 trial was conducted at 70 sites in three countries starting in March 2019. The study 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. The average age was 37 years, and 58.6% were female.
At week 52, 154 patients who were responders (SALT score ≤20) were re-randomized 3:1 to continue on their current baricitinib dose or go to placebo. Patients randomized to placebo who experienced a loss of treatment effect at any time after week 52 were readministered at their original baricitinib dose.
At 4 and 8 weeks after discontinuing treatment, 0% and 10-11% of patients, respectively, lost the benefit of treatment, regardless of dose.
Limitations of the study include the possibility of delayed retreatment and insufficient time to response, “a small but clinically important risk that some patients may not respond to retreatment.” Professor King et al.
“Future research needs to focus on predictive models to determine which patients are at highest risk,” Arash Mostaghimi, MD, MPH, of Brigham and Women’s Hospital in Boston, told MedPage Today. These same data indicate that it is likely that the medication can be stopped safely.” One in five patients do, and it would be great to know a priori who those patients are. ”
“Replicating this study in a real-world setting, where most people would not discontinue baricitinib unless their SALT is <5 and very stable, will likely impact the hair effects of combination treatments such as low-dose minoxidil." It will be beneficial as well as the evaluation of ``JAK post-discontinuation maintenance,'' he said.
Kate Kneisel is a freelance medical journalist based in Belleville, Ontario.
disclosure
Eli Lilly and Company, the manufacturer of baricitinib, participated in the study.
Mr. King reported receiving personal compensation from Eli Lilly, Sun, and Pfizer, and his spouse served as a consultant, speaker, and advisory board member for Pfizer, Eli Lilly, and Sun. was serving.
The co-authors also reported relationships with industry such as Eli Lilly.
Mr. Marmon reported no conflicts of interest.
Mr. Sibbald reported receiving honoraria from AbbVie, Novartis, Pfizer, UCB, Leo Pharma, and Sanofi.
Mr. Sinclair is a director and founder of Samsung Medical Technologies and holds a patent for the use of oral minoxidil in the treatment of hair loss disorders. He also works with Eli Lilly, Pfizer, Reopharma, AbbVie, Novartis, GSK, Amgen, Arctis Biotherapeutics, Aerotech, Merck, Celgene, CoHealth Biosciences, Janssen, Regeneron, MedImmune, Boehringer Ingelheim, Oncobiologics, Roche, Ascend, Dermira, AstraZeneca, Akeso, Lystone Biopharma, UCB, Sanofi, Connect, Arena, Sun Pharma, Bristol-Myers Squibb, Botanix Pharmaceuticals, Zai Pharmaceuticals, Jiangsu Hengrui Pharmaceutical, Galderma.
Mr. Mostaghimi is a member of AbbVie, Him’s & Hers Health, Sun Pharma, Pfizer, Digital Diagnostics, Lilly, Equillium, Aslan Pharmaceuticals, Boehringer Ingelheim, Figure 1, Acom Healthcare, Ola Plex, reported receiving personal fees from Legacy Healthcare.
primary source
JAMA Dermatology
Reference source: King B et al. “Baricitinib discontinuation and retreatment in patients with severe alopecia areata: BRAVE-AA1 randomized clinical trial” JAMA Dermatol 2024; DOI: 10.1001/jamadermatol.2024.2734.
