Baricitnib Withdrawal Leads to Loss of Benefit in Up to 80% with Alopecia Areata

Brett King, MD, PhD
Credit: Yale Dermatology

New data from the BRAVE-AA program is underlining the importance of continued therapy with baricitinib (Olumiant) among patients with severe alopecia areata.

A substudy of the trial examining withdrawal and retreatment rates from the BRAVE-AA1 trial, indicate 80% of patients who discontinue treatment experience a loss of treatment benefit, regardless of dose, 100 weeks after stopping treatment with the oral janus kinase inhibitor.¹

“In patients with severe [alopecia areata], withdrawal of therapy among patients who achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in almost all patients losing their hair. Therefore, it is not recommended to discontinue therapy after achieving successful regrowth with 1 year of therapy (52 weeks),” wrote investigators.¹ “These data add to our growing knowledge of severe [alopecia areata], showing that it is a chronic disease and similar to other autoimmune diseases and requires long-term maintenance therapy for most patients to maintain successful outcomes.”

Developed and marketed through a partnership between Eli Lilly and Company and Incyte, baricitinib made history in 2022 when it became the first systemic therapy to receive approval for alopecia areata based on data from the BRAVE-AA program, which included the BRAVE-AA1 and BRAVE-AA2 trials. Though both trials examined the therapy in patients with severe alopecia areata, BRAVE-AA1 was a randomized, double-blind, placebo-controlled adaptive trial and BRAVE-AA2 was a randomized, double-blind, placebo-controlled study.^1,2

The BRAVE-AA1 trial had a primary outcome of interest of proportion of patients achieving a Severity of Alopecia Tool [SALT] score of 20 or less at week 36. Results of the trial indicated the endpoint was achieved by 35% (P <.001), 22% (P <.001), and 5% of the baricitinib 4 mg, baricitinib 2 mg, and placebo groups, respectively.³

As part of the design, BRAVE-AA1 included a withdrawal substudy. This substudy rerandomized responders to baricitinib in a 3:1 ratio to continue treatment or to transition to placebo. The primary outcome of interest for the substudy was the proportion of patients who lost treatment benefit through week 152 and the proportion of patients who recaptured response after retreatment.¹

A total of 115 patients receiving baricitinib met inclusion criteria for the substudy at 52 weeks. Per trial protocol, responders rerandomized to placebo who experienced a loss of treatment benefit, which was defined as 20-point or greater worsening in SALT score, were rerandomized to their original baricitinib dose.¹

Results of the substudy suggested 0% and 10% to 11% of patients lost treatment benefit regardless of dose at 4 and 8 weeks of treatment withdrawal, respectively. The primary outcome analyses at week 152 indicted 80% of patients rerandomized to placebo had lost benefit. In contrast, only 7% of those who continued baricitinib therapy experienced lost benefit. Investigators also highlighted 63% of the baricitinib 2 mg group and 87.5% of the baricitinib 4 mg group achieved a SALT score of 20 or less response after retreatment.¹

“Severe [alopecia areata] is a chronic, relapsing condition, and this randomized clinical trial found that withdrawal of therapy for a patient population with severe [alopecia areata] who had achieved meaningful hair regrowth after 1 year of treatment with baricitinib resulted in loss of benefit for almost all patients, indicating that continued therapy is required to maintain hair regrowth,” investigators added.¹

References:

1. King B, Ko J, Kwon O, et al. Baricitinib Withdrawal and Retreatment in Patients With Severe Alopecia Areata: The BRAVE-AA1 Randomized Clinical Trial. JAMA Dermatol. Published online August 14, 2024. doi:10.1001/jamadermatol.2024.2734
2. Eli Lilly and Company. FDA approves Lilly and Incyte’s OLUMIANT® (baricitinib) as First and only systemic medicine for adults with severe alopecia areata. Eli Lilly and Company. June 13, 2022. Accessed August 14, 2024. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lilly-and-incytes-olumiantr-baricitinib-first-and.
3. Eli Lilly and Company. Lilly and Incyte’s baricitinib improved hair regrowth for alopecia areata patients in Second phase 3 study. Eli Lilly and Company. April 20, 2021. Accessed August 14, 2024. https://investor.lilly.com/news-releases/news-release-details/lilly-and-incytes-baricitinib-improved-hair-regrowth-alopecia.