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HomeA FocusBRAVE trials show that baricitinib can slap down alopecia

BRAVE trials show that baricitinib can slap down alopecia

An oral Janus kinase (JAK) inhibitor produced significant, durable hair growth, including scalp, eyebrows, and eyelashes in patients with severe alopecia areata (AA), according to long-term data from two randomised trials, in the New England Journal of Medicine. The condition came under the most public of spotlights this week when Oscar-winning actor Will Smith slapped the presenter for joking about Smith’s wife Jada Pinkett’s alopecia.

An autoimmune diseases with no approved therapies, alopecia areata affects men and women alike and causes rapid hair loss in the scalp, eyebrows, and eyelashes.

The pathogenesis of the condition involves genetic and immune factors. The research team conducted the studies on the assumption that Eli Lilly’s Olumiant, which selectively inhibits JAK 1 and 2, may interrupt cytokine signalling involved in the pathogenesis of AA.

The research team enrolled 654 patients with severe AA in BRAVE-AA1 and 546 in BRAVE-AA2 whose severity of alopecia tool (SALT) scores were 50 or higher. The study compared Olumiant 4mg and 2mg with placebo. The primary outcome was a SALT score of 20 or less at week 36, and almost 30% had a SALT score of under 10.

Almost half of the patients had met response criteria for eyebrow and eyelash regrowth, reported Dr Brett King of Yale School of Medicine, lead author, at a presentation to the American Academy of Dermatology (AAD) meeting in Boston (25-29 March). The 52-week results showed continued improvement compared with results after 36 weeks of follow-up, which were reported simultaneously.

In BRAVE-AA1, the results showed that the percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg Olumiant, 22.8% with 2-mg Olumiant, and 6.2% with placebo. In BRAVE-AA2, the results were similar. The percentage of patients with a SALT score of 20 or less was 35.9%, 19.4%, and 3.3%.

More common adverse events (AEs) in the Olumiant group compared to the placebo arm were acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol.

“In two phase 3 trials involving patients with severe AA, oral baricitinib was superior to placebo concerning hair regrowth at 36 weeks,” the research team said. However, it added that longer studies are needed to assess the efficacy and safety of baricitinib for AA.

“Continued treatment with baricitinib after 36 weeks resulted in further increases in the proportion of patients who achieved scalp, eyebrow, and eyelash hair regrowth,” said King. “The proportion of patients achieving a SALT score <20 and/or a SALT score <10 – and that’s kind of a high bar – continued to increase. The proportion of patients achieving ClinRO [Clinician Reported Outcome] for eyebrow and eyelash hair loss also continued to increase, restoring to nearly normal or normal.

“This is truly transformational for patients,” King said. “These patients start out looking nothing like themselves, and when they finish, at least when it works, looking like themselves again, restored to normal.”

Limited treatment options

The study population had a median age of about 37, and women accounted for about 60% of all patients. About two-thirds of the patients had an alopecia duration of under 4 years, and more than 40% had alopecia universalis. Baseline SALT score averaged about 85 across the placebo and baricitinib groups.

King said patients with longstanding alopecia areata are not good candidates for treatment with the JAK inhibitor. A patient with a 10-year history of the hair loss is unlikely to benefit, although outliers do exist.

Similar results emerged from a subgroup analysis of phase IIb/III placebo-controlled study of a different JAK inhibitor. An analysis of 105 adolescents (mean age 15) included in the overall study population showed that the JAK3/TEC inhibitor ritlecitinib led to SALT score ≤20 responses in 17%-28% of patients treated for 24 weeks with one of five doses of the drug. Additionally, 17%-28% of patients met criteria for SALT ≤10 responses.

From 22%-61% of patients treated with ritlecitinib rated results as improved or much improved on Patient Global Impression of Change index. The best results occurred in patients randomised to a 200-mg loading dose of the drug followed by 50 or 30 mg daily, reported Dr Maria Hordinsky of the University of Minnesota in Minneapolis, and colleagues, in an AAD poster presentation. The most common AEs (including the placebo group) were headache, nasopharyngitis, and upper respiratory infection.

Ritlecitinib earned an FDA Breakthrough Therapy designation in September 2018 for alopecia areata, while baricitinib is currently FDA approved for the treatment of adults with moderate-to-severe active rheumatoid arthritis, and as a treatment for COVID-19 with remdesivir (Veklury), per a 2020 FDA Emergency Use Authorization.

Study details
Two Phase 3 Trials of Baricitinib for Alopecia Areata

Brett King, Manabu Ohyama, Ohsang Kwon, Abraham Zlotogorski, Justin Ko, Natasha A. Mesinkovska, Maria Hordinsky, Yves Dutronc, Wen-Shuo Wu, Jill McCollam, Chiara Chiasserini, Guanglei Yu, et al.

Published in New England Journal of Medicine on 26 March 2022

Abstract

Background
Alopecia areata is an autoimmune condition characterised by rapid hair loss in the scalp, eyebrows, and eyelashes, for which treatments are limited. Baricitinib, an oral, selective, reversible inhibitor of Janus kinases 1 and 2, may interrupt cytokine signalling implicated in the pathogenesis of alopecia areata.

Methods
We conducted two randomised, placebo-controlled, phase 3 trials (BRAVE-AA1 and BRAVE-AA2) involving adults with severe alopecia areata with a Severity of Alopecia Tool (SALT) score of 50 or higher (range, 0 [no scalp hair loss] to 100 [complete scalp hair loss]). Patients were randomly assigned in a 3:2:2 ratio to receive once-daily baricitinib at a dose of 4 mg, baricitinib at a dose of 2 mg, or placebo. The primary outcome was a SALT score of 20 or less at week 36.

Results
We enrolled 654 patients in the BRAVE-AA1 trial and 546 in the BRAVE-AA2 trial. The estimated percentage of patients with a SALT score of 20 or less at week 36 was 38.8% with 4-mg baricitinib, 22.8% with 2-mg baricitinib, and 6.2% with placebo in BRAVE-AA1 and 35.9%, 19.4%, and 3.3%, respectively, in BRAVE-AA2. In BRAVE-AA1, the difference between 4-mg baricitinib and placebo was 32.6 percentage points (95% confidence interval [CI], 25.6 to 39.5), and the difference between 2-mg baricitinib and placebo was 16.6 percentage points (95% CI, 9.5 to 23.8) (P<0.001 for each dose vs. placebo). In BRAVE-AA2, the corresponding values were 32.6 percentage points (95% CI, 25.6 to 39.6) and 16.1 percentage points (95% CI, 9.1 to 23.2) (P<0.001 for each dose vs. placebo). Secondary outcomes for baricitinib at a dose of 4 mg but not at a dose of 2 mg generally favored baricitinib over placebo. Acne, elevated levels of creatine kinase, and increased levels of low- and high-density lipoprotein cholesterol were more common with baricitinib than with placebo.

Conclusions
In two phase 3 trials involving patients with severe alopecia areata, oral baricitinib was superior to placebo with respect to hair regrowth at 36 weeks. Longer trials are required to assess the efficacy and safety of baricitinib for alopecia areata.

 

AAD Poster Presentation by Dr Maria Hordinsky
The need for, development and initial validation of the Scale of Alopecia Areata Distress, a brief survey to assess Alopecia Areata patient-reported psychosocial outcomes

Kristina Gorbatenko-Roth, Sarah Wood, Denise Windenburg, Irmina Wallander, and Maria Hordinsky.

Abstract

Losing one’s hair doesn’t usually physically ‘hurt’; it’s the psychological and social consequences of the hair loss which often are most painful.1-7 To be deemed effective by patients, clinicians, and payers approving coverage for treatments, any new Alopecia Areata (AA) treatment needs to address, and help reduce, this psychosocial disease burden.8,9 To demonstrate such treatment benefit, a psychometrically validated scale of AA psychosocial Patient Reported Outcomes (PRO) is required.10 Currently, no such scale is publicly known to exist (Dory Kranz, former CEO of the National Alopecia Areata Foundation [NAAF], personal communication, January 9, 2020). The purpose of the study was to develop and begin psychometric validation of a brief scale assessing the psychosocial disease burden of AA, the Scale of Alopecia Areata Distress (SAAD).

To develop the SAAD, potential survey questions were constructed for each previously identified domain of psychosocial PRO.10 The resulting 142-item pool was then reviewed for relevance and comprehensiveness by 5 experts in AA disease burden: dermatologists with AA expertise, AA patients serving as NAAF support group leaders, and NAAF staff. Based upon expert-review, the item pool was reduced to 122 questions and patient pilot tested.

The final 122 questions were administered to over 300 adult US-based participants with AA, recruited through NAAF and a tertiary hair disease clinic at the University of Minnesota. Results from an exploratory factor analysis and internal consistency reliability assessment will be shared, as will the final questions on the brief SAAD scale.

 

New England Journal of Medicine article – Two Phase 3 Trials of Baricitinib for Alopecia Areata (Restricted access)

 

AAD poster presentation – The need for, development and initial validation of the Scale of Alopecia Areata Distress, a brief survey to assess Alopecia Areata patient-reported psychosocial outcomes (Open access)

 

AAD Annual Meeting 2022 (Open access)

 

See more from MedicalBrief archives:

 

High doses of hormone drug linked to meningioma risk – Meta-analysis

 

Opzelura: FDA approves first topical JAK inhibitor for atopic dermatitis

 

Osteoporosis drug found to stimulate hair follicle growth

 

Medicine mix-up causes 'werewolf syndrome' in Spanish children

 

 

 

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