Baricitinib: 80% hair regrowth in 40% of alopecia areata patients NEJM Review

Alopecia areata is an autoimmune disease characterized by non-scarring alopecia that can affect areas such as the eyebrows and eyelash.
Moderate-to-severe alopecia areata requires treatment, but existing therapies such as glucocorticoids and other immunosuppressive agents have variable efficacy in severe alopecia area.
Cytokines involved in the pathogenesis of alopecia areata depend on Janus kinase (JAK) for intracellular signaling, and thus the JAK inhibitor baricitinib is being investigated for the treatment of alopecia area.
On May 5, 2022, the New England Journal of Medicine (NEJM) published two Phase 3 trials, BRAVE-AA1 and BRAVE-AA2, of oral baricitinib in the treatment of alopecia area.
The results showed that at week 36, baricitinib 4 The proportion of patients with 80% or more scalp hair coverage in the mg group was close to 40%, and the proportion of complete or almost complete regrowth of eyebrows and eyelashes was also close to 4
"NEJM Frontiers of Medicine" specially invited Professor Zhang Jianzhong from the Department of Dermatology, Peking University People's Hospital to interpret this resear.
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Li Xiangqian, Zhang Jianzhong, Department of Dermatology, Peking University People's Hospital Alopecia areata is an autoimmune inflammatory disease mainly mediated by T cells and targeting hair follicles in the growing peri.
Hair anywhere on the body [
Most mild alopecia areata (one or several small patches of hair loss) can be cured on their own, and some can rec.
If the hair loss area exceeds 25% of the scalp area, it is considered to be moderate to severe alopecia area.
In severe cases, all the hair is lost (alopecia totalis), and even all the hair on other parts of the body is lost (alopecia universali.
Moderate to severe alopecia areata can seriously affect the external image of patients, and patients are often prone to anxiety, depression and other emotio.
The disease is very common clinically, and there are currently about 147 million patients with alopecia areata worldwi.
Normal hair follicles are in a state of immune immuni.
In patients with alopecia areata, certain incentives lead to the destruction of the immune immunity of hair follicles, the activation of CD8+NKG2D+T cells, and the release of a large number of inflammatory factors (mainly IFN-γ) and cytokines, which cause hair follicle damage in the growth phase, which leads to hair lo.
[
In response to this main pathogenesis, for mild patients, topical or intralesional injection of glucocorticoids and topical minoxidil are often used in clinical treatme.

Moderate and severe patients often require oral glucocorticoids and immunomodulatory dru.

These treatments are very effecti.

The major limitation is that once the drug is discontinued, most patients with moderate to severe disease tend to repe.

Therefore, both dermatologists and patients are looking for a safe and effective non-hormonal treatment for alopecia area.

On March 26, 2022, the New England Journal of Medicine (NEJM) published online (officially published May 5) the results of two Phase 3 clinical trials of oral baricitinib in severe alopecia area.

, patients taking 2 mg/d and 4 mg/d baricitinib both met the primary efficacy endpoint after 36 weeks of dosing, compared with placebo, patients taking 2 mg/d and 4 mg/d baricitinib The number of hair regeneration increased significantly [
In the pathogenesis of alopecia areata, the JAK/STAT pathway plays an important ro.

JAK1/2 and JAK1/3 can promote the production of IFN-γ and IL-15 in the hair follicle, which can cascade the inflammatory response around the hair follicle[
Inhibiting the JAK/STAT pathway can inhibit the activation, proliferation and differentiation of CD8+ T cells around the hair follicle, thereby promoting hair regrowth, which is the main mechanism of action of JAK inhibitors in the treatment of alopecia area.

Baricitinib, a selective JAK1 and JAK2 inhibitor, was approved by the.


FDA in June 2018 for the treatment of moderate to severe rheumatoid arthritis
Approval in China is July 201With the in-depth study of the drug mechanism, its use in the treatment of severe atopic dermatitis has been approved in some countries and regio.

Indications currently under development include alopecia areata, ulcerative colitis, systemic lupus erythematosus, and juvenile idiopathic arthrit.

The research published by NEJM consists of two clinical trials, BRAVE-AA1 and BRAVE-AABRAVE-AA1 is a multicenter, randomized, double-blind, placebo-controlled, adaptive Phase 2/3 clinical trial of 1200 patients with severe alopecia areata (Severity of Hair Loss Tool [SALT] score ≥50,.


scalp Hair loss area is more than 50.

Based on the results of an interim analysis after 12 weeks of dosing published prior to Phase 2 of the BRAVE-AA1 trial, subsequent Phase 3 trials (BRAVE-AA1 Phase 3 and BRAVE-AA2) used baricitinib 2 mg Once-daily and 4 mg once-daily doses are administer.

The primary treatment endpoint was the proportion of patients achieving a SALT score of ≤20 (ie, 80% or more of scalp hair coverage) at week 3Results of the BRAVE-AA1 trial showed that the proportion of patients with a SALT score ≤20 at week 36 was: 38% in the baricitinib 4 mg group, 28% in the baricitinib 2 mg group, and 2% in the placebo gro.

Results of the BRAVE-AA2 trial The proportions of patients in the above groups were 39%, 14% and 3%, respectively (Figure
In addition, nearly 40% of patients in the baricitinib 4 mg dose group had complete or almost complete regrowth of eyebrows and eyelash.
FigureProportion of patients with SALT score ≤20 at 36 weeks of oral baricitinib ) included acne, upper respiratory tract infection, headache, urinary tract infection, elevated serum creatine kinase levels, and elevated low-density and high-density lipoprotein cholesterol levels, with no thromboembolic events (VTE.

The limitations of this trial include:Patients with severe alopecia areata with a history of more than 8 years without any hair regrowth and patients who had received oral JAK inhibitors and had poor efficacy were excluded, so it is unclear whether oral baricitinib is effective for these patientsAlthough the exclusion criteria included patients with androgenetic alopecia, there were still a small number (3%) of patients with alopecia areata who were using the same dose of androgenetic alopecia treatment drugs for a long time in this study, which may affect baricitinib Efficacy evaluation;Due to the outbreak of novel coronavirus pneumonia during the study period, part of the efficacy evaluation was conducted remotely, which was regarded as a missing item in the result analysis; both trials supplemented this deficiency by increasing the sample si.

The expansion phase of the trial is currently underway, and longer-term observations are required to further evaluate the potential delayed response of the drug, the durability of efficacy, and long-term safe.

In China, a phase 3 clinical trial of oral baricitinib for the treatment of severe adult alopecia areata is ongoi.

At the same time, JAK inhibitors independently developed by Chinese pharmaceutical companies are also undergoing phase 2 and 3 clinical studies, and more drugs are undergoing pre-trial approv.

These positive developments make us hopeful for the treatment of alopecia area.

Similar to other JAK inhibitors, recent studies have shown that long-term oral baricitinib has a good safety profile (median treatment 3 years, longest treatment time 3 years) [The.


FDA’s Boxed Warning for Adverse Reactions of JAK Inhibitors (serious cardiac events, cancer, coagulation, and death) is still a cautionary tale for dermatologists to safely use JAK inhibitors, and to deal with tuberculosis, hepatitis, tumors, cardiovascular The disease should be carefully screened, and patients should be followed up and reviewed regularly while taking the dr.
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Clin Rev Allergy Immunol 2021;61:403-42 King B, Ohyama M, Kwon O, et .

Two phase 3 trials of baricitinib for alopecia area.

N Engl J Med 2022;386:1687 -169 Divito SJ, Kupper .

Inhibiting Janus kinases to treat alopecia area.

Nat Med 2014;20:989-99 Taylor PC, Takeuchi T, Burmester GR, et .

Safety of baricitinib for the treatment of rheumatoid arthritis over a median of 6 and up to 3 years of treatment: final results from long-term extension study and integrated databa.

Ann Rheum Dis 2022;81:335-34 The author introduces Zhang Jianzhong, Chief Physician, Professor, .


, Department of Dermatology, Peking University People's Hospital Student tutor, national famous doct.
Chairman of the 13th Committee of the Dermatology Branch of the Chinese Medical Association, Chairman of the Dermatology Rehabilitation Professional Committee of the Chinese Association of Rehabilitation Medicine, Vice President of the Dermatology Branch of the Chinese Medical Doctor Association, Vice President of the Dermatology Branch of the Global Chinese Medical Doctor Association, Asia Director of the Academy of Dermatology (ADA), Chairman of the Chinese Hair Research Society (CHES), Head of the Trichology Group of the Dermatology Branch of the Chinese Medical Association, Director of the International Atopic Dermatitis Research Society, and Atopic Dermatitis of the Dermatology Branch of the Chinese Medical Association Chief expert of the research cent.

Editorial board member of Journal of American Academy of Dermatology, editor board member of Chinese Medical Journal, deputy editor-in-chief of "Chinese Journal of Dermatology", deputy editor-in-chief of "Chinese Journal of Dermatology and Venereology", and deputy editor-in-chief of "Journal of Clinical Dermatolog.

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