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Two Phase 3 Trials of Baricitinib for Alopecia Areata

List of authors.
  • Brett King, M.D., Ph.D.,
  • Manabu Ohyama, M.D., Ph.D.,
  • Ohsang Kwon, M.D., Ph.D.,
  • Abraham Zlotogorski, M.D.,
  • Justin Ko, M.D.,
  • Natasha A. Mesinkovska, M.D., Ph.D.,
  • Maria Hordinsky, M.D.,
  • Yves Dutronc, M.D.,
  • Wen-Shuo Wu, M.D.,
  • Jill McCollam, Pharm.D.,
  • Chiara Chiasserini, Sc.D.,
  • Guanglei Yu, Ph.D.,
  • Sarah Stanley, Ph.D.,
  • Katrin Holzwarth, M.D.,
  • Amy M. DeLozier, M.P.H.,
  • and Rodney Sinclair, M.D.
  • for the BRAVE-AA Investigators*

Abstract

Background

Alopecia areata is an autoimmune condition characterized 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 signaling implicated in the pathogenesis of alopecia areata.

Methods

Download a PDF of the Research Summary.

We conducted two randomized, 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. (Funded by Eli Lilly under license from Incyte; BRAVE-AA1 and BRAVE-AA2 ClinicalTrials.gov numbers, NCT03570749 and NCT03899259.)

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Funding and Disclosures

Supported by Eli Lilly under license from Incyte.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on March 26, 2022, at NEJM.org.

A data sharing statement provided by the authors is available with the full text of this article at NEJM.org.

We thank all the patients and trial staff who participated in these trials. Medical writing and editorial support were provided by Amy K. Ellinwood, Ph.D., and Fionn T. McSwiney, Ph.D., of Eli Lilly.

Author Affiliations

From the Yale School of Medicine, New Haven, CT (B.K.); the Department of Dermatology, Kyorin University Faculty of Medicine, Tokyo (M.O.); the Seoul National University College of Medicine, Seoul, South Korea (O.K.); the Department of Dermatology, Hadassah Medical Center, Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem, Israel (A.Z.); Stanford University School of Medicine, Stanford (J.K.), and the University of California Irvine, Irvine (N.A.M.) — both in California; the Department of Dermatology, University of Minnesota Medical School, Minneapolis (M.H.); Eli Lilly, Indianapolis (Y.D., W.-S.W., J.M., C.C., G.Y., S.S., K.H., A.M.D.); and Sinclair Dermatology, Melbourne, VIC, Australia (R.S.).

Dr. King can be contacted at or at the Department of Dermatology, Yale School of Medicine, 333 Cedar St., LCI 501, P.O. Box 208059, New Haven, CT 06510.

The BRAVE-AA Investigators are listed in the Supplementary Appendix, available at NEJM.org.

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