Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study

Elise A. Olsen; Deanna Kornacki; Kang Sun; Maria K. Hordinsky

doi:10.1016/j.jaad.2019.10.016

Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study

Elise A. Olsen
, Deanna Kornacki
, Kang Sun
, Maria K. Hordinsky

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

Abstract

Background: There are currently no treatments for alopecia areata (AA) that are universally effective or approved by the US Food and Drug Administration. Oral ruxolitinib has shown efficacy in extensive AA. Ruxolitinib cream would potentially avoid systemic adverse effects. Objective: To assess the efficacy and safety of 1.5% ruxolitinib cream in patients with AA who had at least 25% hair loss by Severity of Alopecia Tool score. Methods: This was a 2-part study. Part A was an open-label, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 99% hair loss followed by a 24-week extension period. Part B was a double-blind, vehicle-controlled, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 100% hair loss, followed by a crossover to ruxolitinib cream in the vehicle group for 24 weeks and additional treatment time for the ruxolitinib cream group. Results: Although Part A results suggested potential efficacy of 1.5% ruxolitinib cream, there was no significant difference in hair regrowth based on 50% improvement in Severity of Alopecia Tool scores between patients receiving 1.5% ruxolitinib cream and vehicle in part B. There were no significant safety issues with 1.5% ruxolitinib cream. Limitations: Single strength of ruxolitinib cream. Conclusions: The 1.5% ruxolitinib cream did not have a significant effect in patients with AA.

Original language	English (US)
Pages (from-to)	412-419
Number of pages	8
Journal	Journal of the American Academy of Dermatology
Volume	82
Issue number	2
DOIs	https://doi.org/10.1016/j.jaad.2019.10.016
State	Published - Feb 2020

Bibliographical note

Funding Information:
AA is an autoimmune type of hair loss characterized pathologically by a CD8 + /natural killer group 2D (NKG2D) lymphocytic infiltrate surrounding the hair bulb 17 before a transition from a robust anagen hair to an affected hair trapped in a prolonged telogen or early anagen phase. Mechanistically, the hair loss may involve upregulation of IL-15 and interferon gamma, which are decreased by inhibitors of the JAK/signal transducer and activator of transcription pathway. Animal models of AA have shown regrowth with topical JAK inhibitors, 13 and 0.6% ruxolitinib cream in patients with AU showed nearly full eyebrow and 10% scalp regrowth after 12 weeks of twice-daily treatment. 25 Our current study did not show a significant effect of 1.5% ruxolitinib cream in AA. This is reminiscent of topical tacrolimus, which exhibited promising efficacy in Dundee experimental bald rats but did not induce terminal hair regrowth in patients with AA, possibly due to insufficient penetration. 26 , 27 A topical formulation remains the ideal treatment for otherwise healthy AA patients ranging from young children to vulnerable elderly patients. The authors thank the patients and their families, investigators, coinvestigators, and clinical site staff involved in this study. Investigators included Wilma Bergfeld, MD, Cleveland Clinic, Cleveland, OH; Suzanne Bruce, MD, Suzanne Bruce and Associates, PA, Katy, TX; Janet C. Dubois, MD, DermResearch, Inc, Austin, TX; Boni Elewski, MD, University of Alabama, Birmingham, AL; David S. Greenstein, MD, ActivMed Practices & Research, Inc, Beverly, MA; Fasahat H. Hamzavi, MD, Hamzavi Dermatology, Fort Gratiot, MI; Maria K. Hordinsky, MD, University of Minnesota, Minneapolis, MN; Steven E. Kempers, MD, Minnesota Clinical Study Center, Fridley, MN; Brett King, MD, PhD, Church Street Research Unit, New Haven, CT; Amy J. McMichael, MD, Wake Forest University Health Sciences, Winston Salem, NC; Joseph Merola, MD, MMSc, Brigham and Women's Hospital, Boston, MA; Jeremy E. Moss, MD, PhD, New England Research Associates, LLC, Trumbull, CT; Janet Roberts, MD, Northwest Dermatology and Research Center, LLC, Portland, OR; David Rosmarin, MD, Tufts Medical Center, Boston, MA; Daniel Mitchel Stewart, DO, Michigan Center for Skin Care Research, Clinton Township, MI; Dowling B. Stough, MD, Burke Pharmaceutical Research, Hot Springs, AR; and Antonella Tosti, MD, University of Miami Hospital, Miami, FL. We also thank Dr Rich Leff for his contributions to the planning, facilitation, and analysis of this study. Editorial assistance was provided by Tania Iqbal, PhD, at Complete Healthcare Communications, LLC, an ICON plc company (North Wales, PA), whose work was funded by Incyte Corporation (Wilmington, DE).

Publisher Copyright:
© 2019 American Academy of Dermatology, Inc.

Keywords

alopecia areata
clinical trial
ruxolitinib cream

PubMed: MeSH publication types

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial

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10.1016/j.jaad.2019.10.016

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@article{0fc2ed2ade5847a2adaed75846ed014e,

title = "Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study",

abstract = "Background: There are currently no treatments for alopecia areata (AA) that are universally effective or approved by the US Food and Drug Administration. Oral ruxolitinib has shown efficacy in extensive AA. Ruxolitinib cream would potentially avoid systemic adverse effects. Objective: To assess the efficacy and safety of 1.5\% ruxolitinib cream in patients with AA who had at least 25\% hair loss by Severity of Alopecia Tool score. Methods: This was a 2-part study. Part A was an open-label, 24-week study of 1.5\% ruxolitinib cream in patients with 25\% to 99\% hair loss followed by a 24-week extension period. Part B was a double-blind, vehicle-controlled, 24-week study of 1.5\% ruxolitinib cream in patients with 25\% to 100\% hair loss, followed by a crossover to ruxolitinib cream in the vehicle group for 24 weeks and additional treatment time for the ruxolitinib cream group. Results: Although Part A results suggested potential efficacy of 1.5\% ruxolitinib cream, there was no significant difference in hair regrowth based on 50\% improvement in Severity of Alopecia Tool scores between patients receiving 1.5\% ruxolitinib cream and vehicle in part B. There were no significant safety issues with 1.5\% ruxolitinib cream. Limitations: Single strength of ruxolitinib cream. Conclusions: The 1.5\% ruxolitinib cream did not have a significant effect in patients with AA.",

keywords = "alopecia areata, clinical trial, ruxolitinib cream",

author = "Olsen, \{Elise A.\} and Deanna Kornacki and Kang Sun and Hordinsky, \{Maria K.\}",

note = "Funding Information: AA is an autoimmune type of hair loss characterized pathologically by a CD8 + /natural killer group 2D (NKG2D) lymphocytic infiltrate surrounding the hair bulb 17 before a transition from a robust anagen hair to an affected hair trapped in a prolonged telogen or early anagen phase. Mechanistically, the hair loss may involve upregulation of IL-15 and interferon gamma, which are decreased by inhibitors of the JAK/signal transducer and activator of transcription pathway. Animal models of AA have shown regrowth with topical JAK inhibitors, 13 and 0.6\% ruxolitinib cream in patients with AU showed nearly full eyebrow and 10\% scalp regrowth after 12 weeks of twice-daily treatment. 25 Our current study did not show a significant effect of 1.5\% ruxolitinib cream in AA. This is reminiscent of topical tacrolimus, which exhibited promising efficacy in Dundee experimental bald rats but did not induce terminal hair regrowth in patients with AA, possibly due to insufficient penetration. 26 , 27 A topical formulation remains the ideal treatment for otherwise healthy AA patients ranging from young children to vulnerable elderly patients. The authors thank the patients and their families, investigators, coinvestigators, and clinical site staff involved in this study. Investigators included Wilma Bergfeld, MD, Cleveland Clinic, Cleveland, OH; Suzanne Bruce, MD, Suzanne Bruce and Associates, PA, Katy, TX; Janet C. Dubois, MD, DermResearch, Inc, Austin, TX; Boni Elewski, MD, University of Alabama, Birmingham, AL; David S. Greenstein, MD, ActivMed Practices \& Research, Inc, Beverly, MA; Fasahat H. Hamzavi, MD, Hamzavi Dermatology, Fort Gratiot, MI; Maria K. Hordinsky, MD, University of Minnesota, Minneapolis, MN; Steven E. Kempers, MD, Minnesota Clinical Study Center, Fridley, MN; Brett King, MD, PhD, Church Street Research Unit, New Haven, CT; Amy J. McMichael, MD, Wake Forest University Health Sciences, Winston Salem, NC; Joseph Merola, MD, MMSc, Brigham and Women's Hospital, Boston, MA; Jeremy E. Moss, MD, PhD, New England Research Associates, LLC, Trumbull, CT; Janet Roberts, MD, Northwest Dermatology and Research Center, LLC, Portland, OR; David Rosmarin, MD, Tufts Medical Center, Boston, MA; Daniel Mitchel Stewart, DO, Michigan Center for Skin Care Research, Clinton Township, MI; Dowling B. Stough, MD, Burke Pharmaceutical Research, Hot Springs, AR; and Antonella Tosti, MD, University of Miami Hospital, Miami, FL. We also thank Dr Rich Leff for his contributions to the planning, facilitation, and analysis of this study. Editorial assistance was provided by Tania Iqbal, PhD, at Complete Healthcare Communications, LLC, an ICON plc company (North Wales, PA), whose work was funded by Incyte Corporation (Wilmington, DE). Publisher Copyright: {\textcopyright} 2019 American Academy of Dermatology, Inc.",

year = "2020",

month = feb,

doi = "10.1016/j.jaad.2019.10.016",

language = "English (US)",

volume = "82",

pages = "412--419",

journal = "Journal of the American Academy of Dermatology",

issn = "0190-9622",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - Ruxolitinib cream for the treatment of patients with alopecia areata

T2 - A 2-part, double-blind, randomized, vehicle-controlled phase 2 study

AU - Olsen, Elise A.

AU - Kornacki, Deanna

AU - Sun, Kang

AU - Hordinsky, Maria K.

N1 - Funding Information: AA is an autoimmune type of hair loss characterized pathologically by a CD8 + /natural killer group 2D (NKG2D) lymphocytic infiltrate surrounding the hair bulb 17 before a transition from a robust anagen hair to an affected hair trapped in a prolonged telogen or early anagen phase. Mechanistically, the hair loss may involve upregulation of IL-15 and interferon gamma, which are decreased by inhibitors of the JAK/signal transducer and activator of transcription pathway. Animal models of AA have shown regrowth with topical JAK inhibitors, 13 and 0.6% ruxolitinib cream in patients with AU showed nearly full eyebrow and 10% scalp regrowth after 12 weeks of twice-daily treatment. 25 Our current study did not show a significant effect of 1.5% ruxolitinib cream in AA. This is reminiscent of topical tacrolimus, which exhibited promising efficacy in Dundee experimental bald rats but did not induce terminal hair regrowth in patients with AA, possibly due to insufficient penetration. 26 , 27 A topical formulation remains the ideal treatment for otherwise healthy AA patients ranging from young children to vulnerable elderly patients. The authors thank the patients and their families, investigators, coinvestigators, and clinical site staff involved in this study. Investigators included Wilma Bergfeld, MD, Cleveland Clinic, Cleveland, OH; Suzanne Bruce, MD, Suzanne Bruce and Associates, PA, Katy, TX; Janet C. Dubois, MD, DermResearch, Inc, Austin, TX; Boni Elewski, MD, University of Alabama, Birmingham, AL; David S. Greenstein, MD, ActivMed Practices & Research, Inc, Beverly, MA; Fasahat H. Hamzavi, MD, Hamzavi Dermatology, Fort Gratiot, MI; Maria K. Hordinsky, MD, University of Minnesota, Minneapolis, MN; Steven E. Kempers, MD, Minnesota Clinical Study Center, Fridley, MN; Brett King, MD, PhD, Church Street Research Unit, New Haven, CT; Amy J. McMichael, MD, Wake Forest University Health Sciences, Winston Salem, NC; Joseph Merola, MD, MMSc, Brigham and Women's Hospital, Boston, MA; Jeremy E. Moss, MD, PhD, New England Research Associates, LLC, Trumbull, CT; Janet Roberts, MD, Northwest Dermatology and Research Center, LLC, Portland, OR; David Rosmarin, MD, Tufts Medical Center, Boston, MA; Daniel Mitchel Stewart, DO, Michigan Center for Skin Care Research, Clinton Township, MI; Dowling B. Stough, MD, Burke Pharmaceutical Research, Hot Springs, AR; and Antonella Tosti, MD, University of Miami Hospital, Miami, FL. We also thank Dr Rich Leff for his contributions to the planning, facilitation, and analysis of this study. Editorial assistance was provided by Tania Iqbal, PhD, at Complete Healthcare Communications, LLC, an ICON plc company (North Wales, PA), whose work was funded by Incyte Corporation (Wilmington, DE). Publisher Copyright: © 2019 American Academy of Dermatology, Inc.

PY - 2020/2

Y1 - 2020/2

N2 - Background: There are currently no treatments for alopecia areata (AA) that are universally effective or approved by the US Food and Drug Administration. Oral ruxolitinib has shown efficacy in extensive AA. Ruxolitinib cream would potentially avoid systemic adverse effects. Objective: To assess the efficacy and safety of 1.5% ruxolitinib cream in patients with AA who had at least 25% hair loss by Severity of Alopecia Tool score. Methods: This was a 2-part study. Part A was an open-label, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 99% hair loss followed by a 24-week extension period. Part B was a double-blind, vehicle-controlled, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 100% hair loss, followed by a crossover to ruxolitinib cream in the vehicle group for 24 weeks and additional treatment time for the ruxolitinib cream group. Results: Although Part A results suggested potential efficacy of 1.5% ruxolitinib cream, there was no significant difference in hair regrowth based on 50% improvement in Severity of Alopecia Tool scores between patients receiving 1.5% ruxolitinib cream and vehicle in part B. There were no significant safety issues with 1.5% ruxolitinib cream. Limitations: Single strength of ruxolitinib cream. Conclusions: The 1.5% ruxolitinib cream did not have a significant effect in patients with AA.

AB - Background: There are currently no treatments for alopecia areata (AA) that are universally effective or approved by the US Food and Drug Administration. Oral ruxolitinib has shown efficacy in extensive AA. Ruxolitinib cream would potentially avoid systemic adverse effects. Objective: To assess the efficacy and safety of 1.5% ruxolitinib cream in patients with AA who had at least 25% hair loss by Severity of Alopecia Tool score. Methods: This was a 2-part study. Part A was an open-label, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 99% hair loss followed by a 24-week extension period. Part B was a double-blind, vehicle-controlled, 24-week study of 1.5% ruxolitinib cream in patients with 25% to 100% hair loss, followed by a crossover to ruxolitinib cream in the vehicle group for 24 weeks and additional treatment time for the ruxolitinib cream group. Results: Although Part A results suggested potential efficacy of 1.5% ruxolitinib cream, there was no significant difference in hair regrowth based on 50% improvement in Severity of Alopecia Tool scores between patients receiving 1.5% ruxolitinib cream and vehicle in part B. There were no significant safety issues with 1.5% ruxolitinib cream. Limitations: Single strength of ruxolitinib cream. Conclusions: The 1.5% ruxolitinib cream did not have a significant effect in patients with AA.

KW - alopecia areata

KW - clinical trial

KW - ruxolitinib cream

UR - https://www.scopus.com/pages/publications/85076529250

UR - https://www.scopus.com/pages/publications/85076529250#tab=citedBy

U2 - 10.1016/j.jaad.2019.10.016

DO - 10.1016/j.jaad.2019.10.016

M3 - Article

C2 - 31622643

AN - SCOPUS:85076529250

SN - 0190-9622

VL - 82

SP - 412

EP - 419

JO - Journal of the American Academy of Dermatology

JF - Journal of the American Academy of Dermatology

IS - 2

ER -

Ruxolitinib cream for the treatment of patients with alopecia areata: A 2-part, double-blind, randomized, vehicle-controlled phase 2 study

Abstract

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Keywords

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