PMID- 36972293
OWN - NLM
STAT- MEDLINE
DCOM- 20230710
LR  - 20231120
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 189
IP  - 1
DP  - 2023 Jul 7
TI  - Efficacy and safety of topical brepocitinib cream for mild-to-moderate chronic 
      plaque psoriasis: a phase IIb randomized double-blind vehicle-controlled 
      parallel-group study.
PG  - 33-41
LID - 10.1093/bjd/ljad098 [doi]
AB  - BACKGROUND: Plaque psoriasis (PsO) is an inflammatory skin disease driven, in 
      part, by the activation of Janus kinase (JAK) signalling pathways. OBJECTIVES: To 
      assess the efficacy and safety of multiple doses of topical brepocitinib, a 
      tyrosine kinase 2/JAK1 inhibitor, in participants with mild-to-moderate PsO. 
      METHODS: This phase IIb multicentre randomized double-blind study was conducted 
      in two stages. In stage 1, participants received one of eight treatments for 12 
      weeks: brepocitinib 0.1% once daily, 0.3% once or twice daily, 1.0% once or twice 
      daily, 3.0% once daily, or vehicle once or twice daily. In stage 2, participants 
      received brepocitinib 3.0% twice daily or vehicle twice daily. The primary 
      endpoint was the change from baseline in Psoriasis Area and Severity Index (PASI) 
      score at week 12, analysed using analysis of covariance. The key secondary 
      endpoint was the proportion of participants who achieved a Physician Global 
      Assessment response [score of clear (0) or almost clear (1) and an improvement of 
      >/= 2 points from baseline] at week 12. Additional secondary endpoints included the 
      difference vs. vehicle in change from baseline in PASI, using mixed-model 
      repeated measures, and the change from baseline in Peak Pruritus Numerical Rating 
      Scale at week 12. Safety was monitored. RESULTS: Overall, 344 participants were 
      randomized. Topical brepocitinib did not result in statistically significant 
      changes compared with respective vehicle controls in the primary or key secondary 
      efficacy endpoints for any dose group. At week 12, least squares mean change from 
      baseline in PASI score ranged from -1.4 to -2.4 for the brepocitinib once-daily 
      groups vs. -1.6 for vehicle once daily, and from -2.5 to -3.0 for the 
      brepocitinib twice-daily groups vs. -2.2 for vehicle twice daily. From week 8, 
      change from baseline in PASI score separated from vehicle in all brepocitinib 
      twice daily groups. Brepocitinib was well tolerated, with adverse events (AEs) 
      occurring at similar rates across groups. One participant in the brepocitinib 
      1.0% once-daily group developed a treatment-related AE of herpes zoster in the 
      neck area. CONCLUSIONS: Topical brepocitinib was well tolerated but did not 
      result in statistically significant changes compared with vehicle when 
      administered at the doses evaluated to treat signs and symptoms of 
      mild-to-moderate PsO.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of British 
      Association of Dermatologists. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Landis, Megan N
AU  - Landis MN
AD  - Department of Medicine (Dermatology), University of Louisville School of 
      Medicine, Louisville, KY, USA.
AD  - Dermatology and Skin Cancer Center of South Indiana, Corydon, IN, USA.
FAU - Smith, Stacy R
AU  - Smith SR
AD  - California Dermatology and Clinical Research Institute, Encinitas, CA, USA.
FAU - Berstein, Gabriel
AU  - Berstein G
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Fetterly, Gerald
AU  - Fetterly G
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Ghosh, Pranab
AU  - Ghosh P
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Feng, Gang
AU  - Feng G
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Pradhan, Vivek
AU  - Pradhan V
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Aggarwal, Sudeepta
AU  - Aggarwal S
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Banfield, Christopher
AU  - Banfield C
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Peeva, Elena
AU  - Peeva E
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Vincent, Michael S
AU  - Vincent MS
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Beebe, Jean S
AU  - Beebe JS
AD  - Pfizer Inc., Cambridge, MA, USA.
FAU - Tarabar, Sanela
AU  - Tarabar S
AD  - Pfizer Inc., Cambridge, MA, USA.
LA  - eng
GR  - Pfizer Inc/
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Janus Kinase Inhibitors)
RN  - 0 (Emollients)
SB  - IM
CIN - Br J Dermatol. 2023 May 08;:. PMID: 37151092
EIN - Br J Dermatol. 2023 Oct 25;189(5):e81. PMID: 37740959
MH  - Humans
MH  - Double-Blind Method
MH  - *Psoriasis/drug therapy
MH  - *Janus Kinase Inhibitors
MH  - Emollients/therapeutic use
MH  - Pruritus
MH  - Treatment Outcome
MH  - Severity of Illness Index
COIS- Conflicts of interest M.N.L. has served as investigator for AbbVie, Amgen, 
      Galderma, Incyte, Novartis and Pfizer, and has served on an advisory board for 
      Galderma. S.R.S. has been a consultant and member of the speaker's bureau for 
      AbbVie, Janssen and Lilly, and has been a clinical investigator for AbbVie, 
      Aclaris, Arcutis, Galderma, Leo Pharmaceuticals, Lilly, Pfizer and Regeneron. 
      G.B., G.F., P.G., G.F., V.P., S.A., C.B., E.P., M.S.V. and S.T. are employees of 
      and shareholders in Pfizer Inc. J.S.B. was an employee of and shareholder in 
      Pfizer Inc. at the time at which this study was conducted.
EDAT- 2023/03/28 06:00
MHDA- 2023/07/10 06:42
CRDT- 2023/03/27 13:43
PHST- 2022/10/20 00:00 [received]
PHST- 2023/03/16 00:00 [revised]
PHST- 2023/03/18 00:00 [accepted]
PHST- 2023/07/10 06:42 [medline]
PHST- 2023/03/28 06:00 [pubmed]
PHST- 2023/03/27 13:43 [entrez]
AID - 7087205 [pii]
AID - 10.1093/bjd/ljad098 [doi]
PST - ppublish
SO  - Br J Dermatol. 2023 Jul 7;189(1):33-41. doi: 10.1093/bjd/ljad098.