PMID- 26785220
OWN - NLM
STAT- MEDLINE
DCOM- 20170313
LR  - 20170817
IS  - 1365-2133 (Electronic)
IS  - 0007-0963 (Linking)
VI  - 174
IP  - 5
DP  - 2016 May
TI  - Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of 
      psoriasis in a randomized placebo-controlled phase IIa study.
PG  - 985-95
LID - 10.1111/bjd.14399 [doi]
AB  - BACKGROUND: GSK2586184 is a selective oral Janus kinase (JAK)1 inhibitor being 
      evaluated as a treatment for moderate-to-severe plaque-type psoriasis. 
      OBJECTIVES: To assess the relationship between dose of GSK2586184 and clinical 
      response, primarily by the Psoriasis Area Severity Index (PASI). METHODS: Sixty 
      patients with moderate-to-severe plaque psoriasis were randomized to cohort A: 
      100 mg, 200 mg or 400 mg GSK2586184 twice daily or placebo; and eight were 
      randomized to open-label cohort B, a small exploratory cohort treated with 400 mg 
      GSK2586184 twice daily, to explore differential gene expression. RESULTS: At week 
      12, a 75% reduction in PASI (PASI 75) response rates in the intent-to-treat 
      population were 0% in the placebo group compared with 13%, 25% and 57% in the 100 
      mg, 200 mg and 400 mg GSK2586184 twice-daily groups, respectively. Increases in 
      the proportion of PASI 75 responses were seen across all dose levels by week 4. 
      Improvement in itch and quality of life were observed at all doses relative to 
      placebo with the greatest improvement seen in the 400-mg dose group. Overall, the 
      incidence of adverse events (AEs) was similar across treatment groups, and no 
      relationship between frequency of AE and GSK2586184 dose was identified. 
      Differential gene expression was observed in involved and uninvolved skin at 
      baseline and in involved skin after 2 weeks of treatment with GSK2586184. 
      CONCLUSIONS: Our study demonstrates that 12 weeks of treatment with GSK2586184 
      resulted in clinical improvement and was generally well tolerated in patients 
      with moderate-to-severe plaque-type psoriasis.
CI  - (c) 2016 British Association of Dermatologists.
FAU - Ludbrook, V J
AU  - Ludbrook VJ
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Hicks, K J
AU  - Hicks KJ
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Hanrott, K E
AU  - Hanrott KE
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Patel, J S
AU  - Patel JS
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Binks, M H
AU  - Binks MH
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Wyres, M R
AU  - Wyres MR
AD  - Stiefel, Research Triangle Park, NC, U.S.A.
FAU - Watson, J
AU  - Watson J
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Wilson, P
AU  - Wilson P
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Simeoni, M
AU  - Simeoni M
AD  - GlaxoSmithKline, Gunnels Wood Road, Stevenage, SG4 7AE, U.K.
FAU - Schifano, L A
AU  - Schifano LA
AD  - GlaxoSmithKline, Research Triangle Park, NC, U.S.A.
FAU - Reich, K
AU  - Reich K
AD  - Dermatologikum Hamburg and SCIderm Research Center, Hamburg, Germany.
FAU - Griffiths, C E M
AU  - Griffiths CE
AD  - Dermatology Centre, Salford Royal Hospital, The University of Manchester, 
      Manchester Academic Health Science Centre, Manchester, M6 8HD, U.K.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20160407
PL  - England
TA  - Br J Dermatol
JT  - The British journal of dermatology
JID - 0004041
RN  - 0 (Azetidines)
RN  - 0 (Dermatologic Agents)
RN  - 0 (GSK2586184)
RN  - 0 (Triazoles)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Azetidines/*administration & dosage/pharmacokinetics
MH  - Dermatologic Agents/*administration & dosage/pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Janus Kinase 1/antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Psoriasis/*drug therapy/genetics
MH  - Quality of Life
MH  - Treatment Outcome
MH  - Triazoles/*administration & dosage/pharmacokinetics
MH  - Young Adult
EDAT- 2016/01/20 06:00
MHDA- 2017/03/14 06:00
CRDT- 2016/01/20 06:00
PHST- 2016/01/06 00:00 [accepted]
PHST- 2016/01/20 06:00 [entrez]
PHST- 2016/01/20 06:00 [pubmed]
PHST- 2017/03/14 06:00 [medline]
AID - 10.1111/bjd.14399 [doi]
PST - ppublish
SO  - Br J Dermatol. 2016 May;174(5):985-95. doi: 10.1111/bjd.14399. Epub 2016 Apr 7.