Investigation of selective JAK1 inhibitor GSK2586184 for the treatment of psoriasis in a randomized placebo-controlled phase IIa study
Summary 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)....
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| Published in: | British journal of dermatology (1951) Vol. 174; no. 5; pp. 985 - 995 |
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| Main Authors: | , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
England
Blackwell Publishing Ltd
01-05-2016
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| Subjects: | |
| Online Access: | Get full text |
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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.
What's already known about this topic?
Inhibition of Janus kinase (JAK) signalling is emerging as an important therapeutic target in the treatment of psoriasis.
What does this study add?
This study shows that GSK2586184 is efficacious in the treatment of plaque psoriasis over a 12‐week period.
Our results suggest that JAK1 selective inhibition may be an effective treatment option for patients with plaque‐type psoriasis, without the laboratory changes seen with broader JAK inhibition.
Our study details the gene expression profile changes observed in uninvolved and involved skin at baseline and in involved skin after 2 weeks of treatment with GSK2586184.
Plain language summary available online |
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| Bibliography: | GlaxoSmithKline ark:/67375/WNG-VWSW19WS-V ArticleID:BJD14399 istex:586DD565865828FE52C9195B07A6C58F70CD501B available online ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 ObjectType-News-3 content type line 23 |
| ISSN: | 0007-0963 1365-2133 |
| DOI: | 10.1111/bjd.14399 |