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Walker A, Erwig L, Foster K, et al. Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Exp Dermatol. 2020;30(11):1686-1692doi: 10.1111/exd.14253.
Walker, A., Erwig, L., Foster, K., Nevin, K., Wenzel, J., Worm, M., Williams, N., Ratia, N., Hoang, B., Schneider-Merck, T., Gisbert, S., Carnarius, H., & Dickson, M. (2021). Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Experimental dermatology, 30(11), 1686-1692. https://doi.org/10.1111/exd.14253
Walker, Alex, et al. "Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study." Experimental dermatology vol. 30,11 (2021): 1686-1692. doi: https://doi.org/10.1111/exd.14253
Walker A, Erwig L, Foster K, Nevin K, Wenzel J, Worm M, Williams N, Ratia N, Hoang B, Schneider-Merck T, Gisbert S, Carnarius H, Dickson M. Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study. Exp Dermatol. 2021 Nov;30(11):1686-1692. doi: 10.1111/exd.14253. Epub 2020 Dec 17. PMID: 33336508; PMCID: PMC8596667.
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Exp Dermatol. 2021 Nov;30(11):1686-1692. doi: 10.1111/exd.14253. Epub 2020 Dec 17.

Safety, pharmacokinetics and pharmacodynamics of a topical SYK inhibitor in cutaneous lupus erythematosus: A double-blind Phase Ib study.

Experimental dermatology

Alex Walker, Lars Erwig, Katie Foster, Katherine Nevin, Joerg Wenzel, Margitta Worm, Nicola Williams, Nirav Ratia, Bao Hoang, Tanja Schneider-Merck, Sophie Gisbert, Heike Carnarius, Marion Dickson

Affiliations

  1. GSK, Stevenage, UK.
  2. University Hospital of Bonn, Bonn, Germany.
  3. Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité, Berlin, Germany.
  4. GSK, Collegeville, PA, USA.
  5. GSK, Hamburg, Germany.
  6. GSK, Uxbridge, UK.

PMID: 33336508 PMCID: PMC8596667 DOI: 10.1111/exd.14253

Abstract

The immunoregulator spleen tyrosine kinase (SYK) is upregulated in cutaneous lupus erythematosus (CLE). This double-blind, multicentre, Phase Ib study evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical efficacy of the selective SYK inhibitor GSK2646264 in active CLE lesions. Two lesions from each participant (n = 11) were each randomized to topical application of 1% (w/w) GSK2646264 or placebo for 28 days; all participants received GSK2646264 and placebo. The primary endpoint was safety and tolerability of GSK2646264, assessed by adverse event incidence and a skin tolerability test. Secondary endpoints included change from baseline in clinical activity and mRNA expression of interferon-related genes in skin biopsies. Levels of several immune cell markers were evaluated over time. Eight (73%) participants experienced ≥ 1 adverse event (all mild in intensity), and maximal dermal response was similar for GSK2646264 and placebo. The expression of several interferon-related genes, including CXCL10 and OAS1, showed modest decreases from baseline after 28 days of treatment with GSK2646264 compared with placebo. Similar findings were observed for CD3 + T cell and CD11c + dendritic cell levels; however, overall clinical activity remained unchanged with GSK2646264 vs. placebo. Further studies are warranted to assess SYK inhibitors as potential treatment for CLE.

© 2020 Glaxo Group Limited. Experimental Dermatology published by John Wiley & Sons Ltd.

Keywords: SYK Kinase; cutaneous lupus erythematosus; interferons; pharmacology; safety

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