Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study. Academic Article uri icon

Overview

abstract

  • Receptor-interacting protein kinase 1 (RIPK1), a regulator of inflammation and cell death, is a potential therapeutic target in immune-mediated inflammatory diseases (IMIDs). The objective of this phase IIa multicenter, randomized, double-blind, placebo-controlled study was to evaluate safety, tolerability pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in plaque-type psoriasis. Psoriasis patients (N = 65) were randomized to 60 mg twice daily (b.i.d.) or three times daily (t.i.d.), or placebo for 84 days. Most adverse events (AEs) were mild with no severe drug-related AEs reported. Plaque Lesion Severity Sum improved with b.i.d. treatment compared with placebo; interpretation of t.i.d. treatment results was complicated by a high placebo response. Reductions in epidermal thickness and infiltration by CD3+ T cells in the epidermis and dermis were observed compared with placebo. Results support the rationale for additional studies on RIPK1 inhibition in IMIDs.

publication date

  • July 7, 2020

Research

keywords

  • Dermis
  • Oxazepines
  • Protein Kinase Inhibitors
  • Psoriasis
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Triazoles

Identity

PubMed Central ID

  • PMC7540322

Scopus Document Identifier

  • 85086937938

Digital Object Identifier (DOI)

  • 10.1002/cpt.1852

PubMed ID

  • 32301501

Additional Document Info

volume

  • 108

issue

  • 4