Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis

Michael D. Wiese, Arkady T. Manning-Bennett, Ahmad Y. Abuhelwa

Research output: Contribution to journalReview articlepeer-review

12 Citations (Scopus)


Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that can lead to permanent disability and deformity. Despite current treatment modalities, many patients are still unable to reach remission. Interleukin-1 receptor-associated kinase 4 (IRAK-4) inhibitors are novel agents designed to suppress immune signaling pathways involved in inflammation and joint destruction in RA. Four IRAK-4 inhibitors have entered clinical trials. Areas covered: This review summarizes the current stage of development of IRAK-4 inhibitors in clinical trials, detailing their chemistry, pharmacokinetics, and therapeutic potential in the treatment of RA. PubMed, Embase and restricted Google searches were conducted using the term ‘IRAK-4ʹ, and publicly accessible clinical trial databases were reviewed. Expert opinion: IRAK-4 inhibitors are an exciting therapeutic option in RA management because unlike other targeted disease-modifying agents, they target the innate immune system. The role of IRAK-4 as a key component of Toll/Interleukin-1 receptor signaling and its potential for a low rate of infectious complications is particularly exciting and this may facilitate their use in combination treatment. A key aspect of upcoming clinical trials will be the identification of biomarkers predictive of treatment efficacy, which will help to define if and how they will be used in the clinic.

Original languageEnglish
Pages (from-to)475-482
Number of pages8
JournalExpert Opinion On Investigational Drugs
Issue number5
Early online date17 Apr 2020
Publication statusPublished - 3 May 2020
Externally publishedYes


  • BAY1834845
  • CA-4948
  • interleukin-1 receptor associated kinase 4
  • IRAK-4
  • PF-06650833
  • Rheumatoid arthritis
  • toll-like receptors


Dive into the research topics of 'Investigational IRAK-4 inhibitors for the treatment of rheumatoid arthritis'. Together they form a unique fingerprint.

Cite this