Abstract:
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-4', 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.
journal_name
Expert Opin Investig Drugsjournal_title
Expert opinion on investigational drugsauthors
Wiese MD,Manning-Bennett AT,Abuhelwa AYdoi
10.1080/13543784.2020.1752660subject
Has Abstractpub_date
2020-05-01 00:00:00pages
475-482issue
5eissn
1354-3784issn
1744-7658journal_volume
29pub_type
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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journal_title:Expert opinion on investigational drugs
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