Although modest activity was shown in RA in a randomized phase 2 trial with an IRAK4 kinase inhibitor, PF-06650833 (ref. 25), that same drug did not show activity compared to placebo in a phase 2 trial in HS26, suggesting that efficacy may be limited when IRAK4 targeting does not address the kinase and scaffolding functions of the protein. Here, IRAK4 is linked to rheumatoid arthritis.