FDA Approves Stelara for Crohn’s Colitis
This is huge, being the first non-TNF inhibitor approved for Crohn’s Disease. It parallels anti-IL17A Secukinumab being approved for Axial Spondyloarthritis. IL17A antagonism, however, appears to aggravate Crohn’s Disease. IL17 plays a pivotal role in mucosal immunity, and inhibiting it appears to cause candidiasis and worsen IBD.
It therefore comes as a pleasant surprise that Ustekinumab, inhibiting IL12 & 23, should prove to be beneficial for treating Crohn’s Disease. IL23 is upstream to IL17 and 22. So what are we missing here?:
1) Is inhibiting IL12, a Th1 cytokine, really doing the trick for Crohn’s, or perhaps in combination with Th17 inhibition?
2) Is inhibiting a more upstream cytokine IL23 the key to success, meaning inhibiting downstream IL17A alone is inadequate? But wouldn’t inhibiting downstream IL22 as well compromise mucosal repair, or does IL22/Th22 play a pathological role in Crohn’s we’re not yet aware of?