Ustekinumab for Crohn's

FDA Approves Stelara for Crohn’s Colitis

The anti-IL-12/IL-23 inhibitor, Stelara…

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?

Nor-Switch Study Shows it’s Safe to Switch to a Biosimilar

The results of the Nor-Switch study were presented at the United European Gastroenterology annual congress this week demonstrating no significant difference in effect, adverse effects or antibody formation in patients switched from Remicade to the biosimilar infliximab (CT-P13, Remsima). Outcomes we…