The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis
Secukinumab's 2012 proof of concept trial in Crohn's Disease was also called off prematurely when a third of patients withdrew, mainly out of lack of efficacy, but the disease also worsened in 5 patients, 4 of whom from the active arm. Suspicion feel on the 2 high intravenous doses given 3 weeks apart.
Now, Brodalumab (inhibiting both IL17a & IL17F through blocking IL17RA -- the receptor) rushed in where other IL17 inhibitors feared to tread; and it's history.
Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn's disease: unexpected results of a randomised, double-blind placebo-controlled trial
In my earlier posts on the efficacy of Ustekinumab (anti-IL12/23 -Oct 18) and Risankizumab (anti-IL23 -- Aug 14) in the treatment of Crohn's Disease, I speculated on why an upstream IL23 inhibition should work when a downstream IL17A inhibition should fail and even worsen disease. Was IL17A blockade too strong, too weak, or is Crohn's mainly a Th1 rather than Th17 disease?
Well, based on this and other similar studies, I'm much convinced that it's "too strong". The housekeeping role of the Th17 cytokines (including IL17A, IL17F, IL22) is critical for mucosal surveillance and integrity. IL23 blockade targets the excessive pathogenic activation of the Th17 pathway, sparing the necessary background IL17A/F production from other non-Th17 cells.