Inflammatory Bowel Disease

The Prevalence and Incidence of Axial and Peripheral Spondyloarthritis in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis

J Crohns Colitis. 2016 Nov 4. pii: jjw199. [Epub ahead of print] Review
ncbi.nlm.nih.gov|By Karreman MC , et al.

The American Journal of Gastroenterology is published by Nature Publishing Group (NPG) on behalf of the American College of Gastroenterology (ACG). Ranked the #1 clinical journal covering gastroenterology and hepatology*, The American Journal of Gastroenterology (AJG) provides practical and professi...
nature.com

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

Contributors Charles Barish, Wake Research Associates, Raleigh NC, United States; Richard Bernstein, University of Manitoba, Winnipeg, Manitoba, Canada; Robert Burakoff, Brigham and Women's Hospital, Division of Gastroenterology, Boston MA United States; Brian Feagan, Robarts Research Institute Univ...
gut.bmj.com

Large image of Figure 1.
Interleukin (IL-23) is considered a critical regulator of IL-17 in lymphocytes. Whereas antibodies targeting IL-23 ameliorate colitis, IL-17 neutralization exacerbates disease. Cua and colleagues and Maxwell and colleagues show that IL-17…
cell.com

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.

IL-23 inhibitor risankizumab induces remission in Phase II study in patients with moderate-to-severe Crohn’s disease

IL-23 inhibitor risankizumab induces remission in Phase II study in patients with moderate-to-severe Crohn’s disease
boehringer-ingelheim.com

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