Does IL-21 suppression reduce Crohn's symptoms?

"Cytokine Regulation of Gut Inflammation in IBD" in Int J Clin Rev (2010)
"Anti-cytokine therapies, such as the three licensed anti-tumor necrosis factor-a (anti-TNF-a) antibodies, have transformed the management of difficult-to-treat IBD patients. However, only 40–50% of patients respond to these agents, there are side effects, and efficacy wanes with time. Consequently, great interest remains in new agents that may be more effective than anti-TNF-a antibodies. Here, we argue that no single agent will ever be clinically better than anti-TNF-a antibodies, and that there is no “Holy Grail” anti-cytokine biological therapy that will be clinically effective in all patients. Instead, work in this area should be focused on identifying new drugs targeting other cytokines (here, we concentrate on the interleukin-17 [IL-17] family and IL-21), which can be used logically in individual patients based on biomarker studies, as well as after failure of a first, second, or third biological treatment." [emphasis mine]

Will suppression of IL 17 cytokines reduce the symptoms of CD in anti-TNF-resistant patients?

"Cytokine Regulation of Gut Inflammation in IBD" in Int J Clin Rev (2010)
"Anti-cytokine therapies, such as the three licensed anti-tumor necrosis factor-a (anti-TNF-a) antibodies, have transformed the management of difficult-to-treat IBD patients. However, only 40–50% of patients respond to these agents, there are side effects, and efficacy wanes with time. Consequently, great interest remains in new agents that may be more effective than anti-TNF-a antibodies. Here, we argue that no single agent will ever be clinically better than anti-TNF-a antibodies, and that there is no “Holy Grail” anti-cytokine biological therapy that will be clinically effective in all patients. Instead, work in this area should be focused on identifying new drugs targeting other cytokines (here, we concentrate on the interleukin-17 [IL-17] family and IL-21), which can be used logically in individual patients based on biomarker studies, as well as after failure of a first, second, or third biological treatment." [emphasis mine]

Who are Humira nonresponders?

"Loss of Response and Need for Adalimumab Dose Intensification in Crohn's Disease: A Systematic Review" in J Am Gastroenterol (2011)
"Predictors for loss of response or dose escalation were male gender, current/former smoker status, family history of inflammatory bowel disease, isolated colonic disease, extra-intestinal manifestations, 80/40 mg induction therapy, longer disease duration, greater baseline Crohn's Disease Activity Index, concomitant corticosteroid use, no deep remission at week 12, low serum trough concentrations of adalimumab, previous infliximab non-response and being previously treated with an anti-tumor necrosis factor agent. Overall, around one fifth of adult patients require dose intensification and experience a loss of response after initiation of adalimumab therapy. Adalimumab dose escalation permits response to be regained in the majority of patients."