TNF and inflammatory bowel disease: A recent systematic review and meta-analysis found that the prevalent indication for DTT (two biologics or one biologic + JAK inhibitor) in IBD patients is refractory disease (81%), whereas extraintestinal manifestations account for 12% of all indications [94]; among all possible combinations, anti-integrin (vedolizumab or natalizumab) was the biologic most frequently associated with other drugs (anti-TNFα, anti-IL12/23, or JAK inhibitors), probably due to its gut selectivity and safety profile.