Positioning and sequencing of advanced therapies in inflammatory bowel disease: A guide for clinical practice

Table 4 Practical pearls in positioning and sequencing advanced therapies in Crohn's disease and the available evidence base

Practical pearls in positioning and sequencing advanced therapies in Crohn's disease and the available evidence base
For first line use in active mild-to-moderate CD refractory to conventional therapy, anti-TNF therapy, vedolizumab, anti-IL 12/23, anti-IL-23p19 may be similarly effective (RWE, NMA)
Vedolizumab is more effective when used in the first line (RCT, RWE)
In the scenario where pharmacoeconomic issues are a priority, initial therapy with biosimilars of infliximab, adalimumab or ustekinumab makes the first-line choice more cost-effective
Anti-TNF therapy (infliximab or adalimumab) preferably combined with thiopurines (for infliximab) may be the first line of treatment in severe CD (stricturing or penetrating phenotype, extensive small bowel disease, complex perianal disease, high inflammatory load or severe extraintestinal manifestation) (RCT, RWE, NMA)
Anti-TNF and anti-IL12/23 therapy are similarly effective in bio-naive patients with uncomplicated, early-onset moderate to severe CD (RCT, RWE)
Vedolizumab, anti-IL12/23, and Anti-IL-23p19 may be considered as first-line choice when safety issues become outstanding (RWE, NMA)
After failure of the first anti-TNF, advanced second-line therapies are less effective, including a second anti-TNF (RCT, RWE)
Anti-IL 12/23, anti-IL-23p19 and upadacitinib agents are still effective after failure of one or more anti-TNF (RCT, RWE)
Anti-TNF, upadacitinib, and IL-12/23 or IL-23p19 inhibitors are also effective after vedolizumab failure (RWE)
Anti-TNF, upadacitinib, and IL-23p19 inhibitors are effective after anti-interleukin 12/23 failure (RWE)
Anti-IL-23p19 are more effective than IL-12/23 inhibitors after failure of one or more anti-TNFs (RCT), with unclear data regarding upadacitinib positioning in this setting; A second anti-TNF associated with an immunosuppressor could be considered as a second choice, after pharmacokinetic failure due to immunogenicity of the first anti-TNF (RWE). The use of upadacitinib may be particularly favored for patients with high clearance of biologics, hypoalbuminemia, colonic CD, concomitant axial spondyloarthritis, or perianal fistulizing disease refractory to anti-TNF therapy

Janus kinase inhibitors (including upadacitinib) are not considered in biologic-naive patients in some countries, given United States Food and Drug Administration labeling restricting the use of this class of drugs to biologic/tumoral necrosis factor antagonist exposed individuals. CD: Crohn's disease; IL: Interleukin; TNF: Tumoral necrosis factor; NMA: Network meta-analysis; RWE: Real-world evidence; RCT: Randomized controlled trial.