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

Table 3 Practical pearls in positioning and sequencing advanced therapies in ulcerative colitis and the available evidence base

Practical pearls in positioning and sequencing advanced therapies in ulcerative colitis and the available evidence base
For first line use in moderate-to-severe UC, vedolizumab demonstrated significantly higher rates of clinical remission and mucosal healing at week 52 when compared to adalimumab (RCT)
Upadacitinib is the most effective therapy for moderately-to-severely active UC, in both biologic-naive and biologic-exposed populations (NMA)
In the clinical setting in which upadacitinib cannot be used as first-line therapy (due to label restrictions or contraindications), infliximab and vedolizumab are probably the most adequate therapies to be used in the induction of remission in biologic-naive patients with moderate to severe UC (NMA, RWE)
Infliximab, ozanimod, risankizumab, and guselkumab provide a greater clinical benefit in achieving induction remission compared to adalimumab and mirikizumab in biologic-naive patients with moderate-to-severe UC, when JAK inhibitors are excluded as a first-line treatment option (NMA)
Upadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Selective IL-23 inhibitors, such as risankizumab and guselkumab, also exhibited high efficacy in achieving these outcomes (NMA)
In the clinical setting of moderate to severe steroid-responsive or corticosteroid-dependent UC, where the patient is not at imminent risk of hospitalization, and considering the balance of effectiveness and safety, vedolizumab can be considered as first-line therapy, although ustekinumab and interleukin-23p19 inhibitors are also good options (RWE)
In patient's refractory to first-line therapy with vedolizumab, the use of infliximab, ustekinumab, IL-23p19 inhibitors or JAK inhibitors are effective in inducing remission (RWE)
Tofacitinib and ustekinumab showed comparable corticosteroid-free remission, early response rates, and mucosal healing in UC patients refractory to anti-TNF therapy (RWE)
Tofacitinib demonstrated significantly higher corticosteroid-free clinical remission, biochemical remission and fecal calprotectin ≤ 250 μg/g when compared to vedolizumab in anti-TNF experienced patients (RWE)
Vedolizumab was superior to infliximab in patients with moderate-to-severe UC who had failed a first subcutaneous anti-TNF (adalimumab or golimumab), in clinical and endoscopic outcomes (RCT)
Lymphocyte trafficking inhibitors (anti-integrins and S1P receptor modulators) demonstrated greater efficacy in TNF antagonist-naive compared to TNF antagonist-exposed patients (NMA)
S1P receptor modulators, such as ozanimod and etrasimod, are oral agents that may be considered as first-line therapy in patients with mild to moderate UC refractory to aminosalicylates (RCT, RWE)
Ustekinumab, mirikizumab, risankizumab guselkumab and etrasimod demonstrated efficacy in moderate-to-severe UC failed prior biologic therapy (RCT)
JAK inhibitors represent promising therapeutic options for ASUC, particularly in those with prior infliximab failure (systematic review)
Combining hydrocortisone with tofacitinib in ASUC increases the likelihood of treatment response and reduces the need for salvage therapies such as colectomy (RCT)
Upadacitinib demonstrated efficacy and safety comparable to infliximab in patients with ASUC, with no significant differences in colectomy rates (RWE)
In patients with moderate to severe UC without imminent risk of hospitalization, who are elderly, frail, have severe comorbidities, or are at high risk of major cardiovascular events or thromboembolic events, vedolizumab, ustekinumab, or IL-23p19 inhibitors are the preferred therapies, and JAK inhibitors should be avoided in these clinical contexts (NMA, RWE)
In the scenario where pharmacoeconomic issues are a priority, initial therapy with biosimilars makes the first-line choice more cost-effective

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. ASUC: Acute severe ulcerative colitis; RCT: Randomized controlled trial; UC: Ulcerative colitis; NMA: Network meta-analysis; RWE: Real-world evidence; JAK: Janus kinase; IL: Interleukin; TNF: Tumoral necrosis factor; S1P: Sphingosine 1-phosphate.