IBD biologic sequencing patterns reveal the early-line ustekinumab opportunity

Reading the signal

The IBD (inflammatory bowel disease) biologic class has historically been anti-TNF-first by convention, with anti-TNF agents (infliximab, adalimumab, certolizumab pegol, golimumab in ulcerative colitis) as the default first-line biologic across Crohn's disease and ulcerative colitis. The newer mechanisms (anti-integrin vedolizumab, IL-12/23 ustekinumab, IL-23 risankizumab and others, JAK and S1P modulators in UC) have positioned in second-line and beyond.

Real-world data accumulating over the past three years shows the convention shifting:

• Ustekinumab in Crohn's disease has moved earlier in the line of therapy in real-world prescribing patterns, supported by durability data and by safety profile in patients with comorbidities that complicate anti-TNF use
• Risankizumab and the IL-23-only subclass are following the same trajectory in Crohn's disease and increasingly in ulcerative colitis
• The S1P modulator ozanimod and JAK inhibitor tofacitinib have specific positioning in ulcerative colitis with the safety frame shaping line placement
• Vedolizumab continues to position on its safety profile, particularly in older or more comorbid patients

The cumulative effect is that the anti-TNF first-line default is not the universal default it was, and the early-line opportunity for non-TNF biologics is structurally larger than it was three years ago.

Commercial implications

For sponsors of IBD biologics across mechanisms:

1. The early-line versus late-line commercial logic is reshaping for non-TNF mechanisms. Assets with strong durability data and favourable safety profiles are positioned to compete in first-line in a way they were not historically
2. The step-therapy protocol layer is the operational determinant. Markets with step-therapy protocols that mandate anti-TNF first lag the prescriber-pattern shift; markets with more open protocols see the shift faster
3. The anti-TNF class continues to have a substantial real-world presence but its first-line market share is structurally smaller than the historical convention assumed

What we are watching

• Step-therapy protocol evolution and the rate at which IBD biologic access expands beyond anti-TNF first-line
• Real-world durability data accumulating on the IL-12/23 and IL-23 mechanisms in IBD, particularly at the 5+ year horizon
• Late-stage IBD biologic and small-molecule pipeline (next-generation IL-23 mechanisms, next-generation S1P modulators, novel mechanisms entering pivotal trials) and how they position into the reshaping access landscape