Anti-IL-23 Therapy for Crohn's Disease: What a 2026 Cochrane Review Found About Inducing Remission

For people with moderately to severely active Crohn's disease, deciding whether to start a biologic medicine (and which one) is one of the more significant conversations they have with their clinical team. The evidence base for these decisions has grown substantially over the past decade, and it continues to be updated as new systematic reviews pool and re-examine the available trial data.

One important drug class in this landscape is anti-IL-12/23p40 antibodies. A 2026 Cochrane systematic review set out to synthesise the current evidence on how effective these medicines are at inducing remission in active Crohn's disease.

What Are Anti-IL-12/23p40 Antibodies?

Crohn's disease involves a dysregulated immune response that drives chronic inflammation in the digestive tract. Two cytokines, interleukin-12 (IL-12) and interleukin-23 (IL-23), play a central role in sustaining this inflammatory response. Both share a structural component called the p40 subunit, which is the target of anti-IL-12/23p40 antibodies.

By binding to the p40 subunit, these medicines block both IL-12 and IL-23 signalling simultaneously, interrupting the inflammatory cascade. The principal approved medicine in this class for Crohn's disease is ustekinumab (brand name Stelara), a fully human monoclonal antibody administered by intravenous infusion for the initial dose and then by subcutaneous injection for maintenance.

The NHS describes biological medicines for Crohn's disease, including ustekinumab, as medicines that target specific proteins involved in inflammation, and notes they are typically considered for people with moderate to severe Crohn's disease who have not responded to other treatments (NHS: Crohn's disease treatment).

What the 2026 Cochrane Review Examined

Cochrane systematic reviews are designed to provide the highest level of synthesised evidence. They apply prespecified, rigorous methodology to identify all relevant randomised controlled trials on a clinical question, assess the quality and risk of bias across those trials, and pool the results to produce evidence-graded conclusions.

The 2026 Cochrane review on anti-IL-12/23p40 antibodies for Crohn's disease focused specifically on the induction phase: the initial period of treatment during which the aim is to bring active disease under control as quickly as possible, producing a measurable clinical response or remission (Anti-IL-12/23p40 antibodies for induction of remission in Crohn's disease, Cochrane Database of Systematic Reviews, 2026). The review searched for randomised controlled trials comparing these antibodies against placebo or active comparators in adults with active Crohn's disease.

What the Review Found

The systematic review found that anti-IL-12/23p40 antibodies were more effective than placebo at inducing both clinical response and clinical remission in patients with moderately to severely active Crohn's disease (pubmed:40357993). This conclusion is consistent with the regulatory approvals that ustekinumab has received across major jurisdictions for this indication.

The review also examined safety data from the included trials. Anti-IL-12/23p40 antibodies were generally well tolerated during the induction phase, with rates of serious adverse events broadly comparable to placebo in the pooled data (pubmed:40357993). As with all immunomodulatory medicines, the potential for infection and other adverse effects over the long term remains an ongoing consideration, which is why monitoring and regular review by a clinical team are part of standard care.

Understanding What Induction Evidence Means

It is worth being clear about what this evidence does and does not show. The Cochrane review focused on the induction phase, typically the first six to eight weeks after starting treatment. Induction remission does not mean permanent resolution of Crohn's disease. Most patients who achieve remission during induction require ongoing maintenance therapy to sustain it, and the evidence on maintenance treatment is addressed in separate Cochrane reviews and clinical guidelines.

This distinction matters for patients who want to set realistic expectations about what starting a biologic can and cannot achieve. Induction is the beginning of a longer treatment journey, not the end.

Who This Evidence Is Most Relevant To

Anti-IL-12/23p40 therapy with ustekinumab is used in adults with moderately to severely active Crohn's disease. It is considered for patients who have not responded adequately to conventional therapy such as corticosteroids or immunomodulators, and for those who have failed, lost response to, or are unable to tolerate TNF inhibitors such as infliximab or adalimumab. It is also used in some patients as a first-line biologic where clinical factors make it the preferred option.

For patients already taking ustekinumab, this Cochrane synthesis provides context for understanding why it was chosen and what the evidence says about its effectiveness at the induction stage. For those who have not yet started biologic therapy but are being assessed for it, the review confirms that the evidence base for this drug class now rests on a sufficiently broad body of randomised trial data to support formal Cochrane synthesis, an important milestone in the trajectory of any treatment's evidence base.

A Note on Individual Responses

Population-level evidence from a systematic review describes averages across large groups of trial participants. Not every person with Crohn's disease who takes an anti-IL-12/23p40 antibody will achieve remission during induction; some will respond and others will not. The decision about which biologic to use, when to use it, and what to do if induction fails is made by clinical teams in partnership with individual patients, taking into account disease location and severity, previous treatment history, comorbidities, and patient preferences.

If you have Crohn's disease and are considering biologic therapy, or if you are already taking ustekinumab and want to understand what the evidence says about how it works, speak with your specialist or IBD nurse. They can explain whether anti-IL-12/23 therapy is appropriate for your disease stage, treatment history, and personal circumstances. Treatment decisions for moderate-to-severe Crohn's disease are complex and should always be made in partnership with your care team.