Comparing All Biologics for Crohn's Disease: What a 2026 Cochrane Network Meta-Analysis Found

For people living with Crohn's disease that has not responded to standard treatments, biologic medicines are often the next step. But which biologic? And how do they compare with each other? These questions are hard to answer from individual drug studies alone, because most randomised trials test one drug against placebo rather than directly against competing treatments.

A network meta-analysis attempts to solve this by drawing together all available trial evidence and using statistical methods to rank treatments that have never been directly compared head-to-head. In June 2026, the Cochrane Collaboration published a network meta-analysis pooling data from 94 randomised controlled trials of biologic drugs in Crohn's disease. This article explains what the analysis found and what it means for patients.

What Crohn's Disease Is

Crohn's disease is a chronic inflammatory bowel condition that can affect any part of the digestive system, from the mouth to the anus. The NHS describes Crohn's disease as a lifelong condition characterised by periods of active disease (with symptoms such as diarrhoea, abdominal cramps, fatigue, blood in the stool, and unintended weight loss) and periods of remission, during which those symptoms ease significantly or disappear. Unlike ulcerative colitis, which is confined to the colon, Crohn's can cause deep, penetrating inflammation anywhere in the digestive tract.

Treatment typically begins with anti-inflammatory medicines and immunosuppressants. When those approaches fail to control the disease adequately, biologic medicines become the next option.

What Biologics Are

Biologics are a class of medicines produced from biological sources (typically proteins manufactured in laboratory cell cultures) that work by targeting specific molecules in the immune response driving Crohn's inflammation. The classes approved for Crohn's disease include:

• Anti-TNF agents (infliximab, adalimumab, certolizumab pegol): target tumour necrosis factor-alpha, a key inflammatory signalling protein
• Anti-integrin agents (vedolizumab): block immune cells from entering the gut by targeting a cell-surface protein called alpha-4 beta-7 integrin
• Anti-IL-12/23 agents (ustekinumab): target a shared subunit of two cytokines (interleukin-12 and interleukin-23) that drive inflammation
• Anti-IL-23 agents (risankizumab): specifically target interleukin-23, a cytokine increasingly recognised as central to intestinal inflammation in Crohn's

The Crohn's & Colitis Foundation notes that each class has a different efficacy and safety profile, and different administration routes: some are given as intravenous infusions in a clinic, while others are administered as subcutaneous injections at home.

What a Network Meta-Analysis Does

A standard meta-analysis pools data from trials comparing the same two treatments: for example, a biologic drug against placebo. A network meta-analysis goes further: it uses the mathematical relationships between all available trials to estimate how treatments would compare against each other, even when they have never been directly tested in a head-to-head randomised trial.

The 2026 Cochrane network meta-analysis (Gordon M et al., Cochrane Database of Systematic Reviews, 2026 Jun 23; pubmed:42333672) followed the pre-specified, independently reviewed methodology Cochrane reviews are known for: systematic searching across multiple databases, standardised risk-of-bias assessment for each included trial, and transparent certainty-of-evidence ratings using the GRADE framework (Grading of Recommendations, Assessment, Development and Evaluations). With 94 randomised controlled trials pooled, the analysis provides the most comprehensive comparative overview of biologic drugs in Crohn's disease available in the published literature.

Key Findings: Induction of Remission

For induction of remission (getting Crohn's disease under control in the short term), the Cochrane network meta-analysis found that ustekinumab emerged as the best-performing biologic, with high-certainty evidence of superiority over placebo. The relative risk was 2.01 (95% confidence interval 1.67 to 2.43), meaning patients receiving ustekinumab were approximately twice as likely to achieve remission as those receiving placebo during the induction phase.

High certainty in the GRADE framework means the reviewers are very confident that the true effect is close to the estimated effect. This is the strongest category available in a systematic review, indicating the conclusion is unlikely to be substantially changed by future research.

This finding positions ustekinumab ahead of the other biologics assessed in the network for short-term disease control in Crohn's. It is worth noting that a relative risk of 2.01, while high, also reflects that placebo remission rates in clinical trials are not zero: some patients improve without active treatment, partly due to natural disease fluctuation and partly due to the therapeutic effect of the trial setting. The clinical significance of the ustekinumab finding lies in how consistently and substantially it exceeds that background rate.

Key Findings: Maintenance of Remission

For maintenance of remission (keeping Crohn's disease in remission over the longer term, typically assessed at one year), the picture was different. The Cochrane network meta-analysis found that adalimumab (an anti-TNF biologic) was probably more effective than placebo for maintaining remission, with moderate-certainty evidence of benefit.

Moderate certainty in GRADE means the reviewers are reasonably confident in the estimated effect, but acknowledge that future studies may refine the estimate. The authors specifically highlighted the concomitant use of immunomodulators (such as azathioprine or 6-mercaptopurine) as an important confounding variable across maintenance trials, complicating direct comparisons.

The different picture for maintenance compared with induction reflects a genuine complexity in the evidence base: some biologics have been studied more extensively in maintenance than induction, and the populations and trial designs used for each phase differ. It does not mean adalimumab is the only or best maintenance option for every patient; it reflects where the highest-certainty evidence currently sits within the network.

What the Review Calls For

The authors concluded that the evidence base, while extensive, leaves important questions unanswered. They specifically called for future randomised trials that directly compare biologic agents against each other, rather than each against placebo alone, so that indirect network estimates can be replaced with direct head-to-head data. They also called for research that:

• Addresses the role of biosimilars, which have become an increasingly important part of biologic prescribing practice but are underrepresented in randomised trials
• Prioritises endoscopic remission outcomes (healing of the bowel lining, not only symptom resolution) as the primary measure of treatment success
• Collects longer-term safety data extending beyond the typical time frames of randomised controlled trials

These calls reflect the recognised limitations of network meta-analysis when the underlying trial network is incomplete: indirect comparisons carry more uncertainty than direct comparisons, and the conclusions are only as strong as the trials feeding into them.

What This Means for Patients

For people living with Crohn's disease who are approaching or already using biologic treatment, the 2026 Cochrane network meta-analysis provides several practically relevant messages.

Not all biologics are equivalent for induction. The high-certainty evidence for ustekinumab's induction efficacy stands out within the network. Patients and clinicians discussing which biologic to consider may find this comparative context useful, though individual factors including previous treatment history, administration preferences, access and availability, and the presence of extraintestinal manifestations (such as skin or joint symptoms) will always influence the decision in ways a meta-analysis cannot capture.

Maintenance evidence is more nuanced. Moderate-certainty evidence for adalimumab in maintenance is not the same as evidence that adalimumab is the only maintenance option. Long-term disease control involves factors beyond the clinical trial setting, including adherence, dose optimisation, and therapeutic drug monitoring, and the right maintenance approach depends on individual clinical circumstances.

Biosimilars are part of the treatment landscape. Biosimilars of approved biologics (including infliximab and adalimumab) are now widely available in many countries, often at lower cost. The Cochrane review's call for biosimilar-specific research reflects the fact that patients are increasingly receiving these medicines, and the evidence base has not kept pace with their adoption in practice.

Network comparisons are the best available, but not the same as direct trials. For patients preparing for a conversation with their gastroenterologist, it may help to know that this ranking comes from indirect statistical comparison, not a trial where patients were randomly assigned to ustekinumab versus adalimumab directly. The authors' call for head-to-head trials acknowledges this distinction, and future direct comparisons may shift the evidence in ways the current network cannot fully predict.