IBD Evidence

Treatment

Biologics and advanced therapies compared

For the first time, the comparative question — which drug, not whether a drug — has meta-analytic answers.

Updated 2 min read 40 citations Evidence strength 5/5

Wire endoscopy snare used for upper gastrointestinal and colonic polypectomy
Gilo1969 · CC BY-SA 3.0 · Wikimedia Commons

What changed

For two decades the evidence base was drug-versus-placebo, which told clinicians that biologics work and nothing about which to choose. Network meta-analysis has changed that by using shared comparators to rank therapies indirectly [1][4].

The practical consequence is that first-line choice can now be reasoned about rather than defaulted, and differences between agents on induction versus maintenance, and on efficacy versus safety, are visible.

Comparative efficacy of advanced therapies

The classes

Advanced therapy classes in IBD
ClassMechanismNotes
Anti-TNFBlocks tumour necrosis factor alphaLongest track record; immunogenicity is the main limitation
Anti-integrinBlocks leucocyte trafficking to the gutGut-selective, so favourable systemic safety
Anti-IL-12/23 and anti-IL-23Blocks interleukin signallingStrong efficacy and safety profile in recent comparisons
JAK inhibitorsSmall molecule, intracellular signallingOral and rapid; cardiovascular and thrombosis warnings
S1P modulatorsSequesters lymphocytes in lymph nodesOral; newer, less long-term data

Treat to target, not to symptoms

The most consequential shift in IBD management is that symptoms are a poor proxy for inflammation. People feel well with active inflammation and feel unwell in remission. Current European guidance therefore targets objective markers — faecal calprotectin, endoscopic healing — rather than how the patient reports feeling.

This is also the answer to the dietary question raised on the diet page: an intervention that improves symptoms without improving objective markers has not treated the disease.

When one drug is not enough

Dual biologic or combined small-molecule therapy has been assessed for refractory disease [3]. It remains a specialist decision with a limited evidence base, and it is where single-cell work characterising response heterogeneity [2] is most likely to change practice — by predicting which mechanism to target in a given patient rather than discovering it by sequential failure.

Common questions

Which biologic is best?
Network meta-analyses now rank them [1][4], and the right choice depends on disease location, severity, extraintestinal features and your own risk tolerance.
Can I stop once I am in remission?
Withdrawal carries substantial relapse risk. It is a decision to make with your team, based on objective markers rather than how you feel.
Are biologics dangerous?
They carry real risks, principally infection. Untreated inflammation also carries risk, and the comparison is between two risks rather than against zero.
What is calprotectin for?
A stool marker of intestinal inflammation. It is how "treat to target" is actually monitored.
Street view of the station pharmacy building in Bautzen, Germany
Fiver, der Hellseher · CC BY-SA 4.0 · Wikimedia Commons
The evidence behind this page A stacked bar showing the composition of the 40 publications cited on this page by study type. 40meta-analysis (40)
40 publications, 2015–2026. This is a largely observational base. It can establish that things occur together; it cannot settle which one causes the other. Source: this page’s own citation list, below.

References

Every citation below links to the original peer-reviewed record on PubMed or via DOI. Nothing here is a substitute for medical advice.

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