This is the first of a short year-end series for Atomic IBD. Next I will pull out a “top 10” of 2025 publications, then finish with a look ahead to 2026.
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2025 rebuilt the therapeutic hierarchy.
If the last decade was defined by the proliferation of biologic options, this year was defined by comparative data that clarifies how to use them. We did not just get new drugs; we got head-to-head evidence that challenged old defaults. The long-standing dominance of anti-TNF therapies as the undisputed first-line biologic standard faced its most significant erosion to date, driven by superiority rather than hype.
Sequencing became the story.
Crohn’s disease: IL-23 p19 becomes first choice
The p19 signal is now hard to ignore.
GALAXI (guselkumab vs ustekinumab) and SEQUENCE (risankizumab vs ustekinumab) did not just show non-inferiority; they showed that targeting IL-23 alone delivers stronger endoscopic outcomes than blocking IL-12 and IL-23 together.
In North America, the Middle East, and parts of Europe such as Germany, IL-23 therapy has displaced anti-TNF as the first-line standard for Crohn’s disease, after a period of drift toward first-line ustekinumab drawn by superior drug persistence (no meaningful immunogenicity) and fewer sequencing problems compared with anti-TNF.
Now the first-line move in Crohn’s is to risankizumab or guselkumab.
Induction without an infusion
Subcutaneous induction has arrived.
GRAVITI and ASTRO showed that fully subcutaneous induction with guselkumab is possible and highly effective in both Crohn’s disease and ulcerative colitis.
This matters for patients who want autonomy and for systems trying to decongest infusion centres, and it strengthens the “p19 first” argument for providers and payers who weigh logistics alongside outcomes.
It changes the practical conversation.
Biosimilars set a new cost floor
The revolution is not evenly distributed.
The arrival of biosimilar ustekinumab has created a price floor we have not seen before, with seven FDA-approved biosimilars entering the US market in 2025.
Europe is already leaning into this, having built experience with biosimilars a decade earlier.
For cost-sensitive systems, biosimilar ustekinumab and the established biosimilar adalimumab remain formidable gatekeepers.
After more than a decade, vedolizumab remains without a biosimilar.
Top-down Crohn’s strategy reaches scale
Top-down is finally being implemented.
I have argued for top-down therapy in Crohn’s disease since 2010, and it has been standard of care in Edinburgh for a decade once biosimilars made it cost-effective.
PROFILE, published in 2024, helped settle the debate: hitting hard early drives deeper remission and prevents complications.
In 2025, that evidence translated into wider implementation.
The debate is now about execution.
Crohn’s sequencing in 2025
The hierarchy is clearer than it has been for years.
Phenotype still matters, but the evidence now points to distinct starting choices for distinct problems. This is how I currently think about sequencing in Crohn’s disease.
1. Severe, fistulising, or extensive disease: infliximab plus azathioprine is still the heavyweight champion. Start here, stabilise, and keep the option to switch to subcutaneous infliximab and drop azathioprine later.
2. Moderate-to-severe luminal disease: a p19 inhibitor is now the evidence-based first choice, with better endoscopy, safety and persistence.
3. When cost drives the pathway: biosimilar ustekinumab or adalimumab remain excellent drugs. They are no longer the ceiling of efficacy, but they are a very high floor.
Biosimilar vedolizumab would be welcome, especially in light of the new LOVE-CD data, and VICTRIVA will teach us whether vedolizumab with an upadacitinib induction blast does the job.
Ulcerative colitis: more options, less consensus
UC pathways remain variable.
There are now many effective drugs, and pathways differ across the world and within regions, driven by cost, familiarity and guidelines. The result is a wide spread of “standard” practice, even among specialist centres.
Consensus sequencing remains limited.
· Biologics: infliximab (IV and subcutaneous), adalimumab, golimumab, vedolizumab, ustekinumab, mirikizumab, risankizumab, guselkumab.
· Small molecules: ozanimod, etrasimod, tofacitinib, filgotinib, upadacitinib
· Conventional options: azathioprine (for steroid-dependent UC when needed); don’t forget that many patients only ever need 5-ASA; optimize before moving on.
Small molecules in UC: clearer niches and one new signal
The post-tofacitinib landscape is settling.
In Europe, filgotinib has found its niche for moderate disease: cheaper, simple dosing, good efficacy, excellent persistence, and a favourable safety profile. Upadacitinib sits above it for moderate-to-severe UC, and increasingly for acute severe ulcerative colitis (ASUC). The ACESO trial is recruiting across the UK, testing whether adding upadacitinib to IV corticosteroids early on day one can reduce the need for rescue therapy or colectomy. S1P receptor modulators (ozanimod and etrasimod) remain effective and well-tolerated, but still lack a clear positioning statement in a crowded field.
Obefazimod is the new entrant to watch.
The ABTECT phase 3 induction results presented at UEG in October showed significant and clinically meaningful remission rates across a broad population, including patients who had failed multiple prior advanced therapies (including JAK inhibitors). It is a first-in-class oral miR-124 enhancer.
Maintenance data are eagerly awaited.
UC sequencing: still more opinion than algorithm
Every expert will tell you their opinion, often shaped by local access and precedent.
Options are excellent for clinicians and patients, but the practical requirement is to know the pros and cons of each drug and to be able to discuss them in shared decision-making. I am still not sure we know the right time to start advanced therapy in UC, and I see both delayed starts and arguably early starts.
Timing remains the hardest decision.
Global access: the widening gap
It is worth stepping back.
For much of the world, these choices do not exist. In many low- and middle-income countries, anti-TNF biosimilars are the ceiling, not the floor. In India, generic tofacitinib has flooded the market and become a de facto first-line advanced therapy, driven by cost and availability rather than sequencing logic.
The access gap is widening.
Prediction and personalisation
We still largely prescribe by phenotype and hope.
The promise of biomarkers to guide drug selection remains largely unfulfilled in 2025, though work continues.
More on this in a future post.
This needs its own discussion.
Comparative evidence: what to trust
We still need more comparative trials.
Network meta-analyses can be useful for hypothesis generation and to satisfy health technology assessment bodies, but they are not a substitute for real comparative data.
Real-world comparative effectiveness studies also need caution: very large datasets, for example TriNetX, cannot fully correct hidden bias and confounding even with propensity matching.
Expect big publications to point in different directions.
Blinded head-to-head studies still matter most.
Surgery: appendicectomy in UC
Appendicectomy returned to the UC conversation.
The ACCURE trial published in Lancet Gastroenterology & Hepatology showed that laparoscopic appendicectomy added to standard medical therapy significantly reduces clinical relapse at 12 months. COSTA data reinforced the signal, showing over 20% induction of remission compared with medical therapy alone. This may have been the most unexpected therapeutic development of the year.
More to come, including how we might identify who will respond.
Looking ahead
The next challenge is strategy.
What we really need are innovative trials that enable head-to-head comparisons, sequencing, add-ons and true combinations. Emerging concepts around combination strategies, such as DUET trial concepts and “induction blasting” with JAKs, suggest that for ceiling-hitters, 2026 might be the year of deliberate combinations.
But that is for another post.
Next: top publications of 2025, then a 2026 preview.
Photo of me in the Grey Corries by Colin Henderson
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