Landmark IBD trials

ADMIRE CD II95% CI

+2.4 points (95% CI −5.8 to 10.6)

In the larger confirmatory trial, darvadstrocel was no better than placebo for complex perianal fistulas when both arms had surgical preparation.

Clinical remissionWeek 12 · both guselkumab groups pooled

Adjusted difference +21 points (95% CI 14–28); P<0.0001

Guselkumab can be started with subcutaneous 400 mg injections instead of IV infusions, with clear benefit over placebo by week 12.

Endoscopic responseWeek 14

Posterior mean difference vs placebo: 450 mg 13% (95% credible interval −3 to 29); 900 mg 33% (16 to 50)

Duvakitug, an anti-TL1A antibody, gave a dose-related endoscopic response signal in Crohn's disease in phase 2b; phase 3 trials will decide whether TL1A becomes a new Crohn's disease target.

Clinical remissionWeek 14 · modified Mayo score

Posterior mean difference vs placebo: 450 mg 15% (95% credible interval −3 to 33); 900 mg 26% (8 to 44)

Duvakitug, an anti-TL1A antibody, showed a dose-related remission signal in UC in phase 2b; phase 3 trials will decide its place.

Steroid-free clinical remissionWeek 48 · PRO2 remission, calprotectin below 250 µg/g, no steroids

Difference 4%; P=0.5

After secondary loss of response to ustekinumab, IV reinduction plus every-4-week dosing is no better than reinduction plus every-8-week dosing, and few patients regain remission either way.

Endoscopic remissionMayo endoscopic subscore 0

Endoscopic remission 37.5% vs 15.1%; +22.4 points (95% CI 5.3–39.5)

Adding 8 weeks of upadacitinib to vedolizumab induction improved early endoscopic remission over vedolizumab alone, but this small open-label trial is hypothesis-generating.

Combined remission95% CI

Combined remission 62% vs 25%; OR 5.1 (95% CI 1.07–24.4)

In a small trial, ustekinumab after surgical drainage improved short-term combined clinical and MRI remission of perianal fistulas, but the effect was uncertain by week 48.

Treatment failureWeek 52 · composite; lower is better

Treatment failure 53.3% vs 81.5% at week 52; P=0.03

After a steroid-responsive episode of acute severe UC in a thiopurine- and biologic-naive patient, starting infliximab plus azathioprine reduced 1-year treatment failure compared with azathioprine alone.

Difference, percentage points95% CIs

Week-10 co-primaries missed; both met at week 58 in responders

Filgotinib failed its week-10 induction endpoints in Crohn's disease, unlike upadacitinib in its own phase 3 trials, so JAK inhibitors should not be assumed to work equally well in Crohn's disease.

Sustained clinical remission12 months

Sustained remission 84% vs 76% at 12 months; P=0.2

In carefully selected patients in deep remission who stay on an immunomodulator, stopping the anti-TNF did not significantly reduce 1-year sustained remission, but calprotectin rose more often; withdrawal is an option to discuss, not a default.

Response + clinical remissionGALAXI-2 · weeks 12 and 48

GALAXI-2 response + remission 55% (200 mg) vs 12% placebo; P<0.0001

IV guselkumab induction followed by SC maintenance is effective in Crohn's disease and outperformed ustekinumab at week 48 on several endpoints.

Clinical remissionWeek 12 · both guselkumab groups pooled

Week-12 remission 56.1% vs 21.4%; endoscopic response 41.3% vs 21.4%

Guselkumab can be given entirely by subcutaneous injection for both induction and maintenance in Crohn's disease, with no IV infusion needed.

Maximal bowel wall thickness above 6 mm on ultrasoundRelative risk, 95% CIs

Bowel wall over 6 mm: preterm birth RR 4.01 (95% CI 1.26–12.72)

In pregnancy, inflammation seen on intestinal ultrasound was associated with preterm birth, low birth weight and pre-eclampsia independently of symptoms and calprotectin; consider ultrasound to monitor IBD antenatally.

Clinical remissionInduction · week 12

Adjusted difference 15% (95% CI 10–20); P<0.0001

Guselkumab induces and maintains remission in UC, and the follow-up ASTRO trial showed induction can be given subcutaneously.

Primary result

Probability of a lower modified Rutgeerts score with vedolizumab than placebo: 77.8% (95% CI 66.4–86.3); P<0.0001.

Starting vedolizumab within 4 weeks of ileocolonic resection reduces early endoscopic recurrence in patients at risk.

Total Mayo score · primary endpointRisk difference, percentage points, 90% CIs

Primary endpoint missed at every dose; 90% CIs cross zero

Afimkibart missed its phase 2b primary endpoint (total Mayo remission), although remission by the modified Mayo score favoured it; anti-TL1A therapy still needs phase 3 proof.

Clinical remissionWeek 12 · cohort 1, all patients (135)

+25 points (95% CI 14–37); P<0.001

Anti-TL1A therapy is a new mechanism in UC; tulisokibart produced a large placebo-adjusted remission rate in a short phase 2 trial, with phase 3 results still awaited.

Clinical remissionWeek 12 · induction (INSPIRE)

Induction remission 20.3% vs 6.2%; maintenance 40.2% (180 mg) vs 25.1%

Risankizumab induces and maintains remission in UC, including after advanced-therapy failure, and many week-12 non-responders respond to extended induction.

Clinical remissionWeek 54

P<0.0001

After IV infliximab induction, subcutaneous infliximab 120 mg every 2 weeks maintains remission and endoscopic response in Crohn's disease, an option for patients who prefer injections to infusions.

Clinical response by day 7First dose 10 vs 5 mg/kg

Risk ratio adjusted for thiopurine history 1.06 (95% CI 0.94–1.20); P=0.32

In steroid-refractory acute severe UC, a 10 mg/kg first infliximab dose or an accelerated schedule was not better than standard 5 mg/kg dosing.

Sustained steroid- and surgery-free remissionTo week 48

Absolute difference 64 percentage points (95% CI 57–72); P<0.0001

In newly diagnosed active Crohn's disease, starting infliximab plus an immunomodulator straight away gives far better 1-year and 5-year outcomes than step-up care.

Endoscopic remissionWeek 48 · SES-CD ≤4

Adjusted difference +15.6 points (95% CI 8.4–22.9); P<0.001

After anti-TNF failure, risankizumab beats ustekinumab for endoscopic remission, so an IL-23 p19 inhibitor is the stronger second-line choice of the two.

Endoscopic recurrence6 months

Relative risk 0.985 (95% CI 0.663–1.464); P=1.0

Removing more mesentery at primary ileocolic resection did not reduce 6-month endoscopic recurrence, and leaks were numerically more common.

Response by day 7Primary endpoint

OR 3.42 (95% CI 1.37–8.48); P=0.007

Adding tofacitinib to IV steroids improved day-7 response in acute severe UC in one small single-centre trial; promising, but not yet standard care.

Endoscopic-response compositeWeek 12 response + week 52 endoscopic response

Endoscopic-response composite 38.0% vs 9.0%; CDAI-remission composite 45.4% vs 19.6%

Mirikizumab, an IL-23 p19 inhibitor, induces and maintains clinical and endoscopic response in Crohn's disease, including after biologic failure.

mPDAI remission95% CI

mPDAI remission 31% vs 10% at week 14; +21 points (95% CI 5–38)

Vedolizumab is the first advanced therapy shown in a randomised trial to induce remission in chronic pouchitis.

Clinical remissionUC 52 · week 52, treat-through

Week-52 remission 32% vs 7% in a treat-through design; P<0.0001

Etrasimod, a once-daily oral S1P modulator, induces and maintains remission in UC, shown in a stricter treat-through design.

LUCENT-1 inductionClinical remission, week 12 · 300 mg IV every 4 weeks

P<0.001

Mirikizumab, an IL-23 p19 antibody, induces and maintains remission in UC and improves bowel urgency.

Relapse by 2 yearsCo-primary endpoint

Stop infliximab vs continue both: HR 3.45 (95% CI 1.56–7.69)

If you de-escalate combination therapy in stable Crohn's disease, stop the immunosuppressant, not infliximab; relapse is much less likely.

U-EXCEED endoscopic responseWeek 12 · biologic failure

Endoscopic response after biologic failure 34.6% vs 3.5% at week 12 (P<0.001)

Oral upadacitinib induces and maintains clinical remission and endoscopic response in Crohn's disease, including after biologic failure, with JAK-class safety issues to monitor.

Adjusted difference, percentage points80% CIs

Combination vs golimumab +22.1 points; vs guselkumab +8.5 (80% CIs)

Combining an anti-TNF with an IL-23 antibody for induction outperformed golimumab alone but did not clearly separate from guselkumab alone; this phase 2 signal needs phase 3 confirmation.

CDAI clinical remissionADVANCE · week 12

ADVANCE CDAI remission 45% (600 mg) vs 25%; all co-primaries met

IV risankizumab induction works in both biologic-naive and biologic-experienced Crohn's disease, with endoscopic response rates well above placebo.

CDAI clinical remissionWeek 52 · co-primary in the US protocol

Endoscopic response 47% (360 mg) vs 22% after withdrawal at week 52

SC risankizumab maintains remission and endoscopic response in Crohn's disease, with 360 mg every 8 weeks giving the most consistent benefit.

Response and remission95% CI

−0.9 points (95% CI −8.7 to 6.8)

Etrolizumab, an anti-β7 integrin antibody, did not beat infliximab in anti-TNF-naive UC, and it never became a treatment option.

Primary result

Least-squares mean change −2.9 (100 mg), −3.2 (50 mg) and −3.1 (25 mg) vs −1.9 (placebo); P=0.0039, P=0.0003 and P=0.0010 vs placebo

Obefazimod is a first-in-class oral drug with a new mechanism that improved UC activity in phase 2b; its place will depend on the phase 3 ABTECT results once they are published.

Radiological healingMRI at 18 months

P=0.005

For a high perianal fistula with a single internal opening, surgical closure after seton and short anti-TNF gives more MRI healing and fewer reinterventions than anti-TNF alone, and MRI healing predicts durable closure.

Clinical remission95% CI

+4 points (95% CI −6 to 14)

In biologic-naive moderate-to-severe Crohn's disease, ustekinumab was not superior to adalimumab monotherapy at 1 year and both worked well, so choose by patient factors, safety and preference.

Clinical remissionWeek 4

Remission 44% vs 44% at week 4; endoscopic response 43% vs 39% at week 12

Extra-intensive adalimumab induction does not beat the standard 160/80 mg regimen, and proactive TDM-guided maintenance was no better than dosing adjusted to symptoms and CRP.

Endoscopic responseSES-CD down ≥50%

Endoscopic response 38% vs 30% at week 48; P=0.087

With ustekinumab, an endoscopy-driven treat-to-target algorithm did not improve 48-week endoscopic response over clinically driven care; treat-to-target only helps if escalation has something to add.

Obstructive symptoms improved14-day symptom score down ≥1 point

OR 2.10 (95% CI 0.73–6.01); P=0.17

Symptomatic Crohn's strictures with active inflammation often respond to adalimumab; intensifying therapy did not significantly improve symptoms; secondary results on treatment failure and MRI stricture appearance favoured it but are hypothesis-generating.

U-ACHIEVE inductionWeek 8

Adjusted difference 21.6% (95% CI 15.8–27.4); P<0.0001

Upadacitinib 45 mg for 8 weeks, then 15 mg or 30 mg daily, gives some of the highest placebo-adjusted remission rates of any UC therapy.

Clinical remissionCDAI ≤150

+13.7 points (95% CI 3.8–23.7); P=0.008

After two IV doses, vedolizumab 108 mg SC every 2 weeks maintains remission in Crohn's disease better than placebo, so patients can switch to home injections.

Symptomatic remissionWeek 6

P=0.77; Specific Carbohydrate Diet not superior

In adults with mild-to-moderate Crohn's symptoms, the restrictive Specific Carbohydrate Diet was no better than a Mediterranean diet, so the easier, healthier Mediterranean diet is the reasonable default.

RemissionWeek 48

Remission 80.4% vs 54.3% at week 48; difference 26.1% (95% CI 7.7–44.5)

Stopping infliximab in UC remission lowered remission at week 48 (54.3% vs 80.4% when continued), although most patients respond to retreatment; continue anti-TNF therapy unless there is a strong reason to stop.

Sustained disease controlNo disease worsening over 52 weeks

Adjusted difference 17.6% (95% CI 9.0–26.2); P<0.001

In patients on maintenance infliximab, scheduled drug-level monitoring with a dosing algorithm kept more patients in sustained disease control over a year than standard dosing without levels.

Any infant infection in year 1 · adjusted odds ratioRatio, 95% CIs

No increase in any primary outcome with drug exposure

Biologics and thiopurines, alone or together, did not increase pregnancy or infant harms; active disease did, so continue effective therapy through pregnancy.

Induction A: biologic-naiveWeek 10

Difference 10.8% (95% CI 2.1–19.5); P=0.0157

Filgotinib 200 mg induces and maintains remission in UC, but it is not available in Canada; it matters here mainly as evidence for the JAK class.

Clinical remissionWeek 10 · induction

Remission 18.4% vs 6.0% at week 10 and 37.0% vs 18.5% at week 52

Ozanimod, a once-daily oral S1P receptor modulator, induces and maintains remission in UC with a low serious-infection rate.

Increased bowel wall thickness, % of patientsWeek (0 = at flare) 0 to 12

Sigmoid thickening 89.3% at flare, 38.6% by week 2 (P<0.001)

Intestinal ultrasound shows bowel wall thickening in most UC flares and tracks response within 2 weeks, so it is a practical point-of-care tool for monitoring UC treatment.

Clinical remissionWeek 52

SC vs placebo +32.3 points (95% CI 19.7–45.0); P<0.001

After two IV induction doses, vedolizumab can be maintained with 108 mg subcutaneous injections every 2 weeks, with remission rates numerically similar to IV.

Tolerated the dietPrimary endpoint

P=0.002; odds ratio 13.92 (95% CI 1.68–115.14)

In children with mild to moderate Crohn's disease, CDED plus partial enteral nutrition is better tolerated than exclusive enteral nutrition and gives more sustained remission at 12 weeks.

Sustained steroid-free remissionAt every visit, weeks 8–72

P=0.002

In children on adalimumab, proactive trough monitoring with dose adjustment to 5 µg/mL kept far more patients in steroid-free remission than reactive testing.

Primary non-response at week 14 · odds ratio for week-14 drug levelRatio, 95% CIs

Week-14 drug level and non-response: OR 0.35 (infliximab), 0.13 (adalimumab)

Anti-TNF failure in Crohn's disease is common and is driven largely by low drug levels and immunogenicity; an immunomodulator reduces antibodies, and primary non-responders need a change, not more of the same.

Clinical remissionWeek 8 · induction

Remission 15.5% vs 5.3% at week 8; 43.8% vs 24.0% at week 44 (every 8 weeks)

Ustekinumab, an IL-12/23 antibody, induces and maintains remission in UC with a reassuring safety profile.

Clinical remission95% CI

+8.8 points (95% CI 2.5–15.0)

In the first head-to-head biologic trial in IBD, vedolizumab beat adalimumab for clinical remission and endoscopic improvement at 52 weeks in UC.

Sensitivity for extentPer-patient estimate, 95% CI

Difference 10% (95% CI 1–18); P=0.027

Both MR enterography and intestinal ultrasound detect small bowel Crohn's disease with high sensitivity; MR enterography maps extent somewhat more accurately, while ultrasound is a valid first-line, point-of-care alternative.

Mucosal healing, no deep ulcersWeek 48

Adjusted risk difference 16.1% (95% CI 3.9–28.3); P=0.010

Escalating therapy on biomarkers plus symptoms, rather than symptoms alone, gives more mucosal healing in early Crohn's disease.

Primary result

Mean IBDQ 178.1 (95% CI 171.1–185.0) after resection vs 172.0 (164.3–179.6) with infliximab; mean difference 6.1 points (95% CI −4.2 to 16.4); P=0.25.

For limited (40 cm or less), non-stricturing terminal ileal Crohn's disease that has failed conventional therapy, laparoscopic resection is a reasonable alternative to starting an anti-TNF.

Disease worsening95% CI

−4.4 points (95% CI −12.7 to 3.9)

Switching stable patients from originator infliximab to biosimilar CT-P13 is not inferior to staying on the originator; this underpins provincial biosimilar switching policies.

OCTAVE SustainRemission, week 52

P<0.001 for both doses vs placebo

Tofacitinib is an effective oral induction and maintenance therapy for UC, but its infection (especially zoster), cardiovascular and cancer signals shape who should receive it.

Intention to treat97.5% CI

+15.2 points (97.5% CI 0.2–30.3)

ADMIRE-CD suggested benefit from stem-cell injection for complex perianal fistulas, but the larger ADMIRE CD II was negative and the product has been withdrawn in the EU and was never approved in Canada.

Primary result

Median infant:mother drug ratio at birth 1.21 (95% CI 0.94–1.49) for adalimumab and 1.97 (1.50–2.43) for infliximab. Full result on the page.

At birth, infliximab levels in the newborn are about twice the mother's and adalimumab levels are similar or slightly higher; both take months to clear (infliximab longest), which matters for live vaccines; combination with a thiopurine raised infant infection risk.

Primary result

No difference: mean AUC 564.0 (SD 241.9) with infliximab vs 587.0 (SD 226.2) with ciclosporin; adjusted difference 7.9 (95% CI −22.0 to 37.8); P=0.603

In steroid-refractory acute severe UC, infliximab and ciclosporin are equally effective rescue therapies; choose by local experience, patient factors and the maintenance plan.

Clinical recurrence95% CI

+7.1 points (95% CI −1.3 to 15.5)

In patients at increased risk, postoperative infliximab roughly halves endoscopic recurrence but did not significantly reduce clinical recurrence by week 76, so endoscopic monitoring is still needed.

All patients95% CI

Adjusted HR 0.54 (95% CI 0.27–1.06); P=0.07

Postoperative mercaptopurine did not clearly prevent clinical recurrence overall; the benefit was confined to smokers, and stopping smoking matters more.

UNITI-1: anti-TNF failureClinical response, week 6

Week-6 response 33.7% vs 21.5% after anti-TNF failure; 55.5% vs 28.7% without

IV ustekinumab induction followed by SC maintenance is effective in Crohn's disease, with larger effects in anti-TNF-naive patients.

Endoscopic recurrenceRutgeerts ≥i2 at 18 months · lower is better

P=0.03

After resection, treating by risk and scoping at 6 months with step-up for recurrence beats drug prophylaxis alone; this is why we do a postoperative colonoscopy.

Primary result

66.0% (SD 14.0) at early-combined-immunosuppression practices vs 61.9% (SD 16.9) at conventional practices; adjusted difference 2.5% (95% CI −5.2 to 10.2); P=0.5169.

Early combined immunosuppression did not improve 1-year symptom remission but lowered 2-year surgery, admissions and complications, supporting early effective therapy.

Clinical and biochemical remission1 year

P=0.686

A one-time optimisation to an infliximab trough of 3–7 µg/mL is worthwhile (fewer relapses, lower cost when levels are high), but repeated proactive trough-based dosing did not increase 1-year remission.

Clinical remissionWeek 6

Week-6 remission 15.2% vs 12.1% (P=0.433); 26.6% vs 12.1% by week 10

After anti-TNF failure in Crohn's disease, vedolizumab missed its week-6 remission endpoint but showed benefit by week 10, so judge response later than with faster-acting drugs.

Clinical responseInduction · week 6 · two doses 2 weeks apart

P≤0.0001 for both doses vs placebo

Subcutaneous golimumab induces and maintains response in anti-TNF-naive UC; the remission and mucosal-healing benefit in maintenance was seen with 100 mg every 4 weeks.

Corticosteroid-free remissionWeek 16

Steroid-free remission 39.7% with combination vs 22.1% with infliximab alone

When starting infliximab in anti-TNF-naive UC, adding azathioprine improves steroid-free remission at 16 weeks (40% vs 22%).

Clinical responseWeek 6 · induction

Adjusted difference +21.7 points (95% CI 11.6–31.7); P<0.001

Vedolizumab, a gut-selective anti-integrin, induces and maintains remission in UC, with every-8-week IV maintenance as the standard.

Clinical remissionWeek 6 · induction, CDAI ≤150

Week-6 remission 14.5% vs 6.8%; week-52 remission 39.0% vs 21.6%

Vedolizumab works in Crohn's disease but slowly: modest at week 6, clearer by week 10 and in maintenance, so it suits patients who can wait for the effect.

Treatment failure95% CI

+6 points (95% CI −7 to 19)

Ciclosporin and infliximab perform similarly as rescue therapy for steroid-refractory acute severe UC, in the short and long term.

Primary result

52 of 115 patients relapsed over a median follow-up of 28 months; 1-year relapse rate 43.9% ± 5.0%.

About half of patients relapse within a year of stopping infliximab from combination therapy, but most regain remission on re-treatment, and biomarkers identify a lower-risk group.

Clinical remission, all patientsWeek 8

Remission 16.5% vs 9.3% at week 8 and 17.3% vs 8.5% at week 52

Adalimumab works in UC, but absolute remission rates are modest, especially after prior anti-TNF failure.

Corticosteroid-free remissionWeek 26

Steroid-free remission 56.8% (combination) vs 44.4% (infliximab) vs 30.0%

In thiopurine- and biologic-naive Crohn's disease, infliximab plus azathioprine beats either drug alone for steroid-free remission and mucosal healing.

Clinical responseWeek 8 · ACT 1

Week-8 response 69% (5 mg/kg) vs 37% placebo in ACT 1; P<0.001

Infliximab 5 mg/kg at weeks 0, 2 and 6, then every 8 weeks, induces and maintains response in moderate to severe UC; doubling the dose gave no consistent added benefit.