Tag Archives: Crohn’s disease

Longer Adalimumab Dosing Intervals Associated with Worse Outcomes for Crohn’s Patients in Remission (LADI Trial)

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LMA Van Lierop et al. Gastroenterol 2026; 170: 404-407. Open Access! Long-Term Outcomes of Increased Versus Conventional Adalimumab Dose Interval for Patients With Crohn’s Disease in Stable Remission: 3-Year Follow-Up of the Randomized Controlled LADI Trial

Methods: “The LADI trial enrolled adults with luminal CD in corticosteroid-free clinical (CFCR) and biochemical remission, on adalimumab, 40 mg every 2 weeks. After randomization in a 2:1 ratio, the intervention group started on a 3-week interval and increased to 4 weeks, if in clinical and biochemical remission at week 24. The control group remained on adalimumab biweekly…The primary end point in this long-term follow-up (LTFU) study was the proportion of patients in CFCR (Harvey Bradshaw Index [HBI] <5 or remission per Physician Global Assessment [PGA] without systemic corticosteroids) without complications at year 3, on the assigned adalimumab interval.”

Key findings:

  • The proportion of patients achieving the primary end point was 34 of 95 (35.8%, intervention) vs 41 of 48 (85.4%, control; P < 0.001).
  • At year 3, 39 of 95 (41.1%) in the intervention group remained on the randomized or further de-escalated adalimumab regimen
  • Kaplan-Meier analyses of secondary end points showed the following probabilities at year 3 (intervention vs control) (Figure 1): remaining on the assigned adalimumab dose, 41.4% vs 91.4% (P < .0001); remaining on adalimumab, 83.7% vs 95.8% (P = .026); corticosteroid-free survival, 87.4% vs 95.7% (P = .062); and complication-free survival, 83.2% vs 97.9% (P = .015)
Kaplan-Meier curves visualizing maintenance of assigned dosing at baseline, continued adalimumab therapy, and corticosteroid-free survival in both groups. (A) Probability of maintaining assigned adalimumab dosing interval of 3–4 weeks (intervention) vs 2 weeks (control).
(B) Probability of remaining on adalimumab therapy over time.
(C) Probability of remaining in corticosteroid-free remission.

My take: About 60% of patients were unable to de-escalate their adalimumab dosing interval. Suboptimal dosing increased the risk of complications and having adalimumab therapy become ineffective.

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PREdiCCt Trial: Lower Calprotectin Targets in Crohn’s Disease and Ulcerative Colitis

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Constantine-Cooke N, Gros B, Plevris N, et al Gut 2026. doi: 10.1136/gutjnl-2025-337846. (Open Access!) Associations between demographic, clinical and dietary factors and flares in inflammatory bowel disease: the PRognostic effect of Environmental factors in Crohn’s and Colitis (PREdiCCt) prospective cohort study

Methods: Multicentre, prospective cohort study conducted across 47 UK centres. Patients with Crohn’s disease (CD), ulcerative colitis (UC) or IBD unclassified (IBDU) in self-reported remission were prospectively followed up. 2629 participants (1370 CD; 1259 UC/IBDU) – followed up for a median of 4.1 years.

Key findings:

  • Baseline FC was strongly associated with patient-reported flares (FC ≥250 µg/g: adjusted HR (aHR) 2.22; FC 50–250 µg/g: aHR 1.52 (reference <50 µg/g)).
  • Baseline FC was also strongly associated with objective flares (FC ≥250 µg/g: aHR 3.25; FC 50–250 µg/g: aHR 1.98). Objective flares were “clinical flare plus C-reactive protein >5 mg/L and/or faecal calprotectin (FC) >250 µg/g with treatment escalation.” In ulcerative colitis, the probability of an objective flare within two years rose from 11% in those with baseline calprotectin below 50 µg/g to 34% in those above 250.
  • At 24 months, cumulative patient-reported and objective flare rates were 28% and 12% in CD, and 33% and 15% in UC/IBDU, respectively. Overall, patient-reported flares were more common (31%), while objective flares were less frequent (14%).
  • In UC, higher total meat intake was associated with increased risk of objective flares (highest versus lowest quartile: aHR 1.95, 95% CI 1.07 to 3.56). The absolute two-year risk rose from 12% in the lowest quartile of meat intake to 26% in the highest.
  • No consistent associations were observed for ultraprocessed foods, fiber or polyunsaturated fatty acids and flare.
Flares by faecal calprotectin (FC) stratified into FC < 50, 50 ≤ FC ≤ 250, and FC >250 μg/g. (A) Patient-reported flare in Crohn’s disease; (B) objective flare in Crohn’s disease; (C) patient-reported flare in ulcerative colitis/inflammatory bowel disease unclassified; (D) objective flare in ulcerative colitis/inflammatory bowel disease unclassified. aHR, adjusted hazard ratio.

My take: Lower calprotectin values, even in remission, are associated with better outcomes. Risk was meaningfully increased even in the 50–250 µg/g range, compared with levels below 50. Higher meat intake may increase the risk of flares for UC.

Summary of study information from Charlie Lees: The PREdiCCt Study: Can We Predict IBD Flares?

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Detecting Preclinical Crohn’s Disease in First-Degree Relatives with Biomarker Screening

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D Turner et al. . Gut 2025;0:1–7. doi:10.1136/gutjnl-2025-336368. Preclinical stages of Crohn’s disease defined by faecal calprotectin in asymptomatic first-degree relatives: screening framework for prevention trial

Methods: “Faecal calprotectin was measured in asymptomatic FDRs aged 6–38 years; those with persistent elevation, defined as >70 µg/g in at least two separate tests, were offered panenteric video capsule endoscopy or ileocolonoscopy”

Population: 331 (35%) first-degree relatives (FDRs) (from a group of 950) agreed to be screened: 63 (19%) had persistently elevated calprotectin, of whom 42 underwent further evaluation

Key findings:

  • From the initial screened cohort of 331 patients, nine (2.7%) had endoscopic appearance compatible with presymptomatic CD, and 22 (6.6%) had non-specific macroscopic mucosal changes
  • Median calprotectin was significantly higher in those with presymptomatic CD (772µg/g (IQR 279–1685)) compared with others (31µg/g (IQR 30–61), p<0.0001)
  • Calprotectin >225 µg/g predicted presymptomatic CD (area under the receiver operating
    characteristic curve 0.97 (95% CI 0.94 to 1.0; p<0.001; sensitivity 89%, specificity 94%)

Discussion Points:

  • “There is no universally accepted definition for preclinical stages of CD, and
    the distinction between these stages remains partly subjective.”
  • “The lack of longitudinal follow-up is also a limitation, but this will be completed as part of the PIONIR trial.”

My take (borrowed in part from the authors):

  1. Identification of pre-symptomatic CD “can facilitate designing targeted interventions and defining inclusion criteria for prevention trials.” The disease may be more modifiable in the early stages of disease.
  2. This trial suggests the calprotectin threshold of >70 is too low to target screening. For specificity, the study showed that persistent elevation above 225 merits investigation; though, it has been our practice to use a threshold of >150 for children older than 5 years.
  3. Approximately 5% of asymptomatic FDRs of CD patients have evidence of pre-symptomatic CD and approximately 10% more have non-specific mucosal changes when evaluated

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IBD Briefs: Upadcitinib in Children with Severe Colitis and Timing of Infliximab Switch to SC Route in Adults

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A Yerushalmy-Feler et al. Inflammatory Bowel Diseases, 2025, 31, 3320–3326. Real-World Experience with Upadacitinib for Pediatric Acute Severe Ulcerative Colitis: An International Multicenter Retrospective Study from the Pediatric IBD Porto Group of ESPGHAN

In this study of 22 pediatric patients with ASUC refractory to infliximab, key findings:

  • By week 26, 14 (64%) were in corticosteroid-free clinical remission and 16 (73%) patients remained colectomy-free
  • Two serious AEs of an appendiceal neuroendocrine tumor and cytomegalovirus colitis

My take: It is good to see more pediatric data. The availability of upadacitinib will likely lead to lower colectomy rates.

Related blog post: IBD Briefs: Upadacitinib in Children, Predicting Crohn’s Disease, and Autoimmune Diseases Associated with IBD

L Bertani et al. Inflammatory Bowel Diseases, 2025, 31, 3363–3369. When to Switch to Subcutaneous Infliximab? The RE-WATCH Multicenter Study

Methods: The RE-WATCH study was an observational, multicenter, retrospective study performed in four IBD referral centers. Inclusion criteria meant that only patients receiving on label SC-IFX at a dosage of 120 mg every other week were included in the study. The initiation of IFX therapy as the baseline timepoint.

Key findings:

  • There were no statistical differences between the two groups, early vs. late switch, after one year in terms of the respective endoscopic response (71.4% vs 70.8%, P = .95), steroid-free clinical remission (62.5% vs 68.7%, P = .51), or IFX retention rate (75.0% vs 66.7%, P = .35).
  • There was higher endoscopic remission rates in early switch patients as compared to late switch patients; however, this trend was not significant (69.6% vs 52.1%, P = .07).
  • A return to IV-IFX was required in 1 of 43 early switch patients and in 3 of 44 late switch patients (2.3% vs 6.8%, P = .31)
  • While the early switch group appears to fare a little better, there is likely a selection bias. For example, the early group had a much lower rate of severe endoscopic score at baseline (20% vs. 54%) and lower rate of Crohn’s fistulizing disease (8% vs 33%).
partial Mayo score (pMS)
Harvey–Bradshaw index (HBI)

My take: These results indicate that outcomes are similar between patients switching from to IFX SC at both early (after induction) and late (after 6 months).

It is worth noting that prior studies have shown that home-based therapies (eg. home infusion), compared to office-based therapies, have been “associated with suboptimal outcomes including higher rates of nonadherence and discontinuation of infliximab.” This is a concern for SC biologics as well.

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Effectiveness of Switch to Subcutaneous Infliximab

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N Mathieu et al. Clin Gastroenterol Hepatol 2025; 23: 2597 – 2606. Open Access! PErsistence and Safety of Subcutaneous Infliximab 1 Year After Switch From Intravenous Route in IBD Patients in REMission

Methods: The PEREM (PErsistence, effectiveness and safety of subcutaneous infliximab after switch from intravenous infliximab in IBD patients in REMission) study, a prospective national French cohort trial, enrolled 426 patients with IBD. Participants were in steroid-free clinical remission for at least 6 months on IV-IFX when they switched to SC-IFX. 56% were on IV-IFX standard dosing (5 mg/kg 8-weekly) and 16% received combination therapy with an immunomodulator drug at baseline. All patients were switched to SC-IFX standard dosing (ie, 120 mg every other week). The treatment could be intensified during follow-up, either to 120 mg every week or 240 mg every other week.

Key Findings:

  •  At week 48, SC-IFX persistence was 95.4%
  •  86.9% of patients were in steroid-free clinical remission
  • Mean infliximab levels were 8.0 μg/mL at inclusion and 18.0 μg/mL at week 48 (P < .0001)
  • Among the 19 (4.5%) patients who stopped SC-IFX, 6 (1.4%) switched back to IV-IFX
  • 23 (5.4%) patients required SC-IFX dose escalation
  • Dosing at 10 mg/kg/Q4W had 100% SC IFX persistence compared to 95% for 5 mg/kg/Q8W; however, at the 48 week followup, there were only 6 patients in the higher dose compared to 149 in the lower dose
  • Ongoing use of combination therapy was not associated with better persistence. Though, only 7 patients were receiving combination therapy at the 48 week followup

From the discussion:

  • “The high persistence observed in the PEREM study is partly explained by the long-term control of the disease by the time of switch, the median time since last flare being over 5 years before inclusion. Henceforth, the persistence observed here is in accordance with results on long term maintenance of IV-IFX, the yearly persistence of IV-IFX without intervention being 87%.”
  • SC-IFX was associated with higher levels. However, this was expected and higher levels are needed with SC administration. The “different bioavailability of SC-IFX compared with IV-IFX is responsible for different goals of infliximab blood levels depending on its route. In particular, a level above 20 μg/mL has been associated with higher rates of remission20” with SC-IFX.

My take: This study shows that SC-IFX is a good option for patients in long-term remission. With SC-IFX therapy, more effort is needed to make sure patients are adherent with therapy and monitoring in order to achieve optimal outcomes.

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Video Capsule Endoscopy in VEO-IBD — Is the Juice Worth the Squeeze?

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S-I Hagiwara et al.  Inflammatory Bowel Diseases, 2025; izaf144, https://doi.org/10.1093/ibd/izaf144. Open Access! Feasibility and Safety of Small Bowel Capsule Endoscopy in Very Early-Onset Inflammatory Bowel Disease: A Multi-Institutional Study

This article shows that video capsule endoscopy (VCE) (aka small bowel capsule endoscopy [SBCE]) is feasible in children with very early-onset inflammatory bowel disease (VEO-IBD). There were 82 patients (median age, 3.8 years; median body weight, 13.0 kg) who underwent 104 SBCEs. All capsules were deployed endoscopically. Gastrointestinal patency was assessed in 95% of procedures, most commonly using patency capsules (70%).

Key findings:

  • Observation of the entire small intestine was achieved in 100 (96.1%) patients
  • Of the remaining 4 patients, 3 could not undergo a complete observation of the entire small intestine due to battery depletion, and 1 had the capsule retained in the stomach
  • Abnormal small bowel findings were observed in 42% of patients, with aphthae being the most common (34%), followed by ulcers (18%)

In their discussion, the authors note that due to young age, the capsules and the patency capsules required endoscopic deployment (best in duodenum). Thus, most patients received general anesthesia or intravenous sedation twice within a short period.

The authors note that “SBCE has been reported to be superior to MRE in detecting superficial mucosal activity… [and] offers a radiation-free, relatively well-tolerated, and highly sensitive method for mucosal evaluation in VEO-IBD.”

My take: Given the typical use of a patency capsule and thus the need for two separate anesthesia dates, I doubt the “juice is worth the squeeze” in utilizing SBCE for most patients VEO-IBD.

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Useful repurposing of phone booth in Cotwolds, UK

Postoperative Outcomes with Tofacitinib Following Colectomy for ASUC and Real-World Outcomes for Upadacitinib in Crohn’s Disease

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C Larson et al. Clin Gastroenterol Hepatol 2025; 23: 2263-2271. Postoperative Outcomes in Tofacitinib-Treated Patients With Acute Severe Ulcerative Colitis Undergoing Colectomy

This  was a multicenter, retrospective, case-control study of patients hospitalized with ASUC who underwent colectomy, comparing patients treated with tofacitinib (n=41) prior to colectomy with infliximab-treated controls (n=68).

Key findings:

  • Compared with tofacitinib-treated patients, infliximab-treated patients had higher overall rates of overall (44 [64.7%] vs 13 [31.7%]; P = .002) and serious (19 [27.9%] vs 3 [12%]; P = .019) postoperative complications

My take: This study supports the safety of JAK inhibitor therapy for ASUC. It showed a significantly lower rate of overall postoperative complications in ASUC patients treated with tofacitinib compared with infliximab; the authors note that “these findings can likely be extrapolated to upadacitinib, a selective JAK inhibitor, given its similar mechanism of action.”

J Devi et al. Clin Gastroenterol Hepatol 2025; 23: 2281-2291. Open Access! Real-World Effectiveness and Safety of Upadacitinib in Crohn’s Disease: A Multicenter Study

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Spotlight: AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

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Yesterday’s post (AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease) summarized the following article:

The associated “Spotlight” provides useful a graphic summary. Here is most of the information:

AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

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FI Scott et al. Gastroenterology, Volume 169, Issue 7, 1397 – 1448; Open Access! AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn’s Disease

The guideline panel agreed on 16 recommendations. This highly-detailed report provides a comprehensive, patient-centered, evidence-based approach to the pharmacologic management of adult patients with moderate-to-severely active CD. Table 1 summarizes this lengthy 53-page report. Tomorrow’s post will be the “spotlight” summary which presents the recommendations in easier to read graphic.

Key Points:

The guidelines are overall very helpful. They identify higher efficacy medications and recommend them. In addition, they support the use of combination therapy with thiopurines (which are less frequently used in pediatrics). It is interesting that the sixteenth recommendation clashes with prior expert recommendations. The sixteenth recommendation in this report makes no recommendation on using endoscopic surveillance compared to symptomatic clinical remission. Most experts advise “treat-to-target” therapy approaches.

In the discussion of this, the authors state the followiing:

“Recent position statements from an international consortium of experts have advised that longitudinal targets for the management of IBD should include not only clinical remission but also endoscopic resolution of inflammation.31 Several studies have demonstrated that patients who achieve endoscopic remission (vs those with ongoing endoscopic activity) have favorable long-term outcomes…

There are limited RCTs assessing whether there is actual benefit in systematically treating toward endoscopic remission target vs symptomatic remission targets (ie, testing whether the target has been achieved, followed by algorithmic treatment adjustment, including escalating index therapy, adding an immunomodulator, followed by switching to an alternative advanced therapy and surgery). There was significant heterogeneity among the 2 reviewed studies, both in terms of the advanced therapy used, algorithms for therapy modification, and the cadence and frequency of endoscopic monitoring that challenge interpretation. Based on the significant uncertainty of evidence with regard to improving maintenance of remission or reducing the risks of adverse events, the guideline panel could not make a recommendation in relation to selecting endoscopic targets over clinical targets.

It is worth emphasizing that in both of the included trials, the majority of individuals in the endoscopic healing arms were not able to meet the goal of endoscopic healing despite an algorithmic approach. For example, in STARDUST, only 11% of individuals achieved endoscopic remission.149…There are specific patient populations, such as those who have recently undergone intestinal resection,155 in which endoscopic evaluation may be particularly valuable in clinical decision making...

The benefit of a monitoring strategy incorporating biochemical monitoring over clinical monitoring alone was demonstrated in the CALM trial,152 and has been addressed in previous AGA guidelines on the role of biomarkers in patients with CD.12“

My take: These “living” guidelines are likely to be quite influential in selecting Crohn’s disease therapy. In pediatrics, ImproveCareNow provides a similar role of guiding treatment.

Related blog posts:

Guidelines for UC:

Crohn’s Disease:

Outcomes of Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease

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A Baccarella et al. Clinical Gastroenterology and Hepatology; 2025; 23: 2242 – 2252. Open Access! Outcomes of Allogeneic Hematopoietic Stem Cell Transplant in Monogenic Inflammatory Bowel Disease

This was a retrospective single-center (CHOP) study of 25 children with monogenic IBD who underwent Hematopoietic Stem Cell Transplant (HSCT) (2012-2022).

Key findings:

  • Seventy-two percent of patients had Crohn’s Disease, and 28% were classified as IBD-unspecified. Ninety-two percent of patients had VEO-IBD, 56% presenting under age 1
  • At most recent follow-up, 92% of patients achieved sustained medication-free remission of IBD and 60% with prior ostomy underwent re-anastomosis. There was 100% survival at a median follow-up of 3 years
  • There was significant improvement in growth, hospital days, and severe infections
Disease activity scores at the time of IBD presentation, immediately prior to transplant, 1-year post-transplant, and at most recent follow up if ≥2 years since transplant.

Discussion points:

  • “Delay of HSCT with the goal of obtaining remission of IBD prior to transplant may prove to be determinantal, as outcomes of HSCT are in general improved for younger patients,20 and medical remission is often unattainable for more severe forms of monogenic IBD. Within our cohort, 32% of patients had moderate or severe disease at the time of transplant despite medical optimization. None of these patients developed intestinal GVHD, which was a rare event in our total cohort”
  • “HSCT is not without risk, and complications occurred in our cohort, at rates typical of other IEI cohorts”
  • “The selection of patients who would benefit from HSCT requires multidisciplinary discussion.”

With regard to patient selection, one item that was not included in the discussion was the one patient excluded from their analysis who had a TTC7A gene defect. In the results section, it was explained that the patient with “TTC7A was subsequently excluded as transplant was performed for the indication of SCID alone, rather than treatment of intestinal disease.” More discussion on this point is merited as many centers would NOT have a patient with TTC7A undergo HCST specifically because it cannot correct the underlying bowel disease.

Also, it was noted that one patient with CTLA4 deficiency had undergone HSCT prior to the discovery of the genetic defect. With the more widespread use of genetic testing available now, this discovery may have obviated the need for HSCT as treatment with abatacept is typically effective.

My take: Overall, the authors present impressive results for HSCT for monogenic IBD and strengthen the need for genetic testing in those with early onset disease and those refractory to treatment.

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