Tag Archives: ASUC

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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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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Hypercoagulation with Acute Severe Ulcerative Colitis (ASUC) Persists for Months

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BJ Griffiths et al. Clin Gastroenterol Hepatol 2025; 23: 1798-1807. Open Access (PDF)! Hypercoagulation After Hospital Discharge in Acute Severe Ulcerative Colitis: A Prospective Study

Methods: In this prospective study, twenty-seven adult patients with ASUC and 25 control patients with quiescent ulcerative colitis were recruited. Thrombin generation (endogenous thrombin potential), rotational thromboelastometry (EXTEM and FIBTEM maximum clot firmness), procoagulant factors, anticoagulant factors, and fibrinolytic markers were assessed for those with ASUC on admission (Day 1), Day 5, 4 weeks, and at 8–12 weeks. These assessments were performed on a single occasion for control patients.

Key findings:

Discussion:

  • “Patients with ASUC had a hypercoagulable profile on initial presentation to the hospital, before receipt of LMWH, which was consistently demonstrated by individual and global assays of coagulation. The most marked elevations of individual factors at presentation were seen in the levels of Clauss fibrinogen, platelets, VWF, and FVIII, alongside heightened
    levels of the inhibitors of fibrinolysis PAI-1 and TAFIa.”
  • “This hypercoagulable state persisted for many weeks after hospital discharge, with levels of FVIII, fibrinogen, VWF, and inhibitors of fibrinolysis (TAFIa) remained significantly elevated at all timepoints up to 12 weeks, compared with the control population. This is despite
    intensive treatment for ASUC in all patients.”
  • “VTE and pulmonary embolism are 1 of the leading causes of morbidity and mortality during IBD flare-ups. The findings from this study reinforce the importance of thromboprophylaxis administration to all patients with ASUC at first presentation to hospital.”

My take: This study is in adults; the risk of VTE is lower in children and guidance on VTE prophylaxis is not clear.

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Does Accelerated Dosing of Infliximab Work for Acute Severe Ulcerative Colitis?

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MC Choy et al. The Lancet Gastroenterology 2024; Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial

Methods: In this open-label, multicenter, randomized controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomization 1). Block randomization was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomization. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomized between day 3 and day 7 (1:1; randomization 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received
5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response.

Thus, this was the first RCT comparing an intensified induction strategy (IIS; 10 mg/kg infliximab at weeks 0 and 1, with the second dose given earlier if no clinical response), an accelerated induction strategy (AIS; 5 mg/kg infliximab at weeks 0, 1, and 3, with the second dose increased to 10 mg/kg and given earlier if no response), and a standard induction strategy (SIS; 5 mg/kg at weeks 0, 2 and 6; with an extra 5 mg/kg dose before day 7 if no
response) in steroid-refractory patients with ASUC.

Key findings:

  • There was no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups: 65% vs 61%
  • In patients with a baseline albumin of less than 25 g/L, a day 7 response occurred in nine (64%) of 14 patients in the 10 mg/kg group versus 14 (45%) of 31 in the 5 mg/kg group (RR 1·43, p=0·17)
  • In patients with a baseline CRP of 50 mg/L or higher, a day 7 response occurred in six (60%) of ten patients in the 10 mg/kg group versus eight (42%) of 19 in the 5 mg/kg group (RR 1·39, p=0·34)
  • The proportions of patients with clinical response at day 14: 74% in the IIS group, 73% in the AIS group, and 68% of 44 in the SIS group.
  • The clinical remission at month 3: 50% in the IIS group, 52% in the AIS group, and 48% in the SIS group
  • The steroid-free remission at month 3: 41% in the IIS group, 42% in the AIS group, and 41% in the SIS group
  • The endoscopic remission at month 3: 46% in the IIS group, 46% in the AIS group, and 48% in the SIS group
  • The colectomy rate at month 3: 7% in the IIS group, 19% in the AIS group, and 12% in the SIS group colectomy at month 3 were not significantly different between group (P=0.20)
  • The colectomy rate at month 12: 7% in the IIS group, 22% in the AIS group, and 15% in the SIS group colectomy at month 3 were not significantly different between group (p=0.13)
  • In post-hoc analysis of second-dose salvage strategies (among the group who had not responded at day7), a clinical response was observed in 19 (59%) of 32 patients who received a 10 mg/kg salvage dose versus nine (64%) of 14 who received a 5 mg/kg salvage dose (RR 0·92). Endoscopic remission at month 3 was observed in 11 (34%) who received 10 mg/kg salvage versus six (43%) who received 5 mg/kg salvage (RR 0·80). Colectomy by 3 months occurred in ten (31%) who received 10 mg/kg salvage compared with three (21%) who received 5 mg/kg salvage (HR 1·46)
  • Higher proportions of patients with clinical and biochemical remission between weeks 2 and 6 were apparent in the IIS and AIS groups versus the SIS group, but by 3 months, these differences were lost

My take: Intensified, accelerated, and standard induction regimens in the PREDICT-UC study did not result in a statistically-significant difference in clinical response by day 14 or in remission or colectomy rates by month 3. However, there are some important caveats:

  1. There appeared to be a trend towards a lower colectomy rate in the IIS group.
  2. There appeared to be a favorable trend towards an improved response to IIS group in those with low albumin (<25 g/L) and high CRP (>5 mg/L). The smaller numbers in these subgroups could have precluded statistical significance
  3. Also, even the SIS group were able to receive a 4th induction 5 mg/kg dose between days 3-7 if they had not responded to treatment
  4. In patients who had not responded to either 10 mg/kg or 5 mg/kg, a salvage dose at day 7 resulted in a >60% response rate
  5. It is possible that a sustained strategy of more aggressive dosing (not done in this study) aided with therapeutic drug monitoring could result in better outcomes following IIS