We read with great interest the prospective study by Yzet et al. demonstrating that intestinal ultrasound (IUS) transmural healing independently predicts long-term outcomes in Crohn's disease (CD) patients already in endoscopic remission 1. We wish to highlight three complementary perspectives that strengthen the clinical relevance of these findings while raising important methodological considerations. First, the prognostic value of transmural healing reported by Yzet et al. is further contextualised by a recent systematic review of 46 studies encompassing over 5500 patients, which found transmural healing to be associated with more pronounced reductions in hospitalizations, surgery, and relapse than mucosal healing alone 2. This benefit was observed across heterogeneous definitions and imaging modalities, supporting the biological plausibility of transmural healing as a target irrespective of the assessment method used. Second, an open question is whether IUS alone is sufficient to define transmural healing, or whether combining it with faecal calprotectin improves prognostic accuracy. Huet et al. recently demonstrated in a prospective cohort of 112 CD patients that the combination of normal IUS and normal faecal calprotectin—defining true transmural healing—was associated with substantially lower risks of bowel damage progression and relapse-related drug discontinuation compared to either tool alone 3. Notably, IUS was better accepted by patients than faecal calprotectin (9.6 ± 0.8 vs. 7.9 ± 2.3 on a 10-point scale, p < 0.0001) 3. This composite non-invasive strategy, previously validated for mucosal healing assessment by the same authors 4, may represent a pragmatic monitoring pathway for daily practice. Third, while Yzet et al. acknowledge the absence of centralised IUS reading as a limitation, broader implementation concerns deserve emphasis. Reliable transmural assessment requires structured training—basic IUS proficiency demands a minimum of 75–112 supervised examinations even for experienced ultrasonographers 5—and intermodality agreement between IUS and MRE for transmural response remains only fair-to-moderate (κ = 0.43) 6. Standardisation of both operator training and imaging protocol will be prerequisites before IUS transmural healing can become a robust treatment target in CD 7-9. These considerations are directly relevant to the ongoing VECTORS trial (NCT06257706), a randomised phase 4 study comparing an IUS-inclusive treat-to-target strategy against a symptom- and biomarker-based approach alone in 304 patients with moderately-to-severely active CD 10. Its results will be crucial to determine whether the prognostic signal demonstrated by Yzet et al. translates into a clinically actionable therapeutic benefit—and whether IUS can finally be established as a formal treatment target in CD. Luisa Bertin: conceptualization, investigation, writing – original draft. Edoardo Vincenzo Savarino: writing – review and editing, validation. The authors have nothing to report. Edoardo Vincenzo Savarino has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr. Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapagos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, MayolyBiohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Unifarco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, DiademaFarmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici. Luisa Bertin has served as speaker for Edra SPA, Takeda. This article is linked to Yzet et al. papers. To view this article, visit https://doi.org/10.1111/apt.70479. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Bertin et al. (Fri,) studied this question.