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Are we treating to the right target?

Nothing makes more sense than the ‘treat to target concept’ in IBD. Every patient is different, IBD is complex, keeping a close eye on response is central to the precision medicine paradigm and min-maxing healthcare resource. 

This is why the recent STARDUST study published in Lancet Gastro may have left a few people disappointed where it concluded that timely escalation of ustekinumab therapy for patients with Crohn’s disease, based on early endoscopic response, clinical symptoms, and biomarkers, did not result in significantly better endoscopic outcomes at week 48 than symptom-driven decisions alone. 

Is endoscopy (and the SES-CD) the right target to shoot for? The debate around endpoints is more nuanced in CD given its complexity but this study was intently skewed towards what the endoscopist could see and luminal disease. If the inclusion criteria were ‘evidence of bowel wall thickening as seen on US/CT/MRE’ and then adjustment of ustekinimab based on a change of +/-2mm (for example) in small bowel wall thickness what might the results have looked like? What kind of patients might the study have recruited instead? 

Taking a holistic view of bowel wall healing beyond ulceration (despite being logical) is controversial and seemingly an anathema to the FDA who have resisted the move towards imaging endpoints in clinical trials. While recommended in various guidelines and widely used (with MaRIA being the best evidenced) imaging is not seeing much love in clinical trials. But for patient populations with L2/L3 disease, sophisticated drug companies may want to start looking to assets and claims really tailored to more specific sub-populations and the corresponding tests that excel in that space. I’m not advocating using MRE for distal UC here. 

Intestinal ultrasound has taken the EU by storm and is set to see fervent adoption in North America in the next few years. Ultrasound was used to perform a sub-study in 82 subjects from the trial with luke-warm results. Early response could be seen in as little as 4 weeks but a study built around endoscopy necessarily disadvantages imaging and vice versa and with subtle colonic disease being prevalent, ultrasound is on the back-foot (METRIC showed both MRE and US being weaker in the colon). 

Perhaps gastroenterologists are breathing a sigh of relief at a 16-week follow up endoscopy not being mandatory but the results of this study will make many of us go back and revisit trial design. It’s likely the existing tests we have need to be combined in new ways specific to the specific disease phenotype for the precision medicine ‘dream’ to be made real. IBD is on the edge of a technical revolution with AI, genetic testing, cloud computing, and cheaper more accessible tests being increasingly available. Having the role of endoscopy questioned, in an otherwise completely sensible concept (treat to target), is no bad thing and I profoundly hope this does not deter similar studies in the future. 

About Motilent

Motilent is a medical imaging technology company that aims to make some of the latest and most exciting image analysis technologies available to the researchers who can use them to make the important scientific advances required to advance our understanding of gastrointestinal disease.

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