International experts, including an Australian gastroenterologist, have updated treat-to-target recommendations for Crohn’s disease and ulcerative colitis.
Gastroenterologists should reconsider when to escalate treatment for inflammatory bowel disease, with updated international recommendations warning that pursuing deeper remission does not always lead to better patient outcomes.
The updated STRIDE-III recommendations, published in The Lancet Gastroenterology & Hepatology, establish a framework for managing Crohn’s disease and ulcerative colitis that distinguishes between treatment targets requiring therapeutic intervention and those that may not justify changing medications.
Australian gastroenterologist Professor Rupert Leong, from Concord Repatriation General Hospital and the University of Sydney, was among the international experts involved in developing the recommendations.
The guidance, developed through the International Organisation for the Study of Inflammatory Bowel Disease (IOIBD), builds on the STRIDE-II recommendations published in 2021.
Researchers reviewed 1018 studies, including 462 focused exclusively on Crohn’s disease, 335 on ulcerative colitis, and 221 involving mixed populations.
The evidence was combined with surveys of 60 international IBD specialists and 23 paediatric gastroenterologists, followed by a modified Delphi consensus process.
A key change is the introduction of three categories of treatment targets – actionable, adjunctive, and patient-centred.
Actionable targets include clinical response and remission, normalisation of C-reactive protein (CRP), reduction of faecal calprotectin to an acceptable threshold, and endoscopic remission.
Failure to achieve these targets after adequate treatment optimisation should generally prompt consideration of switching treatment or adding a therapy with a different mechanism of action.
Adjunctive targets include bowel urgency, histological remission in ulcerative colitis, transmural remission in Crohn’s disease, and normal growth in children.
Although achieving these targets is associated with favourable outcomes, the researchers said there was insufficient evidence from treat-to-target trials to justify switching therapies solely because they had not been achieved.
The third category covers patient-centred outcomes, including fatigue, disability, and quality of life, which should be assessed independently of inflammatory activity.
“This framework aligns the strength of clinical recommendations with the strength of available evidence while accommodating the increasing complexity of personalised medicine in IBD,” the researchers wrote.
They warned that pursuing increasingly stringent remission targets could expose patients to unnecessary treatment changes, adverse effects, and additional costs without necessarily improving outcomes.
“STRIDE-III distinguishes targets that should prompt treatment change from those that primarily guide optimisation and monitoring, while establishing a separate patient-centred pathway based on shared decision-making,” the researchers wrote.
“This framework supports consistent, evidence-based treat-to-target care.”
The recommendations also establish clearer biochemical targets for both Crohn’s disease and ulcerative colitis.
A faecal calprotectin level below 200μg/g was considered an acceptable target for low inflammatory activity, while levels below 100μg/g were associated with deeper remission, including transmural remission in Crohn’s disease and histological remission in ulcerative colitis.
Values between 100μg/g and 200μg/g represented a grey zone requiring individualised interpretation.
The researchers cautioned against making treatment decisions based on a single faecal calprotectin measurement because of variability between tests and the influence of factors unrelated to IBD.
Instead, serial measurements should be interpreted alongside symptoms, disease phenotype, treatment response, and other objective measures.
Persistent levels above 200μg/g after sufficient treatment time and adequate optimisation should prompt reassessment of the treatment strategy.
STRIDE-III also establishes more explicit timelines for assessing treatment response.
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Clinical improvement should generally be evident within one to two months, with clinical remission expected within two to three months, depending on the treatment used.
Normalisation of CRP and reduction of faecal calprotectin to target levels were intermediate goals, generally assessed at four to six months.
Endoscopic remission remained the principal long-term objective, typically assessed at seven to 12 months.
For Crohn’s disease, endoscopic remission was defined as a Simplified Endoscopic Score for Crohn’s Disease (SES-CD) of two or less, with a score of one or less representing a more stringent goal.
For ulcerative colitis, the preferred target was a Mayo endoscopic subscore of zero.
However, the researchers acknowledged that patients with limited residual inflammation and otherwise well-controlled disease might reasonably continue their existing therapy with close monitoring.
The recommendations also addressed growing interest in achieving deeper levels of remission.
In ulcerative colitis, histological remission was associated with reduced risks of relapse and colectomy, but evidence that escalating treatment to achieve histological remission provided additional benefit beyond complete endoscopic remission remained inconsistent.
The researchers highlighted findings from the VERDICT trial, which demonstrated that targeting combined endoscopic and histological remission reduced ulcerative colitis-related complications compared with targeting symptomatic remission alone, but not compared with endoscopic remission alone.
“Taken together, histological remission is presented as an adjunctive target to consider in treatment optimisation with other disease variables, most notably complete endoscopic remission,” they wrote.
Similarly, transmural remission in Crohn’s disease was associated with favourable long-term outcomes, but there was insufficient interventional evidence to support changing therapies solely to achieve it.
The recommendations recognised the increasing role of intestinal ultrasound (IUS) in monitoring treatment response, particularly in Crohn’s disease, where it offers a non-invasive method of assessing bowel wall inflammation.
Another significant development was the formal recognition of fatigue, disability, and quality of life as long-term patient-centred treatment targets. The researchers reported that disability affected about 30–50% of patients with IBD and could persist even in clinical remission.
Fatigue was also common, affecting between 24% and 87% of children and adults across studies, and may continue despite adequate inflammatory control.
The recommendations called for routine assessment of these outcomes, including investigation of nutritional deficiencies, sleep disturbance, psychological factors, and treatment-related adverse effects.
Persistent fatigue despite deep remission should prompt multidisciplinary assessment rather than automatic escalation of anti-inflammatory treatment.
The updated recommendations have implications for Australian gastroenterologists balancing the benefits of advanced therapies against treatment burden, monitoring requirements, and the risks of unnecessary switching.
The distinction between actionable and adjunctive targets offers a framework for deciding when persistent inflammatory findings justify changing treatment and when optimising an existing regimen may be more appropriate.
The researchers also acknowledged that access to biomarkers, imaging, endoscopy, and advanced therapies varied considerably between healthcare settings.
They recommended maintaining the same therapeutic goals in resource-limited environments while adapting monitoring strategies to the investigations available.
“As the evidence base evolves, future iterations of STRIDE could incorporate more complex longitudinal and multidomain approaches that move beyond categorical target attainment,” the researchers concluded.
“Emerging artificial intelligence (AI) tools might enable the integration of these multimodal patient-specific data to improve individualised risk prediction and treatment selection.
“Emerging multi-omics-based biomarkers could facilitate the assessment of molecular remission as a treatment target.
“Priorities include predicting disease course and response, defining biological endotypes, and validating AI-supported decision tools.
“STRIDE-III should therefore be viewed as an adaptable framework rather than a final definition of care.
“By distinguishing actionable targets from prognostic and complementary measures, STRIDE-III allows new evidence to be incorporated while preserving the flexibility required for individualised decisions.”
