In the management of Crohn’s disease, a key objective — preserving the bowel by reducing the need for multiple resections — is gaining ground. Advances in treat-to-target (T2T) and perioperative strategies are providing increasing opportunities to tackle the disease with precision and improve chances for remission.

“In this rapidly advancing field, innovation is measured not only by clinical outcomes but also by every centimeter of bowel preserved,” wrote the authors of a review published recently in the Journal of Crohn’s and Colitis.

“The therapeutic paradigm of treat-to-target and tight disease monitoring is shifting the focus from reactive interventions to proactive and personalized care,” they added.

Crohn’s disease, in the family of chronic inflammatory bowel diseases (IBDs), commonly involves the development of complications such as abscesses and fistulas, which result in eventual resective surgery in at least a third of patients — with relapses and multiple surgeries common.

Those repeated surgeries can increase the risk for short bowel syndrome, and the possible need for lifelong parenteral nutrition and/or intestinal transplantation, hence bowel preservation is a critical priority.

Biologics Paving the Way to Higher Remission

Among the most important developments in recent years helping to reduce resection rates has been the advent of biologic agents, such as anti-TNF drugs. These include infliximab, adalimumab, and certolizumab pegol; anti-integrin agents, including vedolizumab, and more recently, selective monoclonal antibodies including ustekinumab, as alternatives to conventional therapies, such as corticosteroids.

“The most promising strategy [for bowel preservation] is to treat Crohn’s disease early, right after the diagnosis, with effective medical therapy, such as biologics or small molecules,” Paulo Gustavo Kotze, MD, PhD, of the IBD Outpatient Clinics — Colorectal Surgery Unit, at Catholic University of Paraná, in Curitiba, Brazil, told Medscape Medical News. Kotze was the first author of the review mentioned above.

Among research detailing the benefits of the shift toward biologics is a recent study of data from 26 major US healthcare centers, showing that patients with Crohn’s disease treated with biologics at least 60 days before undergoing intestinal resection had a 26% lower chance of having intestinal resection than those never treated with biologics (odds ratio [OR], 0.74; P < .001).

The results suggest that “biologic therapy in IBD may alter the natural course of the disease and impact the need for surgery,” the authors reported. “Patients treated earlier in their disease course may require less surgery than those treated later.”

Further research showed the use of prophylaxis with biologics to be associated with a reduced risk for surgical recurrence after resection, regardless of patients’ risk for recurrence.

In terms of the best therapy choices in that context, Benjamin H. Click, MD, a co-author on both studies, told Medscape Medical News that “real-world studies comparing advanced therapies have not consistently shown that any one therapy is superior to another.”

More important is that “any advanced therapy is likely better than no therapy, especially for individuals at high risk of disease recurrence,” said Click, an associate professor of Medicine in the Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado.

Drug Combinations

Among key caveats of biologics is evidence suggesting a plateauing of their benefits, described in one recent meta-analysis that showed no clear change in clinical outcomes over the years.

Strategies to lift that therapeutic ceiling include the use of drug combinations, which are increasingly showing improved results.

In the recent EXPLORER trial, for instance, benefits were observed with a triple combination of two biologics with distinct mechanisms of action: adalimumab, an anti-TNF-alpha treatment, and vedolizumab, a gut-selective biologic, along with the immunomodulator methotrexate, in endoscopic remission after 26 weeks, with no additional safety concerns relative to monotherapy.

Further evidence of synergistic benefits resulting from dual therapy with the biologics ustekinumab and vedolizumab was shown in another recent study, which showed improved safety and efficacy of the two-drug combination over monotherapy in inducing disease remission in refractory Crohn’s disease.

T2T and Tight Control

Further enhancing the therapeutic benefit of biologics is the use of the proactive T2T approach, which involves measures including endoscopic healing and monitoring inflammatory biomarkers — such as fecal calprotectin — to guide postoperative treatment escalation, rather than relying only on clinical symptoms.

Such measures are considered much more accurate indicators of disease remission than clinical symptoms alone as up to 50% of patients in remission based solely on clinical symptoms can have underlying inflammation.

In this context, recent data support the use of noninvasive, intestinal ultrasound to detect postoperative disease activity, while therapeutic drug monitoring is also gaining recognition, with some studies suggesting that higher trough concentrations and lower anti-drug antibody titers may be associated with a reduced risk for endoscopic recurrence.

“While routine implementation of therapeutic drug monitoring in the postoperative setting requires further validation, this proactive approach may help avoid subtherapeutic exposure, reduce unnecessary dose escalation, and guide more precise therapeutic adjustments,” Kotze and his colleagues noted.

AI Offering Further Refinement

Advances that could help improve upon T2T efforts include the use of deep learning AI, which is being utilized in the assessment of highly complex data in research on genetic predispositions, microbiome profiles, and inflammatory phenotypes for highly individualized patient management and earlier-than-ever outcome predictions.

One recent study, using a deep learning model, integrated endoscopic images and clinical data for the early prediction of secondary loss of response after infliximab treatment in Crohn’s disease.

Other research, published in Scientific Reports, describes utilizing deep learning to forecast remission and response to vedolizumab and ustekinumab in the treatment of IBD.

“In this evolving scenario, artificial intelligence and machine learning could play a crucial role by integrating complex multi-omics data, improving predictive modelling and tailoring both clinical and surgical interventions,” Kotze and colleagues wrote.

A key consideration driving such advances is that “postoperative disease activity typically does not cause symptoms early and requires objective monitoring,” Click noted.

“Regardless of whether or not someone receives postoperative medical prophylaxis, a close monitoring plan in the first year including biomarkers, endoscopic assessments, typically within 6-12 months of surgery, and intestinal ultrasound, when available, should be employed to detect disease activity and direct treatment changes accordingly,” he said.

Challenges in Implementation

Importantly, some of those measures are indeed not available in certain settings, and studies underscore that some factors, such as cost and accessibility, can make adoption of T2T and tight monitoring a challenge.

“Effective and early treatment for our patients is not widely available at a global level,” Kotze told Medscape Medical News. “Obstacles to T2T strategy [include] cost, access to monitoring tests, and effective therapies, and conservative profiles from physicians, who still tolerate residual inflammation. This can be improved.”

Evidence of the lack up uptake of T2T includes one recent large global survey evaluating the real-world practice of T2T approaches. It revealed that only a quarter of respondents reported routinely performing an endoscopy to assess response after starting an advanced therapy.

The findings “highlight the disconnect between clinical practice and many global guidelines,” the study authors noted.

Nurulamin M. Noor, PhD, a clinical lecturer in gastroenterology in the Department of Gastroenterology at Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, who has authored research detailing variation in use of the T2T approach, said better training is needed to improve utilization of the strategy.

“Training and education are important to help increase awareness among clinicians and patients, especially about the risks of ongoing active inflammation and how this can lead to complications arising in the future,” Noor told Medscape Medical News. 

Furthermore, “improving and increasing access to tools such as fecal calprotectin and intestinal ultrasound will likely help ensure greater uptake in the future as these are less cumbersome and more patient-friendly than historic practices such as performing repeated and frequent endoscopies,” Noor said.

Perioperative Advances

In addition to pharmacologic efforts, evidence shows key perioperative strategies can also reduce subsequent surgeries, including exclusive enteral nutrition (EEN), an exclusive liquid diet in the weeks prior to surgery.

Known to have benefits over corticosteroids in maintaining remission in pediatric patients, the approach is gaining favor in adult patients and, as documented in a recent meta-analysis, shows significant reductions in infectious complications.

Further evidence of the role of preoperative EEN in improving bowel preservation is anticipated from the ongoing randomized OCEaN trial.

Likewise, robotic surgical techniques in IBD are helping to improve outcomes of ileocolic resection for Crohn’s disease, as described in a recent meta-analysis. These techniques have shown some longer surgical times, but with the payoff of fewer postoperative complications compared with open surgery and outcomes that are comparable to laparoscopic procedures, with shorter hospital stays. A 2026 study described outcomes in a real-world setting with the use of robotic capsule endoscopy for gastric and enteric evaluation.

Overall, “despite the enhanced disease control that has been achieved in the era of biologics, there are still gaps in the therapeutic management that must be filled,” Kotze and his colleagues wrote in their review.

“In this scenario, the combination of surgical innovations with postoperative prophylaxis and close monitoring is expected to offer increasingly effective options in limiting surgical extension and reducing recurrence,” they added. “A proactive approach guided by personalized predictive models will ensure superior intestinal preservation strategies and enhance patient quality of life.”

Kotze reported consulting and/or lecture fees from AbbVie, Johnson and Johnson, Pfizer, Celltrion, and Takeda. Click reported consulting for Janssen, Takeda, Bristol Myers Squibb, AbbVie, Prometheus, and TARGET-RWE. Noor reported receiving educational/travel grants and/or speaker fees and/or advisory board fees from AbbVie, BMS, Celltrion, Dr Falk, Ferring, Galapagos, J&J, Lilly, Pfizer, Pharmacosmos, Takeda, and Tillotts.