Practical Summary of 2025 ACG Guidelines for Crohn's Disease

Crohn's Disease in Adults: 2025 ACG Evidence-Based Guidelines
Crohn's disease (CD) remains one of the most challenging inflammatory bowel diseases (IBD) for gastroenterologists to manage, due to its unpredictable course, heterogeneity of presentation, and complex therapeutic landscape. The American College of Gastroenterology (ACG) has updated its clinical guidelines for 2025, reflecting advances in diagnostic strategies, risk stratification, medical therapy, monitoring, and surgical interventions. These guidelines aim to refine clinical decision-making, optimize patient outcomes, and reduce complications.



Below is an in-depth exploration of the 2025 ACG Clinical Guidelines for the Management of Crohn Disease in Adults, designed for practicing physicians, gastroenterology trainees, IBD specialists, and allied healthcare professionals.

Epidemiology and Burden of Disease
Crohn's disease is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, most commonly affecting young adults. The prevalence is rising globally, with significant increases noted in Asia, the Middle East, and Latin America, mirroring Western epidemiology.

• Onset and demographics: Peak incidence occurs between ages 15 and 35, with a smaller peak later in life.
  
  
• Economic burden: Hospitalizations, surgeries, and biologic therapy constitute the largest drivers of healthcare costs.
  
  
• Quality of life impact: Beyond intestinal inflammation, fatigue, malnutrition, extraintestinal manifestations, and psychosocial distress, these conditions impose a heavy burden on patients.
  

Diagnostic Principles
The 2025 ACG guidelines emphasize a multimodal diagnostic strategy that combines clinical suspicion, endoscopy, imaging, and histopathology.

Clinical Assessment

• Chronic diarrhea, abdominal pain, weight loss, and fatigue remain key clinical markers.
  
  
• Alarm features such as perianal disease, penetrating complications, and anemia should trigger expedited evaluation.
  

Endoscopy

• Ileocolonoscopy with segmental biopsies remains the gold standard.
  
  
• Guidelines emphasize detailed mucosal mapping to assess the extent, distribution, and severity.
  
  
• Video capsule endoscopy is reserved for cases with high suspicion and negative ileocolonoscopy.
  

Imaging

• Cross-sectional imaging (MR enterography or CT enterography) is strongly recommended for evaluating small-bowel disease and extramural complications such as fistulas and abscesses.
  

Histopathology

• Non-caseating granulomas, transmural inflammation, and architectural distortion support the diagnosis.
  
  
• ACG stresses that histology alone is not diagnostic and must be integrated with clinical and radiologic data.
  

Risk Stratification and Prognosis
The updated guidelines stress early risk stratification to personalize treatment intensity.

High-risk features include:

• Diagnosis before age 30
  
  
• Extensive small-bowel involvement
  
  
• Perianal or penetrating disease at diagnosis
  
  
• Deep ulcers on endoscopy
  
  
• Prior need for steroids or hospitalization
  

Patients with high-risk disease should be considered for early initiation of advanced therapy (biologics or small molecules) rather than traditional step-up strategies.



Treatment Strategies
The 2025 ACG guidelines classify management into induction of remission and maintenance of remission, emphasizing treat-to-target approaches.

Corticosteroids

• Effective for short-term induction, but not recommended for maintenance.
  
  
• Budesonide remains an option for mild-to-moderate ileocecal disease.
  

Immunomodulators

• Thiopurines (azathioprine, 6-MP): declining use due to adverse effect profile and modest efficacy.
  
  
• Methotrexate: still recommended as an option in steroid-dependent patients intolerant to thiopurines.
  

Biologics
Biologics remain the cornerstone of moderate-to-severe Crohn disease management.

1. Anti-TNF agents (infliximab, adalimumab, certolizumab pegol)
   
   • Strong recommendation for induction and maintenance in moderate-to-severe CD.
     
     
   • Early combination with immunomodulators may enhance efficacy.
     
2. Anti-integrin therapy (vedolizumab)
   
   • Preferred in patients with higher infection risks or contraindications to systemic immunosuppression.
     
     
   • Demonstrated safety advantage, particularly in older adults.
     
3. Anti-IL-12/23 (ustekinumab) and Anti-IL-23 selective agents (risankizumab)
   
   • Highly effective in both induction and maintenance.
     
     
   • Guidelines highlight risankizumab’s role as a frontline biologic in high-risk patients.
     
4. JAK inhibitors (upadacitinib)
   
   • Now incorporated into ACG’s algorithm as an oral small-molecule therapy for patients failing biologics.
     
     
   • Boxed warnings regarding infection and cardiovascular risk necessitate careful patient selection.
     

Combination Therapy

• Biologic plus immunomodulator therapy may reduce immunogenicity and enhance remission rates.
  
  
• However, the risk of infection and malignancy requires shared decision-making.
  

Treat-to-Target Approach
Borrowing from the STRIDE-II consensus, the 2025 guidelines recommend tight disease monitoring and proactive therapy adjustments.

Targets include:

• Short-term: Clinical remission (resolution of symptoms, normalization of CRP/fecal calprotectin).
  
  
• Intermediate-term: Endoscopic healing (absence of ulcers).
  
  
• Long-term: Prevention of disability, surgery, and colorectal cancer.
  

Monitoring is recommended at 3–6 month intervals using biomarkers, endoscopy, and imaging.

Surgical Management
Despite therapeutic advances, up to 50% of patients require surgery within 10 years.

Indications include:

• Intestinal obstruction or strictures
  
  
• Perforation, abscess, or fistula not controlled medically
  
  
• Medically refractory disease
  
  
• Dysplasia or malignancy
  

Strictureplasty remains an option for small-bowel strictures, while segmental resection is used for localized disease. The guidelines emphasize early surgical referral as part of multidisciplinary care.

Special Populations
Perianal Crohn Disease

• Anti-TNF therapy remains first-line.
  
  
• Combination with seton placement, antibiotics, and surgical drainage is recommended.
  

Elderly Patients

• Vedolizumab and ustekinumab are favored for better safety profiles.
  
  
• Immunomodulators are discouraged due to higher malignancy risk.
  

Pregnancy

• Biologics, especially anti-TNF, vedolizumab, and ustekinumab, are generally safe.
  
  
• Methotrexate remains contraindicated.
  
  
• Multidisciplinary care is essential for maternal and fetal outcomes.
  

Extraintestinal Manifestations

• Joint, skin, ocular, and hepatobiliary involvement requires tailored therapy.
  
  
• Biologics targeting systemic inflammation (anti-TNF, ustekinumab) are preferred.
  

Nutrition and Lifestyle
The guidelines strongly endorse nutritional assessment and adjunct dietary therapy.

• Exclusive enteral nutrition (EEN): effective for pediatric induction, less used in adults.
  
  
• Partial enteral nutrition and Crohn’s disease exclusion diets: emerging adjuncts with promising results.
  
  
• Micronutrient monitoring: Vitamin D, B12, iron, and folate must be regularly assessed.
  

Lifestyle modifications emphasized:

• Smoking cessation: the strongest modifiable risk factor for relapse and surgery.
  
  
• Exercise and stress reduction: improve quality of life and reduce fatigue.
  

Cancer Surveillance
Patients with long-standing Crohn colitis face elevated colorectal cancer risk.

• Colonoscopic surveillance is recommended every 1–3 years based on risk factors (extent, duration, family history, PSC).
  
  
• Chromoendoscopy is preferred for detecting dysplasia.
  

Health System and Cost Considerations
The 2025 ACG guidelines address value-based care, noting that biologics and small molecules impose significant financial strain. Cost-effectiveness analyses support early advanced therapy in high-risk patients to reduce hospitalizations and surgeries.

Future Directions
The guidelines highlight evolving frontiers in Crohn disease care:

• Precision medicine: Biomarker-guided biologic selection.
  
  
• Microbiome therapies: Fecal microbiota transplantation under investigation.
  
  
• Novel small molecules: TYK2 inhibitors and sphingosine-1-phosphate modulators.
  
  
• Digital health monitoring: Wearable devices, home calprotectin testing, and telemedicine to enhance proactive care.