Crohn's Disease Evaluation and Treatment
Initial Diagnostic Approach
For patients with suspected Crohn's disease, confirm diagnosis through endoscopy with biopsies demonstrating focal, asymmetric, transmural or granulomatous features, combined with cross-sectional imaging (CT or MR enterography) to assess disease extent and complications. 1
Key Diagnostic Elements
- Endoscopic evaluation is the gold standard, looking for skip lesions, cobblestoning, and transmural inflammation 1
- CT enterography is the preferred first-line radiologic study for small bowel assessment, though MR enterography has similar accuracy without radiation exposure 1
- Laboratory testing should include inflammatory markers (CRP, ESR) and fecal calprotectin, which has value to rule out disease in adults and children 2
- Disease classification using Montreal criteria: age at diagnosis (<16,17-40, >40), location (ileal, colonic, ileocolonic), and behavior (non-stricturing/non-penetrating, stricturing, penetrating) 1
Treatment Strategy by Disease Severity
Mild to Moderate Disease (Ileal/Right Colonic)
Use budesonide 9 mg/day for induction of remission in patients with mild-to-moderate Crohn's disease limited to the ileum and/or ascending colon. 3
- Budesonide is superior to placebo for inducing clinical response (RR: 1.46,95% CI: 1.03-2.07) and remission (RR: 1.93,95% CI: 1.37-2.73) 3
- Budesonide has significantly fewer systemic side effects than conventional corticosteroids while maintaining similar efficacy 3
- Avoid 5-aminosalicylates (mesalamine) for induction therapy—they show no clear benefit over placebo and are not recommended 3, 4, 5
Mild to Moderate Disease (Colonic Only)
Consider sulfasalazine for patients with disease confined to the colon, though efficacy is modest. 3, 4, 5
- Sulfasalazine shows a trend toward benefit over placebo (45% vs 29% remission, RR 1.38,95% CI 1.00-1.89) specifically in Crohn's colitis 4
- Sulfasalazine is inferior to corticosteroids but has fewer adverse events 4
Moderate to Severe Disease
Use systemic corticosteroids (prednisolone 0.5-0.75 mg/kg/day, maximum 60 mg) for induction of clinical response and remission in moderate-to-severe disease. 3
- Corticosteroids are twice as effective as placebo for inducing remission (RR: 1.99,95% CI: 1.51-2.64) 3
- Taper prednisolone at 5 mg/week over 8-12 weeks 3
- Critical caveat: Corticosteroids should never be used for maintenance therapy due to significant adverse effects including Cushing syndrome, infections, osteoporosis, and growth failure in children 3
Biologic Therapy Indications
First-Line Anti-TNF Therapy
In patients with moderate-to-severe Crohn's disease with risk factors for poor prognosis (stricturing/penetrating disease, perianal disease, young age at diagnosis, extensive disease), initiate anti-TNF therapy (infliximab or adalimumab) as first-line treatment. 3, 6
Infliximab Dosing (FDA-Approved)
- Induction: 5 mg/kg IV at weeks 0,2, and 6 7
- Maintenance: 5 mg/kg IV every 8 weeks 7
- Indicated for reducing signs/symptoms, inducing/maintaining remission, and reducing draining fistulas 7
Adalimumab Dosing (FDA-Approved)
- Adults: 160 mg SC on Day 1 (single dose or split over 2 days), 80 mg on Day 15, then 40 mg every other week starting Day 29 8
- Pediatrics ≥40 kg: Same as adult dosing 8
- Pediatrics 17-40 kg: 80 mg Day 1,40 mg Day 15, then 20 mg every other week 8
Anti-TNF for Conventional Therapy Failures
In patients who fail corticosteroids, thiopurines, or methotrexate, strongly recommend anti-TNF therapy (infliximab or adalimumab) to induce remission. 3
- This is a strong recommendation with high-quality evidence 3
- Evaluate symptomatic response between 8-12 weeks to determine need for therapy modification 3
Combination Therapy Considerations
When starting anti-TNF therapy, consider combining with thiopurine to improve pharmacokinetics and reduce immunogenicity, though avoid thiopurine combinations in young males due to hepatosplenic T-cell lymphoma risk. 3, 8
- Combination therapy may be more effective than monotherapy for inducing remission 3
- Azathioprine and 6-mercaptopurine may be continued during anti-TNF treatment if necessary 8
Maintenance Therapy
After Achieving Remission with Anti-TNF
Continue anti-TNF therapy in patients who achieve symptomatic response with induction therapy to maintain complete remission. 3
- This is a strong recommendation with high-quality evidence 3, 6
- For loss of response, perform dose optimization guided by therapeutic drug monitoring 3
- Do not switch between anti-TNF agents in patients doing well on current therapy 3
Steroid-Dependent Patients
Use thiopurines (azathioprine 2-2.5 mg/kg/day or 6-mercaptopurine 1-1.5 mg/kg/day) for maintenance of remission in steroid-dependent patients. 3
- Strong recommendation with moderate-quality evidence 3
- Do not use thiopurines for induction therapy—they are ineffective for inducing remission 3
- Evaluate response within 12-16 weeks and modify therapy if corticosteroid-free remission not achieved 3
Methotrexate Alternative
Consider parenteral methotrexate (25 mg IM/SC weekly) for steroid-dependent/resistant patients who cannot tolerate thiopurines. 3
- Use for both induction and maintenance in responders 3
- This is a conditional recommendation with very low-quality evidence 3
Second-Line Biologic Therapy
Vedolizumab
In patients who fail anti-TNF therapy, corticosteroids, thiopurines, or methotrexate, use vedolizumab to induce complete remission. 3
- Strong recommendation with moderate-quality evidence for multiple therapy failures 3
- Evaluate symptomatic response between 10-14 weeks 3
- Continue vedolizumab in responders for maintenance therapy 3
Upadacitinib for Refractory Disease
For severe refractory Crohn's disease with documented failure of anti-TNF and thiopurines, consider upadacitinib with dose optimization for loss of response. 9
- Confirm active disease and rule out strictures, abscesses, or surgical complications before re-induction 9
- Monitor response at 6-10 weeks 9
- Be vigilant for herpes zoster infections, particularly at higher doses 9
Pediatric Considerations
Pediatric Induction Therapy
For children 6 years and older with moderate-to-severe Crohn's disease, use anti-TNF biologics (infliximab or adalimumab) for induction and maintenance, particularly at diagnosis or early stages of severe disease. 3
- Strongly recommend against oral 5-aminosalicylates for induction or maintenance in moderate disease 3
- Recommend against thiopurines for induction therapy 3
- Recommend against corticosteroids for maintenance therapy 3
- Recommend against cannabis in any role 3
Exclusive Enteral Nutrition
Consider exclusive enteral nutrition (EEN) as an alternative induction therapy in pediatric patients. 3
- This avoids corticosteroid side effects including growth suppression 3
- Particularly valuable in children where growth is a concern 3
Monitoring and Treatment Targets
Mucosal Healing Assessment
Assess patients in clinical remission receiving immunomodulators for mucosal healing within 1 year of treatment initiation. 3
- Endoscopic healing is the gold standard for measuring disease activity 1
- Treatment should target endoscopic healing, not just symptom resolution 1, 10
Therapeutic Drug Monitoring
Use therapeutic drug monitoring to guide dose optimization in patients losing response to anti-TNF therapy. 3
- This helps distinguish between low drug levels and true treatment failure 3
- Note that therapeutic drug monitoring is not established for newer agents like upadacitinib 9
Critical Pitfalls to Avoid
- Never use 5-aminosalicylates for moderate-to-severe disease—they lack efficacy and delay appropriate treatment 3, 4
- Never use corticosteroids for maintenance therapy—they cause significant morbidity without preventing relapse 3
- Never delay anti-TNF therapy in high-risk phenotypes (stricturing, penetrating, perianal disease)—this leads to irreversible complications 6
- Never use thiopurines for induction—onset of action is too slow (12-16 weeks) 3
- Avoid thiopurine combinations in young males due to hepatosplenic T-cell lymphoma risk 3, 8
Surgical Considerations
Recognize that surgery remains necessary in up to two-thirds of patients during their lifetime, with indications including medically refractory disease, perforation, obstruction, abscess not amenable to drainage, and intractable hemorrhage. 1