From the Guidelines
Management of Crohn's disease exacerbation requires prompt intervention with a step-up approach based on disease severity, with the most recent and highest quality evidence suggesting the use of anti-TNF therapy, such as infliximab or adalimumab, as first-line therapy for moderate to severe luminal Crohn's disease with risk factors of poor prognosis 1.
Disease Severity Assessment
The assessment of disease severity should be based on a combination of symptoms, objective measures of inflammation, and factors that predict an increased risk of complications 1.
Treatment Options
For mild to moderate flares, oral corticosteroids such as prednisone 40mg daily with a 4-8 week taper may be recommended as first-line therapy, while budesonide 9mg daily for 8-12 weeks may be preferred for ileal or right-sided colonic disease due to fewer systemic side effects 1.
- Oral corticosteroids:
- Prednisone 40mg daily with a 4-8 week taper
- Budesonide 9mg daily for 8-12 weeks
- Biologics:
- Infliximab (5mg/kg at weeks 0,2, and 6, then every 8 weeks)
- Adalimumab (160mg initially, 80mg at week 2, then 40mg every 2 weeks)
- Ustekinumab (induction with weight-based IV dose, then 90mg subcutaneously every 8 weeks)
Severe Exacerbations
For severe exacerbations, hospitalization for IV corticosteroids (methylprednisolone 40-60mg daily), bowel rest, IV fluids, and consideration of IV biologics may be necessary 1.
Maintenance Therapy
Concurrent optimization of maintenance therapy is essential, which may include increasing doses of immunomodulators like azathioprine (2-3mg/kg/day) or 6-mercaptopurine (1-1.5mg/kg/day) 1.
Antibiotics and Surgical Consultation
Antibiotics like ciprofloxacin 500mg twice daily and metronidazole 500mg three times daily may be added if infection is suspected or for perianal disease, and surgical consultation should be obtained for complications such as obstruction, perforation, or abscess 1.
From the FDA Drug Label
Crohn’s Disease (CD) (1.5): treatment of moderately to severely active Crohn’s disease in adults and pediatric patients 6 years of age and older.
The management of Crohn's disease exacerbation with adalimumab (SQ) involves treating moderately to severely active Crohn's disease in adults and pediatric patients 6 years of age and older.
- Key points:
- Adalimumab is indicated for the treatment of moderately to severely active Crohn's disease.
- The dosage for Crohn's disease is as follows:
- Adults: 160 mg on Day 1 (given in one day or split over two consecutive days); 80 mg on Day 15; and 40 mg every other week starting on Day 29.
- Pediatric Patients 6 Years of Age and Older:
- 17 kg (37 lbs) to less than 40 kg (88 lbs): Day 1: 80 mg, Day 15: 40 mg, and 20 mg every other week starting on Day 29.
- 40 kg (88 lbs) and greater: Day 1: 160 mg (single dose or split over two consecutive days), Day 15: 80 mg, and 40 mg every other week starting on Day 29.
From the Research
Management of Crohn's Disease Exacerbation
- The management of Crohn's disease exacerbation involves a range of therapeutic options, including 5-aminosalicylates, thiopurines, methotrexate, and infliximab 3.
- First-line therapy for Crohn's disease exacerbation generally consists of steroids for rapid palliation of symptoms during initiation of anti-tumor necrosis factor α therapy 4.
- Azathioprine and 6-mercaptopurine are effective in chronic active disease and corticosteroid-dependent Crohn's disease, and may allow patients to reduce steroid consumption 5.
- Infliximab has been shown to be effective in inducing remission and delaying relapse in patients with Crohn's disease 3, 4.
- The combination of azathioprine and infliximab may be superior to infliximab alone for induction of steroid-free clinical remission 5.
Maintenance of Remission
- Azathioprine is significantly superior to placebo for maintenance of remission in quiescent Crohn's disease 6.
- Azathioprine may be superior to budesonide for maintenance of remission, but the evidence is limited by small study size and high risk of bias 6.
- Purine analogues may be superior to placebo for maintenance of surgically-induced remission in patients with Crohn's disease, although the evidence is based on small studies 7.
- Adalimumab may be superior to azathioprine for maintenance of remission, but further research is needed to confirm these results 7.
Adverse Events
- Azathioprine and 6-mercaptopurine are associated with adverse events, including leukopenia, pancreatitis, nausea, and allergic reactions 5, 6, 7.
- Patients taking purine analogues are more likely to discontinue therapy due to adverse events compared to those taking 5-ASA agents 7.
- Commonly reported adverse events across all studies include leucopenia, arthralgia, abdominal pain, elevated liver enzymes, nausea, and vomiting 7.