Crohn's disease medical therapy

Crohn's disease
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]

Overiew

Treatment options include medications, nutrition supplements, surgery, or a combination of these options. The goals of treatment are to control inflammation, correct nutritional deficiencies, and relieve symptoms like abdominal pain, diarrhea, and rectal bleeding. Treatment for Crohn’s disease depends on the location and severity of disease, complications, and the person’s response to previous medical treatments when treated for recurring symptoms. Some people have long periods of remission, sometimes years, when they are free of symptoms. However, the disease usually recurs at various times over a person’s lifetime.

Medical Therapy

The first step in the management of an acute Crohn's disease attack involves determining the anatomical extent of the disease endoscopically, and the severity of the disease, clinically. This classification is important to determine the necessity for topical (in distal disease) or systemic (in extensive disease) pharmacotherapy. Additionally, the severity of the disease may help determine the prognosis and the requirement for more aggressive intervention. Once the disease goes into remission, the goal of maintenance therapy is to prevent any subsequent acute exacerbations.

• Standard treatment for Crohn's disease depends on extent of involvement and disease severity (e.g. mild, moderate, severe and fulminant) and can be discussed as follows:

• 1. Mild to Moderate Crohn's Disease
  • Ileitis and colitis
    • Preferred regimen for illeitis and rt side colitis: Oral budesonide (9 mg/day)
    • Preferred regimen distal colitis : Topical mesalamine or topical steroids (enemas or suppositories)
    • Preferred regimen other site :Oral mesalamine (4 g/day) or oral sulfasalazine (3-6 g/day)
    • Alternative regimen (1): Mesalamine enemas or suppositories (in patients refractory to topical corticosteroids or oral aminosalicylates.
    • Alternate regimen (2): Oral prednisone up to 40-60 mg/day AND infliximab 5mg/kg at weeks 0, 2, 6 of treatment
      • Note: Effective dose of Sulfasalazine is 4-6g/day in 4 doses; mesalamine is 2-4.6g/day in 3 doses; balasalazine 6.75g/day in 3 doses; mesalamine multimatrix formulation is 2.4 to 4.8 g/day. These drugs are effective within 2.4 weeks.
  • Oral lesion

• • Preferred regimen (1): triamcinolone acetonide
  • Preferred regimen (2): mesalamine suppository 500 mg qd or bid
  • Preferred regimen (3):mesalamine enema 2-4 g q1-3 days
  • Preferred regimen (4):sulfasalazine 2g/day OR mesalamine compounds 1.6g/day OR balsalazide 3-6g/day
  • Alternative regimen (1): 6-mercaptopurine OR azathioprine AND infliximab
    • Note: A combination of oral mesalamine 1.6g/day and mesalamine enema 4g twice weekly is more effective than oral treatment alone.
• Gastroduodenal disease
  • Preferred regimen (1): PPI or H2 antagonist, or sucralfate
  • Preferred regimen (2): Oral mesalamine (Pentasa: 2 g/day)
• Maintaince therapy
  • Preferred regimen for proctitis: Mesalamine suppositories
  • Preferred regimen for distal colitis : Mesalamine enemas
  • Preferred regimen for others: Oral sulfasalazine or olsalazine or mesalamine(3-3.6 g/day) or balsalazide

• 2. Management of Moderate to Severe Crohn's Disease
  • Acute Management
    • Preferred regimen (1): Oral steroids (in patients refractory to aminosalicylates in combination with topical therapy)
    • Alternate regimen (2): Methotrexate (25 mg/wk i.m and once improvement 15 mg/wk i.m or oral or s.c) (in patients refractory to oral steroids)
    • Alternative regimen (3): infliximab 5mg/kg I.V. at weeks 0,2, and 6 (steroid refractory or steroid dependent despite adequate 6-MP dosing or intolerant to other regimens)
    • Alternative regimen (4): Adalimumab (160 mg s.c at 0 wk and 80 mg/2 wks)
    • Alternative regimen (5): Certolizumab pegol (400 mg/4wk s.c)
    • Alternative regimen (6): Azathioprine (2-3 mg/kg/day) OR 6-mercaptopurine (1-1.5 mg/kg/day)
      • Note (1): Infliximab is contraindicated in patients with untreated latent TB, pre-existing demyelinating disorder, optic neuritis, moderate to severe CHF, current or recent malignancy
      • Note (2): Transdermal nicotine is effective in achieving remission.

• Maintenance of Remission
  • Preferred regimen (1): 6-mercaptopurine (1.5 mg/kg) OR azathioprine (2-2.5 mg/kg)
  • Alternate regimen (2): infliximab (in patients with successful induction with infliximab)
  • Alternate regimen (3): infliximab and azathioprine therapy
  • Alternate regimen (4): Methotrexate therapy (15 mg/wk i.m) (For methotrexate induced remissions)
  • Alternate regimen (5): Adalimumab therapy (40 mg/wk s.c): For adalimumab induced remissions
  • Alternate regimen (6): Certolizumab pegol therapy (400 mg/ 4wk s.c): For certolizumab pegol induced remissions
  • Alternate regimen (7): Natalizumab therapy (300 mg/ 4wk s.c): For natalizumab induced remissions
    • Note (1) : Corticosteroids are not recommended for long-term maintenance therapy
    • Note (2) : Monitor CBC every 3 months, monitor periodically for side effects

• 3.Management of Severe to Fulminant Crohn's Disease

• • Acute Management
    • Preferred Regimen (1): Maximal oral treatment with prednisone AND oral aminosalicylate drugs AND topical mesalamine
    • Alternate regimen (2): Infliximab 5mg/kg (if refractory and urgent hospitalization is not necessary)
    • Alternate regimen (3): Intravenous corticosteroids (if patient presents with toxicity)
      • Note: Failure to show significant improvement within 3-5 days is an indication for colectomy. Infliximab may be effective in avoiding colectomy in patients failing to respond to corticosteroids.

• • Maintenance of Remission
    • Preferred Regimen (1): 6 mercaptopurine

Pharmacotherapy

Aminosalicylates

Sulfasalazine has been a major agent in the therapy of mild to moderate UC for over 50 years. In 1977 Mastan S.Kalsi et al determined that 5-aminosalicyclic acid (5-ASA and mesalazine) was the therapeutically active compound in sulfasalazine. Since then many 5-ASA compounds have been developed with the aim of maintaining efficacy but reducing the common side effects associated with the sulfapyridine moiety in sulfasalazine.

• Mesalazine, also known as 5-aminosalicylic acid, 5-ASA, Asacol, Pentasa and Mesalamine.
• Sulfasalazine, also known as Azulfidine.
• Balsalazide, also known as Colazal.
• Olsalazine, also known as Dipentum.

Corticosteroids

• Cortisone
• Prednisone
• Prednisolone
• Hydrocortisone
• Methylprednisolone
• Beclometasone
• Budesonide

Immunosuppressive drugs

• Mercaptopurine, also known as 6-Mercaptopurine, 6-MP and Purinethol.
• Azathioprine, also known as Imuran, Azasan or Azamun, which metabolizes to 6-MP.
• Methotrexate, which inhibits folic acid
• Tacrolimus

Biological treatment

• Infliximab
• Visilizumab

Contraindicated medications

Crohn's disease is considered an absolute contraindication to the use of the following medications:

• Alosetron