Ulcerative colitis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tarek Nafee, M.D. [2]

Overview

The first step in the management of an acute ulcerative colitis 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.

Medical Therapy

The goal of medical therapy is to induce remission initially with medications, followed by the administration of maintenance medications to prevent a relapse of the disease. The concept of induction of remission and maintenance of remission is very important. The medications used to induce and maintain a remission somewhat overlap, but the treatments are different. Physicians first direct treatment to inducing a remission which involves relief of symptoms and mucosal healing of the lining of the colon and then longer term treatment to maintain the remission.

Standard treatment for ulcerative colitis depends on extent of involvement (proximal vs. distal) and disease severity (e.g. mild, moderate, severe and fulminant) as follows:

• 1. Mild to Moderate Distal Colitis
  • Acute Management
    • Preferred regimen (1): Topical Mesalamine
    • Preferred regimen (2): Topical corticosteroids
    • Preferred regimen (3):Oral aminosalicylates
    • 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.

• Maintenance of Remission
  • Preferred regimen (1): mesalamine suppository 500 mg qd or bid
  • Preferred regimen (2):mesalamine enema 2-4 g q1-3 days
  • Preferred regimen (3):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.

• 2. Mild to Moderate Extensive Colitis
  • Acute Management
    • Preferred regimen (1): oral sulfasalazine titrated up to 4-6g/day OR oral aminosalicylate in doses of up to 4.8g/day of active 5-ASA moiety
    • Alternate regimen (1): Oral steroids (in patients refractory to aminosalicylates in combination with topical therapy)
    • Alternate regimen (2): 6-mercaptopurine AND azathioprine (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)
      • 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): Sulfasalazine, olsalazine, mesalamine, and balsalazide
  • Alternative regimen (1): 6-mercaptopurine OR azathioprine
  • Alternate regimen (2): infliximab (in patients with successful induction with infliximab)
    • Note: Corticosteroids are not recommended for long-term maintenance therapy

• 3.Severe Colitis

• • 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

• 4.Management of Pouchitis (complication of IPAA surgery)

• • Preferred Regimen (1): Metronidazole 400mg q8h OR 20mg/kg daily
  • Preferred Regimen (2): Ciprofloxacin 500mg bid
    • Note: Other etiologies mimicking pouchitis include irritable pouch syndrome, cuffitis, CD of the pouch, and postoperative complications such as anastomotic leak or stricture.

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

Ulcerative colitis is considered an absolute contraindication to the use of the following medications:

• Alosetron
• Dicyclomine
• Glycopyrrolate
• Hyoscyamine
• Methscopolamine bromide
• Loperamide
• Reserpine
• Streptokinase